EU Research Summer/Autumn 2016

EU Research Summer 2016

BREXIT: The implications and the future of European Research

Getting beneath the surface of Plasma Materials

Matter of fact: a focus on Solid State Physics Nanoscience in Health

Disseminating the latest research under FP7 and Horizon 2020 Follow EU Research on www.twitter.com/EU_RESEARCH

Editor’s No T he Brexit is dominating every news and social media channel and there is now a big split of opinion that has torn through Britain and divided it in two. The BBC news called it a ‘seismic’ result and it really did feel like a political and cultural earthquake had shaken the foundations of the country.

We are plunged into uncharted waters and of course there will be significant implications for the UK, the EU and science and innovation in both of these soon to be divorced areas. I awoke as did many on that Friday morning when the ballot papers had been counted, with a sense of shock to the news. I did not really believe it would happen but it has happened and it’s time to try and make sense of what directions to take.

As a seasoned editor and journalist, Richard Forsyth has been reporting on numerous aspects of European scientific research for over 10 years.

He has written for many titles including ERCIM’s publication, CSP Today, Sustainable Development magazine, eStrategies magazine and remains a prevalent contributor to the UK business press. He also works in Public Relations for businesses to help them communicate their services effectively to industry and consumers.

Beyond the obvious enormous issue of a possible funding crisis - which British scientists will no doubt be disturbed about, collaboration is one of the real cornerstones of progress in most fields in the EU. I am hoping in the science community we can keep cool heads and collaboration can prevail no matter what politics Europe gets entrenched in, from whichever corner.

The process of the UK disengaging with the EU infrastructure will take a couple of years and this is the first time such a thing has ever happened, so it’s all a stumble through the dark.

It’s most important that the research British scientists are carrying out in healthcare, innovation, technology and scientific exploration is continued as research can benefit everyone. Scientific progress at its best is flag free, unifying, helpful and makes life better for everyone wherever they live and whatever their views. We must take a deep breath, stay positive and see where this path takes us, all of us, within Europe.

Hope you enjoy the issue.

Richard Forsyth Editor

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Contents 31 INTEG-CV-SIM

4 Research News

EU Research takes a look at the latest scientific and research news from around the globe

10 DrugTissueCult Certain bioactive compounds found in plants have anti-cancer properties, now researchers aim to develop new, more sustainable methods of producing them. The DrugTissueCult project aims to find alternative ways to produce the chemicals used in anti-cancer drugs, as Associate Professor Henrik Toft Simonsen explains

12 MOCOMODELS Molybdenum cofactor-dependent enzymes play a central role in many important biological processes.

Professor Carola Schulzke tells us about the work of the MOCOMODELS project in synthesising complexes that mimic the natural molybdenum cofactor of the respective enzymes

15 AEDNET Anthrax remains a significant threat to health in certain parts of the world. The AEDNET project is developing an environmentally-friendly approach to decontamination based on spore biology, work which also holds implications for civil security, as Professor Les Baillie explains

16 CBCD CBCDs can have a severe impact, yet the genetic basis of many of these disorders is still not fully understood. Professor Enza Maria Valente tells us about her work in investigating the basis of these defects, and its wider impact on the prognosis and management of CBCDs

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18 Maladapted

The Maladapted project brings together phenotypic, genetic and demographic evidence to study genomic changes over the period of the last 100,000 years, as Dr Toomas Kivisild and Dr Luca Pagani explain

20 RESPIRE 2 Respiratory diseases remain among the biggest causes of death in Europe, underlining the importance of continued research. The European Respiratory Society funds a wide range of fellowships, including the RESPIRE2 programme, aiming to encourage talented researchers to tackle key challenges in the field, as Professor Maria Belvisi explains

22 GDNF MIMETICS Around 1.2 million Europeans live with Parkinson’s disease, and the disorder is a major research priority. Dr Yulia Sidorova and Dr Mehis Pilv tell us about the GDNF Mimetics project’s work in developing novel disease-modifying treatments against this disease

26 EU Science Funding What dramatic geo-political effects could change everything about the European funding landscape? What if a country joins the EU? What’s the impact of a country leaving the EU? We take a look at how future scenarios could play out for funding

30 ZEYMORPH Relatively little is understood about the underlying molecular mechanisms behind morphogenesis, the process by which our organs are shaped during embryogenesis. The ZEYMORPH project is using advanced imaging and genetic tools to investigate the early stages of eye morphogenesis, as Dr Florencia Cavodeassi explains

Computational modelling of cardiovascular mechanics could greatly enhance surgical planning and help minimise the need for invasive procedures, yet there are limitations to existing techniques.

Professor Alberto Figueroa tells us about his work in developing an integrated computer modelling framework

34 DropCellArray

Cell screening is central to the development of new drugs, yet current methods have some significant limitations. We spoke to Dr Simon Widmaier and Dr Anna Popova about their achievements in Aquarray, a project dedicated to developing a new platform for high-throughput screening experiments on biological cells

36 NANOTRAC The therapeutic potential of nanomedicines has attracted a great deal of interest, yet technical challenges remain before they can be more widely applied in clinical settings. Dr Philipp Seib tells us about NanoTrac’s work in both developing silk-based nanoparticles, and in investigating the body’s response to this form of treatment

37 POMCAPS The physical and chemical properties of a material’s surface have an important influence on how it interacts with the environment.

POMCAPS aims to create macroporous solid materials with wellcontrolled pore morphologies and specific modifications of the pore surfaces, as Principal Investigator Dr Wiebke Drenckhan explains

40 CISS The recent discovery of the CISS Effect marks a new stage in understanding how electrons travel through chiral molecules.

This opens up new possibilities in the application of chiral molecules, and could also lead to new insights into electron transfer processes in biological systems, as Professor Ron Naaman explains

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42 BREXIT The European Union has had the biggest shake up since its conception. The UK, one of the three wealthiest nations in the EU, is divorcing from the relationship. The shockwaves have rippled around the world. We look at how the vote could affect both science and business and what the future may look like

46 CIRQYS CIRQYS is investigating the way light interacts with exotic matter and experimenting with new methodologies and the goal of quantum based technology. Dr Takis Kontos and his team in Paris, are pioneering hybrid circuits which will illuminate the science needed to drive quantum devices

48 DM Dirac Materials Dirac materials are of great interest among researchers, with scientists seeking to make full use of their low-energy electronics properties.

Professor Alexander Balatsky talks about his work in investigating the properties of DMs and searching for ways to modify their functionality

51 PLASMAPOR

Professor Rino Morent tells us about the PLASMAPOR project’s work in using non-thermal atmospheric pressure plasmas to modify the properties of porous materials, research which promises to have a significant impact on science and society

54 PLASMATS Researchers in the PLASMATS project are investigating the use of atmospheric non-thermal plasma technology in their development and functionalization of electrospun nanofibrous mats.

This research holds wider relevance to tissue engineering, as Professor Nathalie De Geyter explains

57 TOPOLECTRICS

Professor Ronny Thomale, the Principal Investigator of the Topolectrics project, tells us about their work in developing a theoretical framework to unify the appearance of topological quantum states of matter

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60 QUSIMGAS Cold gas experiments could act as quantum simulators, creating new insights into many intractable models in condensed matter physics. Professor Lode Pollet talks about the QUSIMGAS project’s work in developing new methods to describe experiments at very low temperatures

62 HYSOL The HYSOL project is developing a new hybrid concept which will combine different sources of energy in a flexible configuration, providing a reliable supply of energy, as Lucia Gonzalez Cuadrado and Alberto R. Rocha explain

64 Solid State Research Some of the more exciting machines we have invented in modern history have been forged with research derived in solid state physics; think particle accelerators, MRI scanners and even floating trains. We look at how we can use studies in this field for advancing efficient energy use and quantum computing

68 SPARCCLE

We spoke to Professor Siddhartha Mishra about the SPARCCLE project’s work in developing a framework that will dramatically increase the range and scope of numerical simulations

70 BEIPD The BeIPD COFUND scheme offers post-doctoral fellows the opportunity to live and perform state-of-the-art research in the heart of Belgium, helping young researchers to build their careers in academia, as project responsible Isabelle Halleux and Raphaela Delahaye, project manager explain

72 ORISTARS

Project Coordinator Dr Philippe André tells us how the ORISTARS project is combining observational, theoretical and instrumental research to gain new insights into how stars form, work which will have significant scientific implications

EDITORIAL Managing Editor Richard Forsyth info@euresearcher.com Deputy Editor Patrick Truss patrick@euresearcher.com Deputy Editor Richard Davey rich@euresearcher.com Science Writer Holly Cave www.hollycave.co.uk Acquisitions Editor Elizabeth Sparks info@euresearcher.com PRODUCTION Production Manager Jenny O’Neill jenny@euresearcher.com Production Assistant Tim Smith info@euresearcher.com Art Director Daniel Hall design@euresearcher.com Design Manager David Patten design@euresearcher.com Illustrator Martin Carr mary@twocatsintheyard.co.uk PUBLISHING Managing Director Edward Taberner etaberner@euresearcher.com Scientific Director Dr Peter Taberner info@euresearcher.com Office Manager Janis Beazley info@euresearcher.com Finance Manager Adrian Hawthorne info@euresearcher.com Account Manager Jane Tareen jane@euresearcher.com

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RESEARCH

NEWS

The EU Research team take a look at current events in the scientific news

New calls to map the world’s oceans The world’s oceans take up approximately two-thirds of the earth’s surface, yet much remains to be learned about the seafloor and the habitats that surround them. The General Bathymetric Chart of the Ocean (GEBCO), a joint project of the International Hydrographic Organisation and the Intergovernment Oceanographic Commission, is now leading calls for a renewed focus on mapping the world’s oceans.

There are still significant gaps in existing maps, despite the long history of ocean surveys, with vast areas of the seas covered by nothing more detailed than a single point. Our relative ignorance of the seafloor has been starkly illustrated by the failure to locate the missing Malaysian airliner MH370, widely believed to have come down somewhere in the southern Indian ocean in March 2014.

Sonar mapping

The plane has still not been located over two years after its disappearance, despite the largest and most expensive multi-national search effort in history. Searchers are using sonar mapping, satellite imagery and other advanced techniques to cover a vast expanse of ocean, yet still the aircraft has not been found.

The relative lack of knowledge about the seafloor has been a factor in these terms, in fact we know more about the moon than we do about our own oceans in some respects. Only around 5 percent of the seafloor has been mapped with modern methods, whereas the entire surface of the moon has been mapped to a

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resolution of 7m, with satellite mapping used to build a detailed picture.

Researchers are now calling for investment to rectify this seeming anomaly, where more is known about the surface of the moon than the surface of our own planet. While mapping the sea floor is a major technical challenge, calling for sophisticated equipment and advanced expertise, experts believe it could be achieved for approximately $3 billion.

This is on a roughly similar scale to the sum required for a single Mars mission, yet ocean-mapping remains a relatively neglected area. GEBCO is now working to bring the issue to wider attention; the Forum for Future Ocean Floor Mapping was held in Monaco between 15-17 June, with keynote speakers including Dr Robert Ballard, who discovered the wreck of the Titanic in 1985.

Undersea mapping

This kind of work tends to attract a great deal of attention, yet undersea mapping is also central to our understanding of other major questions, including those around tsunamis, undersea resource extraction and the global impact of climate change. David Heydon, the founder of submarine mining company Nautilus Minerals, is a firm supporter of further research in this area; “The land we live on is one-third of the planet – it’s rare. The other two-thirds are more than 3,000 metres under the water. It’d be crazy not to understand it,” he stressed.

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Juno probe approaches Jupiter The Juno probe is set to pass close to Jupiter early in July, some five years after it was launched from Cape Canaveral.

The NASA robotic explorer has travelled 1.4 billion miles since its launch, and is now set to come closer to Jupiter, the largest planet in the solar system, than any previous spacecraft The probe will gather data related to Jupiter’s composition, and its gravitational and magnetic field.

Juno will come to within 2,900 miles of the planet in this mission, exposing it to extremely harsh environments, and specifically a radiation storm generated by Jupiter’s extremely powerful magnetic field.

©NASA

Close to the surface

It is necessary for the probe to get this close to the planet in order to gather the relevant data. “We are not looking for trouble, we are looking for data. Problem is, at Jupiter, looking for the data Juno is looking for, you have to go in the kind of neighbourhoods where find trouble pretty quick,” says Dr Scott Bolton, Juno’s Principal Investigator.

The spacecraft is designed to cope with these harsh environments and gather data. Juno’s flight computer is housed in a titanium armoured vault, while the spacecraft also carries several sophisticated instruments, including magnetometers, a microwave

radiometer and a spectrograph, designed to investigate Jupiter’s atmosphere, environment and overall composition.

The probe is due to spend a year orbitting Jupiter, gathering data on its water content, its magnetic fields, and also looking to find evidence of a solid core. While Jupiter is known to be comprised primarily of hydrogen, less is known about the core of the planet, which could hold some heavier elements.

A thundering storm on HAT-P-11b The next time you find yourself caught in a thunderstorm, be thankful that you’re not on HAT-P-11b, an exo-planet around 122 light years from earth. Researchers from the University of St Andrews have found that the planet experiences violent lightning storms, millions of times more powerful than we experience on earth.

Unexplained signals

This work has its roots in the findings of French researchers from 2009, who observed unexplained radio signals from the planet, which is located in the Cygnus constellation and orbits the star HAT-P-11. The researchers then looked to investigate the origin of the signal, using sophisticated techniques to observe the atmosphere on the exo-planet.

“We assumed that this signal was real and was coming from the planet. Then we asked the question: could such a signal be produced by lightning in the planet’s atmosphere? And if yes, how many lightning flashes would be needed for it?” explains Gabriella Hodosan, a PhD student participating in the study.

The researchers found that 53 lightning flashes over a square kilometre would explain the radio signal that the French team observed, lightning on a scale that is difficult to picture.

“Imagine the biggest lightning storm you’ve ever been caught in. Now imagine that this storm is happening everywhere over the surface of the planet. A storm like that would produce a radio signal approaching 1 percent of the strength of the signal that was observed in 2009 on exoplanet HAT-P-11b,” says Dr Paul Rimmer, a co-author of the paper.

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©NASA/JPL-Caltech

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Fuelling tomorrow

becoming more popular. This is still an expensive technology, and a technology that needs further development.”

The wider public remains unaware that hydrogen technologies are available on the commercial marketplace, according to Bart Bieybuck of the Fuel Cells and Hydrogen Joint Undertaking. A public-private partnership supporting research, development and demonstration of fuel cell and hydrogen technologies, the Fuel Cells and Hydrogen Joint Undertaking aims to help bring these technologies to the marketplace.

There is a general lack of awareness that these technologies are available now, something which clearly limits their wider commercial potential. “When I talk to people in the street, they still think of it as something which is about 10-20 years away, and this is wrong,” stresses Bieybuck. “It’s there today and they can buy it if they want it.”

Hydrogen buses

This process is already in train. There are nearly 100 hydrogen buses on European roads, and hydrogen-fuelled home heating systems are becoming more widely available. “We now see the first products coming onto the market ,” says Bieybuck. “Cars and buses have been ready for several years now and micro CHP units are

Superbug grown in lab for the first time Researchers have managed to grow norovirus in a laboratory, which will make studying it far easier Norovirus, the leading viral cause of acute diarrhoea in the world, has always been incredibly difficult to study because scientists had not found a way to grow it in a lab.

Now, more than 40 years after Dr Albert Kapikian identified human noroviruses as a cause of severe diarrhoea, scientists have finally grown samples - after adding bile to the culture.

This work, published in Science by researchers at Baylor College of Medicine, represents a major step forward in the study of human gastroenteritis viruses, because it will allow researchers to explore and develop procedures to prevent and treat infection and to better understand norovirus biology.

The benefits of hydrogen-powered vehicles in particular are clear.

Alongside their extended range, hydrogen vehicles are also highly environmentally friendly, an issue which Bieybuck says is an increasingly important consideration for consumers. “People like their way of living, they like their comfort, so they don’t want to change that. But, simultaneously, there is a growing consciousness of the need to address environmental issues,” he says.

Round the world in a solar aircraft The Swiss aircraft Solar Impulse 2 has completed the latest stage of its round-the-world journey, arriving in Seville after a three-day flight from New York. Designed to promote the use of renewable energy and clean technologies, the aircraft has a wingspan of 72 metres and weighs just 2.3 tonnes, a design radically different to most of the planes that we see in our skies.

It differs to most aircraft in several other crucial respects as well. Designed to use only the energy stored within its batteries, the Solar Impulse 2 makes use of ultralight materials to minimise weight; the wingspan is covered in 17,000 photovoltaic cells to capture solar energy, while energy dense batteries are used to store it efficiently, Since setting off from Abu Dhabi on 9 March 2015, Solar Impulse 2 has travelled over 20,000 kilometres, already becoming the first solar-powered plane to make an ocean crossing. The project is now planning the next stage of the route, with pilots Bertrand Piccard and Andre Borschberg set to continue sharing duties.

Noroviruses, also known as the cruise ship viruses, do not grow in laboratory cultures that traditionally support the growth of other viruses, such as transformed cells that are derived from cancerous tissues. Co-authors endowed Professor Dr Mary Estes, Cullen and assistant professor Dr Sue Crawford said: “This new cultivation system will finally allow us to gain an insight into how this virus causes disease.

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Life after death?

It’s something we all have to face at some stage, but the actual process of death and the time at which it occurs may differ from what had been commonly thought. Recent research calls into question some of our most fundamental ideas about the end of life, with scientists discovering that some genes in animals carry on working for up to 48 hours after death.

Grimsel car is quick out of the blocks The Grimsel electric racing car took less than a year to develop, now the vehicle has a place in the record books.

The Grimsel set a new record for acceleration by a batterypowered vehicle at an airbase near Zurich, taking just 1.513 seconds to go from 0kph to 100kph.

A group of 30 students at ETH Zurich and Lucerne University of Applied Sciences and Arts developed the vehicle, using advanced methods to develop a lightweight car. It weighs just 168 kg, with a sophisticated traction system regulating the performance of each individual wheel.

The vehicle has already enjoyed great success in the international Formula Student competition, and with that kind of speed out of the blocks, we’re sure that there’ll be more victories in future.

A team of scientists at the University of Washington, Seattle, led by Peter Noble and Alex Pozhitkov, investigated the activity and energy levels of genes in the organs of mice and zebrafish immediately after death. Researchers found that some genes remained active long after the animal had died, while hundreds of genes ‘woke up’ after death.

This research has important implications beyond our ideas of what death actually means, potentially influencing organ transplants and forensic science. Some of the genes thought to ‘wake up’ after death have been associated with liver cancer, which might be one of the factors behind the high risk of liver cancer in transplant recipients.

The moral of driverless cars The development of driverless cars demands not only technical expertise, but also deep debate on some searching moral questions. Should a car facing a possible accident place greater weight on the welfare of its passengers or the surrounding members of the public for example?

It is questions like this that are holding back the possible introduction of driverless cars, as much as any technical problems around their actual operation. The issue is the subject of a research paper published in the latest edition of Science.

“Autonomous cars can revolutionise transportation,” says co-author Iyad Rahwan, a cognitive scientist at the University of California, Irvine and MIT. “But they pose a social and moral dilemma that may delay adoption of this technology.”

Credit: ETH Zurich / Alessandro Della Bella

such situations, the car would again have to make a kind of moral judgment, potentially taking into account age, gender and a whole raft of other issues.

Further research

These are the kinds of dilemmas which may slow down the development of self-driving cars. With companies like Google continuing to explore the potential of autonomous vehicles, the study authors called for further research into algorithmic morality.

“Figuring out how to build ethical autonomous machines is one of the thorniest challenges in artificial intelligence today,” they write. “As we are about to endow millions of vehicles with autonomy, a serious consideration of algorithmic morality has never been more urgent.”

Moral dilemmas

The paper itself set out to gauge opinion on how autonomous cars should operate in morally complex situations. While researchers found that 76 percent of people agreed a driverless car should sacrifice its passenger rather than hit a larger group of pedestrians, a more complex picture emerges from other responses.

Researchers found that while people agreed autonomous vehicles should be programmed to minimise deaths caused by car accidents, people weren’t keen to actually buy a vehicle programmed to put a higher value on somebody else’s life.

Then there are more common scenarios, where a car might be about to cause less serious harm to bystanders or car occupants. In

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Google’s self driving car. Image credit: Google

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Technical developers, social innovators The silicon valley area, located to the south of San Francisco, has long been known as a hotbed of technological innovation, with both global giants and smaller start-ups looking to develop the next generation of high-tech products A whole eco-system of research, development and finance has grown around silicon valley, supporting technical development and turning new ideas into novel products, helping establish the area as an industrial powerhouse.

Universal basic income

This commitment to technological innovation is matched by a willingness to explore radical social ideas. The venture capital company Y Combinator, with the support of several prominent local businesspeople, has announced plans to conduct a basic income experiment in Oakland, California.

Around 100 families in the area will be given a basic income of between $1,000 and $2,000 a month to spend as they choose in the study. This is motivated in large part by a desire to explore new ideas around income distribution, as technology continues to affect the employment market.

“The motivation behind the project is to begin exploring alternatives to the existing social safety net,” said Elizabeth Rhodes, the Research Director for Y Combinator’s Universal Basic Income (UBI) project.

“If technology eliminates jobs, or jobs continue to become less secure, an increasing number of people will be unable to make ends meet with earnings from employment,” she continued.

Pilot study

A lot of data will be gathered from the pilot study, which could prove relevant to later UBI projects, as politicians and economists continue to grapple with changes to the labour market as technology plays an ever-greater role in our everyday lives.

The idea of a universal basic income is also gaining traction in Europe, with UBIE (Unconditional Basic Income Europe) established in 2013 to promote the idea, bringing together more than 25 countries from across the EU. The Dutch city of Utrecht plans to pay citizens a basic income, regardless of their work status, while the Green Party in the UK has also outlined ideas around a citizen’s income.

The robots are coming

The Canadian-American entrepreneur Elon Musk is widely known as the founder of SpaceX, a company which manufactures and launches advanced rockets and spacecraft, but he’s also involved in a number of other areas of business. Musk also sponsors OpenAI, a non-profit research company aiming to ensure the benefits of Artificial Intelligence (AI) are widely distributed.

Household robot

The company was established in large part to counter-balance the huge investments being made in AI by major multi-nationals, and to prevent them from gaining a dominant position. The company is working across four main technical goals, including work to enable a physical robot to perform basic housework and everyday chores.

So could we be dialing up a robot to clean up the kitchen within a few years? It’s a nice thought, but there are some significant technical challenges to negotiate first. OpenAI is not actually building the machine itself, but rather working to develop learning algorithms, so that the eventual robot is reliable and intelligent, capable of adapting to different tasks.

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Researchers at Open AI believe that it will eventually be possible to develop sufficiently reliable learning algorithms to create a general purpose robot capable of performing basic housework and domestic tasks. Drop your dishcloths, the robots are coming....

Meet the techno-politician

The general public could be forgiven for thinking there are only two contenders for the US Presidency in the forthcoming elections, but there will be another name on the ballot paper come November, and he’s got some radical ideas about technology. Zoltan Istvan, a science fiction writer and futurist, is the leader of the Transhumanist party and is running for President.

The man himself accepts he’s unlikely to be occupying the White House this time next year, but he hopes to at least promote his ideas and animate the debate. Transhumanism, a movement which looks to use emerging technologies to enhance and improve human capabilities, is central to Istvan’s philosophy.

Policy platform

This is reflected in the Transhumanist party’s platform. Istvan wants to put science, technology and health at the heart of the government’s agenda, with the Transhumanist party’s platform stating a commitment to; ‘spread a pro-science culture by emphasising reason and secular values.’

That hasn’t always gone done too well in the more religious parts of America, but he’s found a more receptive audience on the coasts.

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The party platform also advocates reducing the size and cost of government by streamlining new technologies, and also using new technologies to promote direct digital democracy.

There’s always an appetite in America for new thinking, and while Istvan’s ideas are outside the current mainstream, political analyst Roland Benedikter believes he can help shape the debate.

“Winning here means getting attention for an important topic that may become crucial over the coming decades,” he says.

“His intention is to raise awareness for the necessity of a much broader, deeper, and more differentiated debate on the future of the human being, and of being human, in an age where the human body is beginning to meld with technology,” he continues.

Futurist agenda

These questions are likely to grow more prominent over the coming years, and Istvan hopes that the American public will be more receptive to his ideas by 2024. “By that point, many robots will have taken our jobs, we’ll have AI around the corner, we’ll be choosing hair and eye colour and augmenting children’s intelligence,” he predicts.

“If this starts happening, politicians will have to start addressing transhumanism and the civil rights challenges associated with it.

We’re just not there yet,” he says.

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Thapsia’s in field; Photo by Henrik Toft Simonsen.

A new route to anti-cancer drugs Certain bioactive compounds found in plants have anti-cancer properties, now researchers aim to develop new, more sustainable methods of producing them. The DrugTissueCult project focuses on Thapsigargin and Withaferin A, aiming to find alternative ways to produce the chemicals used in anti-cancer drugs, as Associate Professor Henrik Toft Simonsen explains The bioactive compounds

found in plants have long been used in medicine, now researchers are seeking to harness their properties in the fight against cancer.

It has recently has been discovered that two compounds, Thapsigargin and Withaferin A, have anti-cancer properties, an area that forms the primary research focus for the DrugTissueCult project. “The idea was to find alternative ways to produce chemicals that are in clinical trials for new anti-cancer drugs. Instead of trying to grow the plants in the wild, we can use the plant tissue culture, to provide a more uniform production line,” says Henrik Toft Simonsen, the co-coordinator, an Associate Professor at the Technical University of Denmark. This builds on knowledge of the chemical structure of these compounds.

“The chemical structure of these compounds are known, we also know about the first steps in biosynthesis and how they are isolated,” continues Henrik Toft Simonsen. “What is not known, but is becoming clearer, is where in the plant these compounds are made? What tissues should we focus on?”

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Tissue culture Researchers aim to decipher the complete metabolic pathway in each relevant plant species and identify the key genes involved in the biosynthesis of Thapsigargin and Withaferin A. This will help in the development of a reliable, sustainable method of producing these compounds,

Thapsai fruits; Photo by Henrik Toft Simonsen. that doesn’t rely on the harvesting of wild plants. “The problem with the current knowledge of these plants is that we can’t really grow them, and it’s difficult to devise a production system that doesn’t rely on harvesting wild plants. That’s not

really a sensible strategy, as you will just wipe out the natural habitats of these plants. So the idea is that we will try to establish another production system,” says Henrik Toft Simonsen. The current methods of producing both Thapsigargin and Withaferin A rely largely on natural plants; while there are alternatives for Withaferin A, they are not cost-effective.

“It is possible to make Withaferin A synthetically, but it’s very expensive,” explains Henrik Toft Simonsen.

The project’s research into plant biosynthesis will underpin the development of a new production system. While many groups are working on the metabolic pathway of Withaferin A, Henrik Toft Simonsen says his group is currently one of few investigating Thapsigargin. “We are 2-3 steps down the road for both pathways, and there are probably 6 or 7 more steps to be identified,” he outlines. This work could lead to more efficient production of the compounds. “With the techniques we are using we can measure differences in expression in genes, then get an idea of what genes are involved when production

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At a glance Full Project Title Plant Tissue Cultures as New Production Platforms for Terpenoid Based Anti-Cancer Drugs (DrugTissueCult)

Figure 1: project overview - how we will make thapsigargin and withaferin A - by: Henrik Toft Simonsen. levels are higher,” continues Henrik Toft Simonsen. “Then you’re limiting the number of genes you have to look into and design your bio-chemistry for, bringing it down to a workable number, rather than having to consider many thousands of genes. The project’s industrial partner Alkion Biopharma is very interested in this, because it will help them design future plant cell lines, where selected genes can be upregulated, further enhancing production of certain compounds.”

This is an important issue in terms of the applicability of the compounds in new pharmaceutical drugs designed to combat cancer, an issue high on the global health agenda. With both Thapsigargin and Withaferin A in the latter stages of clinical trials, Henrik Toft Simonsen says that the most significant hurdle to negotiate before they can be used in a clinical setting is likely to be producing the actual compounds in sufficient quantities. “The

which is of course a key issue in the pharmaceutical industry. While cancer is a global health priority, Henrik Toft Simonsen is aware that new drug development methods have to be costeffective. “When you submit an application you have to show that you have a viable method, that the drug isn’t going to cost billions of Euros. You cannot make it unless it is economically viable,” he says.

The project’s research has been built on close collaboration between industry and academia, and Henrik Toft Simonsen is optimistic that their work will have a wider impact beyond the research sphere.

“I think the latest steps we are taking will secure a reasonable production of both of these molecules, and also pave the way for similar set-ups with further molecules.

Alkion Biopharma has learnt a lot about the technology over the last year or so, while research continues into both molecules,” he continues.

The problem with the current knowledge of these plants is that we can’t really grow them, and it’s difficult to devise a production system that doesn’t rely on culling wild plants. That’s not really a sensible strategy, as you will just wipe out the natural habitats of these plants. So the idea is that we will try to establish another production system major problem is not so much getting the drugs approved, it’s more about producing enough of the actual compounds. That’s what we are trying to solve here,” he explains. Plant-based bioreactors are being used by the project to produce Thapsigargin and Withaferin A in large quantities; Henrik Toft Simonsen says this technology is well established. “It is capable of producing large quantities, and it’s already being utilised for some other compounds in fact,” he outlines.

This is central to the economic viability of specific biotechnological applications,

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Cancer treatment This includes both research into their potential impact on other diseases and efforts to target them more precisely when used in cancer treatment. This could help limit the side-effects of treatment.

“Researchers are developing methods to target the molecules more precisely,” outlines Henrik Toft Simonsen. The work on Thapsigargin is going quite well so far, while Withaferin A is proving to be slightly more difficult to work with. “The mechanism of action is slightly different. It’s a bit more complicated,” says Toft Simonsen.

Project Objectives In DrugTissueCult we will develop a large collection of tissue cultures line producing Thapsigargin and Witheferin A. These lines will be used to develop elite lines that produce high amounts of the target molecules and this is the major milestone of DrugTissieCult.

Project Funding 2 Marie-Curie stipends for two phd students. Aproxximately 600.000 euro.

Project Partners Department of Plant and Environmental Sciences, University of Copenhagen. Alkion Biopharma, France. Department of Department of Biotechnology and Biomedicine, Technical University of Denmark.

Contact Details Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Building 223 2800 Kgs. Lyngby, Denmark T: +45 2698 6684 E: hets@dtu.dk W: www.drugtissuecult.eu W: http://www.bio.dtu.dk/english/Research/ Research-groups/Photosynthetic_Cell_Factories

Henrik Toft Simonsen, PhD, MSc

Henrik Toft Simonsen is an Associate Professor in the Department of Biotechnology and Biomedicine at the Technical University of Denmark, a position he has held since January 2016. Previously, he worked as an Associate Professor at the University of Copenhagen, after gaining his PhD in 2002 from the School of Pharmacy at the same university.

Co-Coordinator of: www.drugtissuecult.eu Participant in: www.medplant.eu, www.spotlight.ku.dk Founder of: www.mosspirationbiotech.dk

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Mono-oxo-bis-dithioveratrol-molybdate – in solution a model for arsenite oxidase and a coordination polymer in the solid state. The polyhedrons illustrate the coordination geometry around the molybdenum centers. Purple = molybdenum, green = sodium, yellow = sulfur, red = oxygen, grey = carbon, white = hydrogen.

Researchers aim to get to the heart of enzyme activity Molybdenum cofactor-dependent enzymes play a central role in many important biological processes, and severe health problems result when they fail to develop properly. Professor Carola Schulzke tells us about the work of the MOCOMODELS project in synthesising complexes that mimic the natural molybdenum cofactor of the respective enzymes A failure in

the process of generating the three main molybdenum-dependent enzymes, sulfite oxidase, xanthine oxidoreductase and aldehyde oxidase, is the root cause of both molybdenum cofactor deficiency (MocoD) and sulfite oxidase deficiency (iSOD), two rare diseases which cause neurological damage. Based at the University of Greifswald in Germany, Professor Carola Schulzke is the coordinator of Mocomodels, an ERC-backed initiative investigating these enzymes, which are

The project aims to synthesise a large variety of molybdenum complexes that mimic the natural molybdenum cofactor of the respective enzymes, the most important of which is sulfite oxidase. The natural co-factor itself is quite complex. “It has a unique ligand system, which is biologically made from guanosine triphosphate (GTP), so from a nucleoside triphosphate. It has properties which are absolutely unique for this type of enzyme,” explains Professor Schulzke.

Researchers are building on knowledge

We want to understand how these molybdenumdependent enzymes work. In the long run this could help us synthetically generate drugs that could counter the effects of these diseases common to all kingdoms of life. “We want to understand how these enzymes work.

In the long run this could help us synthetically generate drugs that could counter the effects of these diseases,” she outlines. This is very much a long term goal however, and the project’s immediate focus is more on fundamental research into how these enzymes’ active sites operate. “The project aims to understand what components are needed in order to make comparatively small active model compounds which can interact with specific proteins in order to restore activity,” says Professor Schulzke.

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of the structure of the molybdenum cofactor to develop these complexes, and are also considering their suitability to bind in the active site of the protein. “We basically broke the structure down, and are trying to model certain aspects of the complex. We will leave some parts out, in order to see if they are really crucial for activity or stability, or if we can just ignore them, which will make our work much easier,” continues Professor Schulzke. “We aim to find the compound that has the required level of activity, while at the same time being as simple as possible.”

Molybdenum complexes A number of different approaches are being used to synthesise the molybdenum complexes, building on fundamental knowledge of the co-factor and its structure. The project is comprised of four main sub-projects, with researchers looking at the common features of these enzymes, one of which is the presence of a metal. “The metal in the middle is most often molybdenum, but we also sometimes see tungsten and we will test rhenium as a substitute,” says Professor Schulzke. The project is looking at alternative metals, investigating the potential benefits they offer in terms of stability and activity.

“The human organism only uses molybdenum in this kind of enzyme, but tungsten is used in nature, in particular in organisms which have been on the earth for a very long time,” outlines Professor Schulzke. “Tungsten is known to work in exactly the same way as molybdenum, with the same coordination in the enzymes. There is slightly different reactivity of course, and there are also organisms which can use both, depending on the conditions.”

There has been a gradual evolution over time from tungsten towards molybdenum, with more modern organisms typically using molybdenum in these enzymes.

Nevertheless, tungsten is known to behave very similarly to molybdenum, while Professor Schulzke says it also offers other benefits.

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“It’s easier to oxidise than molybdenum, which can have an impact on stability. We hope that replacing molybdenum with tungsten will represent another means of increasing stability,” she explains. The third metal is rhenium, which is to the right of tungsten in the periodic table, so it has a diagonal relationship with molybdenum. “Rhenium has been shown to catalyse oxygen-atom transfer, so we can use it for oxygen-atom transfer with dithiolene ligands,” continues Professor Schulzke. “We are very curious about the impact on proteins of going from molybdenum to rhenium. It might be that we can reach the perfect balance between activity and stability.”

Researchers have made tungsten and rhenium complexes and tested them for catalytic activity, with results so far showing that tungsten is very often a slower catalyst than molybdenum, while rhenium is fairly similar. The project is also investigating whether these complexes could be incorporated within biotechnologically generated apoenzymes, and are assessing their suitability and effectiveness as a treatment for iSOD. “Our partner in Postdam is producing the enzymes with the proteins. We incubate our complexes together with the enzymes, and then we basically take the proteins and enzymes

out of this incubation solution, and test them to see whether the metals are present in the protein or not,” explains Professor Schulzke. While the initial results were disappointing, Professor Schulzke says researchers are learning

Schulzke. There is a clear relationship between the stability of the active site and the ability to catalyse oxygen atom transfer, which is an important consideration in terms of the potential clinical applications of these complexes.

“The protein has an important role to play in terms of stabilising the active site.

Recent tests have shown that we can combine our active sites with the protein,” continues Professor Schulzke. “If we want to look towards using these complexes in a hospital setting then I think we need to prioritise stability.”

Treatment Claudia working with the stills. about the underlying factors which result in better binding and better activity. “What seems to be really important is that our models have the potential to induce hydrogen bonding,” she outlines.

A variety of sophisticated analytical methods have been used in the testing process. Most of the complexes have been found to be catalytically active, but the more active they are, the more sensitive they are. “The more sensitive they are the less suitable they are for testing in a biological environment,” says Professor

This work holds real importance to the treatment of both iSOD and MocoD. Both are extremely rare diseases, with only around 100 cases reported last year, yet Professor Schulzke believes it is likely that this figure understates the true picture.

“It’s not so easy to diagnose, as there are different types of deficiency related to the molybdenum enzymes. To diagnose MocoD, you need to first have the idea that this might be behind the symptoms,” she says. Early diagnosis is crucial to patients’ prospects, and recent years have also seen advances in treatment, with a patient in Australia becoming the first to be successfully treated for MocoD in 2009; new treatment methods are being

Yulia working in the Dry-/Glove-box.

Mohsen at his fume hood.

Ivan working with the IR spectrophotometer.

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At a glance Full Project Title Synthesis of mono-dithiolene molybdenum complexes and their evaluation as potential drugs for the treatment of human isolated sulfite oxidase deficiency (MOCOMODELS) Project Objectives Two symptomatically indistinguishable fatal diseases (molybdenum cofactor deficiency (MocoD with subtypes A and B) and isolated sulfiteoxidase-deficiency (iSOD)) are caused by a failure at different levels of the expression and assembly of a certain group of enzymes. While some MocoD patients have been successfully treated by injection of an organic molecule that takes part in the proteins’ development there is no cure for iSOD. This project aims to develop a substitute for the very sensitive metal based part of the enzyme, to test its potential to generate an active enzyme together with the biotechnologically produced enzyme- peptide and to evaluate the semisynthetic enzyme’s applicability as a treatment. By developing distinct synthetic model compounds with various functional groups present we hope to find the best compromise between synthetic feasibility, stability and reactivity. Our findings will also provide a deep insight into the structurefunction relationships of the molybdenum dependent enzymes.

Project Partners Professor Silke Leimkühler, Institut für Biochemie und Biologie, Universität Potsdam Contact Details Professor Carola Schulzke, Institut für Biochemie Ernst-Moritz-Arndt Universität Greifswald Felix-Hausdorff-Straße 4 D-17487 Greifswald T: +49 (0)3834 86 4321 E: carola.schulzke@uni-greifswald.de W: http://cordis.europa.eu/project/ rcn/101595_en.html

Nicolas working on the X-ray diffractometer.

developed. “A group in Cologne is using biotechnology methods to producing a precursor of the ligand. Children who are diagnosed soon after birth, or possibly even pre-natally, and then treated immediately, can develop quite normally,” continues Professor Schulzke.

The project’s long-term goal is to develop a compound which contains all the indispensable functional groups while remaining stable and active, which will provide a new treatment option. More immediately, Professor Schulzke says her research will help build a deeper understanding of structure-function relationships in the active site. “We hope

that we can determine which of the functions are really necessary in order to maintain activity,” she outlines. From this, researchers can then analyse the complexes and work to improve their stability, to a point where they could be used in treatment; this is very much a long-term goal however, and Professor Schulzke plans to pursue further research into the co-factors. “I will keep working on refining and designing co-factor models, and hopefully they can be used as treatment for this disease in the future.

Within the timeframe of this ERC project we will understand exactly what we have to do in order to get there,” she says.

The current ERC team (left to right: Mohsen, Nicolas, Claudia, Carola, Yulia, Ivan).

Professor Carola Schulzke Carola Schulzke studied chemistry at the Universität Hamburg, Germany and obtained her PhD 2000 with Dieter Rehder in the field of bioinorganic vanadium chemistry.

After postdocing with Sandro Gambarotta in Ottawa she started to work on her own project with Felix Tuczek in Kiel, Germany. 2002-2009 she worked as juniorprofessor at the GeorgAugust-Universität Göttingen and 2009-2012 as assistant professor at Trinity College Dublin. 2012 she became a professor (chair for bioinorganic chemistry) at the Ernst-MoritzArndt-Universität Greifswald taking the ERC project MocoModels with her. Her main research interests are synthetic bioinorganic chemistry and crystallography.

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An environmentally-friendly anthrax decontaminant Anthrax remains a significant threat to health in certain parts of the world, and some areas remain contaminated with spores. The AEDNET project is developing an environmentally-friendly approach to decontamination based on spore biology, work which also holds implications for civil security, as Professor Les Baillie explains A disease of

animals caused by the spore-forming bacterium Bacillus anthracis, anthrax remains a significant threat to the health of both animals and humans in certain parts of the world. Some countries, particularly around the Caucasus, lack the resources to decontaminate animals who have died of the disease, which can cause long-lasting problems, as Professor Les Baillie of the AEDNET project explains. “One approach is to just bury the animal, with the spores inside, in a hole in the ground,” he says.

The spores are highly resilient however, and can survive in soil for many years,

form, depending on the availability of food, as it has sensors that respond to food. If the food triggers are present, it will convert from the spore form to the vegetative form.

And when the food runs out, it converts back into the spore again,” explains Professor Baillie. Researchers have identified these food triggers, which are cheap and easily available, and are now looking to apply them. “By applying these food triggers to soil containing the spores, we can induce the spores to think that there’s lots of food there, and to convert back to the vegetative form,” continues Professor Baillie.

The B.anthracis bacteria is still present at

The bacterium can interchange between the spore form and the vegetative form, depending on the availability of food, as it has sensors that respond to food. If the food triggers are present, it will convert from the spore form to the vegetative form leaving burial sites contaminated. “Over time the animal will rot away, but the spores will remain. If there is a flood, the water table moves up, and the spores come to the surface again. So with a burial site, what you basically have is a repository for B.anthracis spores,” outlines Professor Baillie. “These spores won’t go away until you’ve actually decontaminated the site.”

Decontamination The standard approach historically has been to use extremely toxic carcinogens like formaldehyde or bleach, but now researchers in the AEDNET project are developing a more environmentallyfriendly approach based on B.anthracis biology. “The bacterium can interchange between the spore form and the vegetative

this point, but it’s now in a more vulnerable form, and researchers can look to eradicate it.

The project is developing an approach based on the use of bacteriophages, a type of virus that infects only bacteria. “The virus is very specific for a particular type of bacteria. So a bacteriophage acting against B.anthracis will only kill the B.anthracis bacteria,” outlines Professor Baillie. These viruses are present naturally in the soil, often in the same location as the pathogen; Professor Baillie and his colleagues have isolated viruses at several animal burial sites. “We wanted to find burial sites that had bacteria in that we could then kill,” he says. “We needed to define the sites, we needed to isolate the viruses, and we needed to grow them in the laboratory. We also needed to characterise the anthrax at those sites. Finally, we needed to come back Researchers in Turkey sampling a B.anthracis spore contaminated animal burial site.

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in and treat the site, to see if our phage-food combination was effective at reducing the number of bacteria at the site.”

This research has also attracted the attention of defence authorities planning for the worst-case scenario of anthrax being used as a biological weapon. There is a precedent for this scenario; the US experienced a spate of anthrax attacks in the aftermath of 9/11, when letters containing spores were sent through the post to several individuals and media organisations. “The authorities had to decontaminate a number of buildings. On one they used chlorine dioxide gas, which is explosive in sunlight, and they also used formaldehyde. The estimated clean-up cost for the letters in the US was approximately 1 billion dollars. That was the cost of responding to a small-scale, low-tech attack, so imagine the cost associated with a large scale terrorist attack against a major city in Europe,” outlines Professor Baillie. The project’s research holds clear relevance in these terms. “The authorities are interested in approaches that have no collateral damage, and are very usable, cheap and scalable,” says Professor Baillie.

Anthrax Environmental Decontamination Network (AEDNET) Professor Les Baillie Professor in Microbiology School of Pharmacy and Pharmaceutical Sciences College of Biomedical and Life Sciences Cardiff University Redwood Building King Edward VII Avenue Cardiff CF10 3NB Wales T: +44 (0)29 208 75535 E: baillieL@cf.ac.uk W: https://aednetproject. wordpress.com/

Professor Les Baillie has considerable experience of these issues gained through working for the UK Ministry of Defence as the lead for anthrax related research. He currently serves as an expert advisor to a number of UK ministries who are active in this area.

Once the data has been reviewed by the relevant authorities it will be made available to interested parties by participating in major congresses, seminars and trade fairs. Information will also be disseminated via the project website and in the scientific press.

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A very broad and heterogenous group of disorders, cerebellar and brainstem congenital defects (CBCDs) can have a severe impact, yet the genetic basis of many of these disorders is still not fully understood. Professor Enza Maria Valente tells us about her work in investigating the basis of these defects, and its wider impact on the prognosis and management of CBCDs

Sagittal (upper panels) and axial or coronal (lower panels) brain MRIs of distinct CBCDs. First column: Joubert syndrome; second column: Dandy Walker syndrome (upper), cerebellar dysplasia with cysts (lower); third column: primary brainstem malformation; fourth column: ponto-cerebellar hypoplasia.

Understanding the basis of cerebellar defects The underlying basis

of many CBCDs, including Joubert syndrome, ponto-cerebellar hypoplasias and Dandy-Walker syndrome, is still not fully understood. Based at the University of Salerno, Professor Enza Maria Valente is the coordinator of the CBCD project, an ERC-backed initiative pursuing research in this area. “This a very broad and heterogenous group of disorders. Mainly these malformations are not progressive disorders, but relate to defects in the cerebellum and/or in the brainstem arising during embryonic development,” she explains. Some of these disorders can be diagnosed prenatally, through ultrasound scans and/or foetal MRIs, yet much remains to be learned about their genetic basis, as well as their clinical progression and the prognosis for patients. This is of course a major concern for the families affected. “If a disorder is diagnosed prenatally, families may decide to interrupt the pregnancy because they’re uncertain about the prospects of their child improving,” says Professor Valente Many CBCDs share certain core features, such as hypotonia, ataxia, abnormal ocular

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movements and psychomotor delay. It can be difficult to identify the precise nature of the malformation, especially at onset. “This is what makes it complicated to diagnose and classify these patients, because the same clinical presentation may underlie different diseases, and brain imaging is essential to

Multi-disciplinary approach Researchers aim to both investigate the genetic basis of CBCDs, and also improve the way these disorders are managed. The project is following a multidisciplinary approach to this work, combining several study methods across a large cohort of

neurological presentation of CBCDs usually vary in severity, but the core features can be very similar, especially at onset The

reach a correct diagnosis,” outlines Professor Valente. Improving the classification of CBCDs is thus an important part of the project’s research agenda. “Despite the impressive progress made in the past decade, the availability of genetic testing is still relatively limited at the moment, with consequent difficulties in providing an accurate prognosis and genetic counselling to the families,” says Professor Valente. “Also, the management and diagnostic procedures are not always very well-defined, and we have limited knowledge about the pathogenesis of some CBCDs.”

patients with various CBCDs; one workpackage is focused on clinical and neuroimaging. “The main aim of this workpackage is to recruit a large cohort of patients. We then perform a detailed clinical and neuroimaging characterisation of these patients,” says Professor Valente. These patients are divided into sub-groups based on the specific type of malformation, from which Professor Valente and her colleagues will look to build a deeper understanding of CBCDs. “We aim at developing specific correlates between the type of malformation

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At a glance

and the phenotypic spectrum, through early assessment and a follow-up of these patients,” she outlines. “We also use more sophisticated neuroimaging approaches to study malformations in a sub-set of patients, to better understand the problem in terms of brain development.”

The next two workpackages in the project are focused more on unravelling the genetic basis of mendelian and sporadic CBCDs. It is known that most mendelian CBCDs are inherited in a recessive fashion, meaning that two mutations in a specific gene are required to develop the phenotype. “The commonest of these mendelian CBCDs is Joubert syndrome, but there are also others such as ponto-cerebellar hypoplasia or various forms of cerebellar hypoplasia/dysplasia, for which the genetic basis is only partially understood,” says Professor Valente. The project is studying over 500 patients with Joubert syndrome, which is typically diagnosed on the basis of a malformation called the “molar tooth sign”; Professor Valente and her colleagues are focused on genetic screening of these patients and identification of novel genes.

“We will analyse all the known genes and try to identify the genetic code,” she says.

“There is a high level of genetic heterogeneity – for instance, we know of over 30 genes that encode Joubert syndrome.”

A great deal has been achieved in this area, with the recent identification of several novel genes causative of distinct CBCDs. The project is also pursuing molecular studies into sporadic CBCDs, where it is more difficult to identify the precise cause of the malformation. “Many of these malformations only occur sporadically, so it’s very difficult to assess whether there is a major genetic component or not,” explains Professor Valente.

Different genetic causes may be responsible for these cases; Professor Valente aims to detect variations in the number of copies of specific genomic regions. “Also, we are selecting homogeneous groups of patients, and we will perform whole exome sequencing studies in the attempt to identify de novo mutations in the affected child that are not present in the parents,” she explains.

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Fundamental research A fourth workpackage centres more on fundamental research, developing a novel in vitro neuroembryonic model to study these malformations. This will enable researchers to explore the role and function of specific genes in the development of the cerebellum and brainstem. “By taking induced pluripotent stem cells from patients carrying genetic mutations and differentiating them towards cerebellar neuronal precursors, we can look to see whether and how the genetic mutations that we examined in previous workpackages affect neuronal development,” says Professor Valente.

The project also has access to follow-up information on some patients, from which researchers can draw insights into the pr最漀 nostic outcome of some CBCDs, and how these can be managed more effectively.

“We’ve done a cognitive study on about 50 Joubert patients and found that expressive language was more severely affected than comprehension for instance. This provides useful information to families on which areas to work on in rehabilitation,” outlines Professor Valente. “Also, we are following up on a large cohort of adult Joubert patients, and looking at questions around their quality of life.”

The idea is to correlate this follow-up information with findings on the severity of the phenotype when patients were younger.

This could help inform the prognosis and long-term management of CBCDs. “We need to address several fields, because people with CBCDs may have motor disabilities, intellectual disabilities, and also impaired vision. So this really affects their quality of life,” says Professor Valente. These CBCDs are generally not progressive though, and in some cases patients have shown improvement after rehabilitation, so if they are managed effectively then patients can still maintain a good quality of life. “It really depends on the degree of severity of the phenotype – for instance, some patients have a very severe intellectual impairment, while others can finish school with support, and even get a job in a protected environment,” explains Professor Valente. “The same applies for motor deficits – some cases are very severe, whereas others are very mild, and they can carry on with a nearly normal life.”

Full Project Title Understanding the basis of cerebellar and brainstem congenital defects: from clinical and molecular characterisation to the development of a novel neuroembryonic in vitro model (CBCD) Project Objectives Cerebellar and brainstem congenital defects (CBCDs) represent a heterogeneous group of disorders with high mortality and morbidity, recognised with increasing frequency due to advances in neuroimaging. Current challenges are: i) scarce applicability of existing classifications in clinical practice; ii) poor knowledge of genetic causes and pathogenesis; iii) limited access to genetic testing; iv) lack of prognostic indexes useful for management. This project addresses these challenges through a multidisciplinary approach combining clinical, neuroimaging, molecular and functional studies.

Project Funding The project is mainly funded by the European Research Council (Starting Grant nr. 260888).

Selected subprojects funded by Telethon Foundation Italy (Grant GGP13146) and by the Pierfranco and Luisa Mariani Foundation (PADAPORT).

Project Partners The project relies on a wide network of collaborators both in Italy and abroad.

Contact Details Professor Enza Maria Valente Section of Neurosciences Dept. of Medicine and Surgery University of Salerno T: +39 089 965095 E: enzamaria.valente@outlook.com

Professor Enza Maria Valente

Professor Enza Maria Valente is Associate Professor of Medical Genetics at the University of Salerno. She has an MD and Certification in Neurology from the Catholic University, Rome, and a PhD in Neurogenetics from UCL in London. Her research involves clinical, molecular and functional studies on pediatric ataxias and movement disorders.

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Human evolution goes under the genomic microscope

Figure 1. The phylogenetic tree of 456 whole Y chromosome sequences and a map of sampling locations. The phylogenetic tree is reconstructed using BEAST. Clades coalescing within 10% of the overall depth of the tree have been collapsed. Only main haplogroup labels are shown (details are provided in Supplemental Information 6).

Colors indicate geographic origin of samples (Supplemental Table S1), and fill proportions of the collapsed clades represent the proportion of samples from a given region.

Asterisk (*) marks the inclusion of samples from Caucasus area. Personal Genomes Project (http://www.personalgenomes.org) samples of unknown and mixed geographic/ ethnic origin are shown in black. The proposed structure of Y chromosome haplogroup naming (Supplemental Table S5) is given in Roman numbers on the y-axis.

Humans have dispersed widely across the globe over the last 100,000 years, during which time we have adapted to a diverse range of natural environments. The Maladapted project brings together phenotypic, genetic and demographic evidence to study genomic changes over this period, as Dr Toomas Kivisild and Dr Luca Pagani explain The ancestors of

modern humans are widely thought to have lived for millions of years in Africa before spreading to the other continents from 50-70,000 years ago, as part of the so called ‘Out of Africa’ expansion. The human genome has evolved significantly since this dispersal, as humans have adapted to the climate and environment in different parts of the world. Now, researchers in the Maladapted project aim to shed new light on this topic.

“The project is studying the parts of the genome that have undergone the most dramatic changes since the Out of Africa migration, and have potentially been affected by natural selection,” outlines Dr Toomas Kivisild, the project’s Principal Investigator. Researchers are looking at several different populations, aiming to identify which parts of the genome have

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experienced the highest degree of change.

“We are targeting the Siberian, South-East Asian and high altitude populations from South America, to identify the regions in the genome that are responsible for adaptation to extreme environmental conditions,” says Dr Kivisild.

These three regions were settled at different times. While the population in South-East Asia was established relatively soon after the Out of Africa migration, humans took longer to reach Siberia and the Americas. “The first evidence for anatomical modern humans in Northern Siberia would be around 35,000 years ago, while since then, the region may have been resettled on multiple occasions” says Dr Kivisild.

Humans who migrated to these regions faced significant challenges in terms of their ability to adapt to the environment in

which they lived. “That is something that we are investigating with genotyping and sequencing studies – what are the main genetic regions that have shown change over what is a relatively recent evolutionary timescale?” continues Dr Kivisild. “We are trying to link the genetic results we’ve gathered with different lines of evidence from other disciplines, including phenotypic data, while archaeological data will also inform us about the demographics.”

Human adaptation Researchers will focus on three major aspects of human adaptation in this work, namely climate, nutrition and lifestyle.

With their work on the Siberian population, researchers are looking for genetic signals related to adaptation to cold, while Dr Kivisild says diet is another important

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consideration. “Typically carbohydraterelated genes show adaptation in European populations. We have found that fat metabolism genes are highlighted in NorthEast Siberians. In particular, we have found a signal of strong positive selection associated with one mutation in a fat metabolism gene called CPT1A,” he says.

The same polymorphism had previously been associated with high infant mortality in the Canadian Inuits, raising a seeming paradox. “How can a variant that is associated with disease be related to positive selection?” asks Dr Kivisild. “We are following this study up with colleagues from the Wellcome Trust Sanger Institute, to find out whether there is something beyond the fat metabolism that this gene enables, and what the advantage could be.”

This is one of the project’s key findings so far on the North-East Siberian populations, while researchers have also been able to widen the geographic scope of their investigations. While the Maladapted

changed unusually quickly over a period of less than 10,000 years,” says Dr Kivisild.

The fitness of a species in evolutionary terms is always measured in terms of reproductive success.

However, there are also other factors to consider in terms of how well adapted humans are to modern environments, and our very evolutionary success may be the root of future problems. “If you have a species that is perfectly adapted – so a large number of offspring, that is resistant to predators and pathogens – then that would eventually lead to overcrowding,” points out Dr Luca Pagani, a specialist in Biological Anthropology currently working at the University of Cambridge.

It’s therefore difficult to say how well adapted modern humans are, and the extent to which today we are adapting the environment to our own needs. “It’s fair to say that we are creating our own environment, and buffering ourselves against environmental conditions with

We are targeting three different populations, the Siberian, SouthEast Asian and high altitude populations of South America, to identify the regions in the genome that are responsible for adaptation to extreme environmental conditions project focuses primarily on Siberia, South-East Asia and Americas, researchers also have access to data from over 120 population samples from across the world, from which new insights can be drawn into the Out of Africa migration.

Demographic history The wider goal in this research is to investigate how well adapted humans are to the environments in which we live today.

This is not an easy question to answer, and Dr Kivisild says it’s important to consider both demographic history and selection.

“We are trying to assess the extent of genetic differentiation, over time, in different populations living in different environments. In terms of demography, if we go through a population bottleneck, then this affects all our genes at the same time.

Whereas selection affects individual genes,” he explains. Researchers have investigated how humans adapted to the cold climate in north-east Siberia for example, looking at how specific genes changed over time. “The selection co-efficient was unusually high, higher than previous estimates on lactase persistence for example, a genetic variant which had already been shown to have

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our technology. There has been some debate in literature recently about whether this has decreased the role of natural selection,” says Dr Kivisild.

There remains a great deal of interest in ancient DNA, and while the Maladapted project will conclude in June, Dr Kivisild and his colleagues plan to pursue further research into questions around how humans adapted to their environment. There has been a lot of discussion recently about a skin pigmentation gene found in the European population. “The estimated allelic age of this mutation is around 20,000 years or more. It is often thought that this mutation is the high-latitude adaptation to low UV conditions – and then the level of vitamin D would be the reason why this has reached high frequency in Europe,” outlines Dr Kivisild. Other studies have shown however that this mutation was almost completely absent during the mesolithic/ neolithic period, and was imported to Europe much more recently. “Therefore the selection, or the high frequency of this mutation, was probably derived from outside Europe. This raises interesting questions into what the adaptation was driven by,” continues Dr Kivisild.

At a glance Full Project Title An inter-disciplinary approach for identifying evolutionary active regions in the human genome (Maladapted) Project Objectives Over the past 100,000 years humans have dispersed globally and been repeatedly challenged to cope with the diverse range of natural environments and climate of our planet. The economic and cultural shifts from a non-sedentary lifestyle to a food producing and settled way of life in the last 10,000 years have further exposed us to a range of new diets and diseases related to increased population densities. In view of such major changes in the human environment, shifts brought about both by new lands, new socio-economic systems and changing climate, this project asks the question - How adapted to their environment are humans today?

Project Partners The work in this project has involved and led to many collaborators in this project, the main ones are Estonian Biocentre, University of Tartu, Wellcome Trust Sanger Institute, Institute of Biological Problems of the North, University of Berkeley, University of Copenhagen, National Cancer Centre Singapore, and others.

Contact Details Dr Toomas Kivisild, University Reader in Human Evolutionary Genetics Department of Archaeology and Anthropology, University of Cambridge Henry Wellcome Building, Fitzwilliam Street, Cambridge CB2 1QH T: +44 (0)1223 764703 E: tk331@cam.ac.uk W: http://cordis.europa.eu/project/ rcn/99495_en.html

Dr Toomas Kivisild

Toomas Kivisild is a Reader in Human Evolutionary Genetics at University of Cambridge with research interests in questions relating patterns of genetic diversity in living human populations to those from the past. His current work covers different aspects of human evolution, evidence of population structure and admixture, as well as addressing questions on human adaptabilty to different environments and the effect of culture on human genetic diversity.

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Supporting research into respiratory diseases Respiratory diseases remain among the biggest causes of death in Europe, underlining the importance of continued research. The European Respiratory Society funds a wide range of fellowships, including the RESPIRE2 programme, aiming to encourage talented researchers to tackle key challenges in the field, as Professor Maria Belvisi explains

ERS Career Development Fellowship event - taken at Munich Congress 2014 - Copyright@ERS.

The European Respiratory Society (ERS – www.ersnet.org) is one of the leading medical organisations internationally, promoting research into a wide range of respiratory diseases, including asthma, lung cancer and chronic obstructive pulmonary disease (COPD). While significant advances have been made in treatment over the years, around 600,000 people in the European Union’s (EU) 28 Member States still die every year from respiratory disease, underlining the importance of initiatives like RESPIRE2.

“The RESPIRE2 programme funds early-stage, two-year research fellowships thanks to cofunding from the EU through its Seventh Research Framework Programme (FP7).

The aim is to fund excellence in respiratory research and science, helping us to identify the leaders of tomorrow,” says Professor Maria Belvisi, ERS Research Director. Key gaps in research have been identified in the European Lung White Book (www.erswhitebook. org), which is published by the ERS. “The ERS is trying to address these gaps through supporting research fellowships, and the RESPIRE2 programme is the flagship,” continues Professor Belvisi.

“We fund a relatively small number of

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RESPIRE2 Marie Skłodowska-Curie fellows at host institutions of excellence.

The quality is very high in terms of the researchers’ qualifications and the projects that they are carrying out.”

This initiative builds on the success of RESPIRE1, a programme through which one-year research fellowships were funded between 2009-2013. Following the conclusion of RESPIRE1, the ERS worked to establish a new programme, thanks to EU co-funding, introducing many improvements. “We made it mandatory for host institutions to offer contracts to fellows, so they were fully covered during their fellowship, while we also extended the duration from one year to two years,” says Professor Belvisi. The ERS remains in close contact with many of the researchers involved in RESPIRE1, which Professor Belvisi says has been central to the development of the RESPIRE programme. “One of the aims of both RESPIRE1 and RESPIRE2 has been to ensure that researchers remain engaged in the ERS after they’ve completed their fellowships. For instance, most fellows are now involved in the ERS College of Experts, the body that participates in the peer review of fellowship applications,” she says.

Research excellence The fellow’s projects tend to be in basic and translational research across a wide range of respiratory conditions, from pulmonary hypertension, interstitial lung disease, cystic fibrosis and airway diseases, through to infections such as tuberculosis and pneumonia. While the 22 selected researchers enjoy a high degree of academic freedom in this work, Professor Belvisi says it’s also important to take the wider picture in terms of European health priorities into account. “We ask fellows and host centres to keep the ERS Roadmap (www. ersroadmap.org) in mind. That is a reference document that identifies the key priorities in the respiratory domain,” she outlines.

This research tends to be quite specialised in nature, yet fellows do also have the opportunity to build links with their peers, attend conferences and exchange knowledge. “We encourage fellows to participate in two key events: the annual ERS International Congress, which is attended by more than 20,000 people, and the ERS Lung Science Conference. The fellows receive funding to attend these events,” says Professor Belvisi. “These represent good opportunities for fellows to network, meet other researchers, present their research and share experiences.”

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A Career Development Fellowship event is held at the ERS International Congress every year, which past, current and potential fellows can all attend, while the ERS also organises many other scientific and educational activities. The wider goal is to encourage researchers to come to European institutions and tackle key challenges around respiratory diseases.

“We’re trying to attract researchers from different disciplines and retain them in Europe. A number of international researchers are coming to Europe through the RESPIRE programme and bringing their expertise, while several fellows are coming back to Europe after a period abroad, often in the USA,” says Professor Belvisi. There is also a strong focus on career development in RESPIRE2, encouraging the fellows to deepen their engagement in respiratory research. “The fellows have a scientific mentor within their host institution. We have also launched an ERS mentoring scheme, so that support and advice is provided not only in terms of their research project, but also their career development,” says Professor Belvisi.

months) and Short-Term Research & Training Fellowships (1-3 months) which fund around 65 fellows annually. “We have established partnerships with many organisations, including national societies. Recently we launched a fellowship offering opportunities in industry, while further collaborations are also in the pipeline,” she outlines. “Early stage research is really a strategic priority for the ERS. We’ve invested a lot in research, and we’re significantly expanding the opportunities we offer.”

This includes the continued development of the RESPIRE programme thanks to the next-generation RESPIRE3 which has just been awarded funding through the EU’s Horizon2020 and will be formally launched in the autumn of 2016. “We will aim to give even more choices to researchers, and we will also introduce an intra-disciplinary retreat, where the RESPIRE fellows will meet once a year amongst themselves. The idea is to foster cooperation between the fellows,” continues Professor Belvisi. This will provide more formal avenues for future

The RESPIRE programme funds early-stage research fellowships thanks to EU co-funding. The aim is to fund excellence in respiratory research and science, helping us to identify the leaders of tomorrow in the field The ERS invests significant funds in respiratory disease research, reflecting its wider public health importance. Professor Belvisi says the ERS hopes to maintain a relationship with all fellows. “We hope that the fellows will continue to be involved in respiratory research in future and to be engaged in the ERS,” she says.

The ERS also supports several fellowship programmes alongside RESPIRE2, notably Long-Term Research Fellowships (6-12

fellows to build strong support networks.

“The 2-year European fellowships could be extended to three years if – during the fellowship – the fellow and the host arrange to spend some time in industry or the non-academic sector during the third year,” she says. “So we’re providing more options to become Marie SkłodowskaCurie fellows, including travelling outside the EU and then returning through 3-year Global fellowships.”

ERS Lung Science Conference - taken at LSC2015 - Copyright@ERS.

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At a glance Full Project Title REspiratory Science Promoted by International Research Exchanges 2 (RESPIRE2) Project Objectives The RESPIRE2 programme plays an instrumental role in enabling ERS to pursue its mission to address chronic lung diseases and promote excellence in science. It provides research fellowship opportunities to post-doctoral researchers, with the potential to become the leading scientists and leaders of tomorrow in the respiratory field.

Project Funding This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no PCOFUNDGA-2012-600368.

Project Partners The ERS works in cooperation with a range of RESPIRE2 Host Centres in terms of the delivery of the RESPIRE2 programme: http://erscongress2013.org/respire Contact Details Professor Maria G. Belvisi BSc, PhD FBPhS, FERS Head, Respiratory Pharmacology Group, Pharmacology and Toxicology Section, NHLI Sir Alexander Fleming Building (SAF), South Kensington Campus Exhibition Road Imperial College London London SW7 2AZ, UK E: fellowships@ersnet.org W: http://www.ersnet.org/ers-funding/ fellowships.html

Professor Maria Belvisi

The ERS Research Director, Professor Maria Belvisi, has been appointed to oversee research activities during the period September 2013-September 2016, notably ERS Fellowships. She is an internationally recognized expert in the respiratory field with vast experience in academia and industry as well as extensive publication record.

She is currently head of the Respiratory Pharmacology group at the National Heart and Lung Institute, Imperial College, London, UK.

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A new approach to treating Parkinson’s disease Around 1.2 million Europeans live with Parkinson’s disease, and with the incidence set to rise further over the coming years in line with demographic changes, the disorder is a major research priority. Dr Yulia Sidorova and Dr Mehis Pilv tell us about the GDNF Mimetics project’s work in developing novel disease-modifying treatments against this disease A neurodegenerative disorder

that affects the central nervous system, Parkinson’s disease imposes a major burden on healthcare systems across the world, with around 1.2 million people in Europe suffering from the condition.

While treatment is available to alleviate the early symptoms, medication becomes less effective as the disease progresses, underlining the importance of the GDNF Mimetics project’s work in promoting continued research. “The project focuses on developing new treatments against the disease and training participating researchers in different fields of science,” says Dr Yulia Sidorova, the project’s Principal Investigator at the Institute of Biotechnology, University of Helsinki.

This training covers a range of areas, including animal models of Parkinson’s disease, neurochemistry, molecular modelling and physicochemical drug research methods, with the wider goal of improving treatment of Parkinson’s disease. “The project is focused on establishing close collaboration between academic and industrial researchers. We aim to promote the career development of the participants and train them in different research fields,” continues Dr Sidorova.

The project brings together researchers from the University of Helsinki and Molcode, an Estonian company specialising in computational chemistry, giving researchers a solid grounding from which to develop new treatments against

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the disease. With the elderly accounting for an ever-greater proportion of the European population, there is a growing need for improved treatment for not only Parkinson’s disease, but also other neurodegenerative conditions. “In 20 years time, it is forecast that close to 20 million people worldwide will have Parkinson’s disease and possibly 80 million people will have Alzheimer’s disease,” says Dr Mehis Pilv, the founder of Molcode. The company’s powerful

building on his close working relationships with Dr Sidorova, Professor Mart Saarma and Professor Mati Karelson. Having gained his PhD in Applied Computer Sciences in 1984, Dr Pilv has since become deeply involved in business, playing a central role in establishing both Molcode and GeneCode, an Estonian-AmericanFinnish-Dutch R&D company that develops new drug design technologies.

“There are thousands of inputs to consider in drug design and development. We have

The loss of brain dopaminergic neurons is the cause of motor symptoms in Parkinson’s disease, based on which the disease is diagnosed. However, in addition to motor symptoms, Parkinson’s disease patients also experience a number of non-motor symptoms computational chemistry tools are key to the project’s wider research agenda. “We have started to design new drugs for Parkinson’s disease, and have developed a technological platform which could also be used to develop new treatments for other neurodegenerative disorders such as Alzheimer’s disease, Hungtinton’s disease and amyotrophic lateral sclerosis (ALS), for example. We are starting to look at this potential,” says Dr Pilv.

With long experience in both the academic and commercial sectors, Dr Pilv is well placed to help translate research advances into improved treatment,

developed new artificial intelligence software systems, using elements of machine learning, to aid in the drug design process,” outlines Dr Pilv. Alongside this work, GeneCode also develops new drug candidates, targeted against several different diseases. “We have designed absolutely new, small molecule drug candidates, for the treatment of central and peripheral nervous system disorders,” continues Dr Pilv.

Parkinson’s disease The GDNF Mimetics project’s primary focus for the moment is the treatment of

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Parkinson’s disease though. While researchers are not studying the disease itself within the framework of the project, Dr Sidorova and her colleagues hold deep knowledge of the underlying nature of the disorder. “Our lab does quite a lot of fundamental research focused on the evolution, nature, progression, mechanisms and diagnostics of the disease, as well as the search for new druggable targets,” she outlines. The disease is highly complex; however, the loss of nigrostriatal dopaminergic neurons, the main source of dopamine in the central nervous system, is known to play a major role. “The loss of dopaminergic neurons is the cause of motor symptoms in Parkinson’s disease, based on which the disease is diagnosed. However, in addition to motor symptoms, Parkinson’s disease patients also experience a number of nonmotor symptoms such as problems with the gastrointestinal tract, loss of smell sensation, sexual dysfunction, emotional problems, etc.,” explains Dr Sidorova.

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There is currently no cure for the disease, and while existing methods can provide some relief from the symptoms, they also have some significant drawbacks. The current ‘gold standard’ for Parkinson’s disease therapy is the use of L-DOPA, the chemical precursor to dopamine, by which dopamine concentration in the brain can be increased. “L-DOPA can be combined with inhibitors of enzymes metabolizing L-DOPA. This treatment has side-effects and does not slow-down, stop or reverse the death of dopaminergic neurons, which is the major cause of the disease,” explains Dr Sidorova. “As the death of dopaminergic neurons in Parkinson’s disease is progressive, and less and less endogeneous dopamine is released to the putamen as the disease progresses, patients are forced to increase the dose of L-DOPA. That escalates the side-effects and limits the option to further increase the dose.”

Researchers aim to instead harness the therapeutic potential of glial cell line-

derived neurotrophic factor (GDNF), a small protein that promotes the survival of dopaminergic neurons. While GDNF has great potential for Parkinson’s disease treatment, Dr Sidorova says it is currently difficult to use it in the clinic because of its poor pharmacokinetic properties, such as its inability to cross tissue barriers.

“GDNF is a very ‘sticky’ molecule that is unable to penetrate the blood-brainbarrier,” she says. This limits its clinical applicability. “When it is injected into tissues it fails to diffuse and spread there.

So, to reach dopaminergic neurons it has to be injected directly into very specific regions of the brain,” explains Dr Sidorova. “It seems that if GDNF is injected into the putamen, where the axons of dopaminergic neurons are located, it works in animal models of Parkinson’s disease. However, it is unclear how well it is transported by neurons in patients from the injection site to the bodies of dopaminergic neurons, which are located in another part of the brain.”

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At a glance Full Project Title Small molecules activating RET for the treatment of Parkinson’s disease (GDNF MIMETICS) Project Objectives The objectives of MC IAPP project “GDNF mimetics” are to strengthen academic – industrial collaboration between University of Helsinki and Estonian SME Molcode Ltd (that is the sister company of GeneCode Ltd), that is achieved by seconding and training researchers from one partner organization to another and to develop small molecules mimetics of neurotrophic factor GDNF for the diseasemodifying treatment of Parkinson’s disease.

Project Funding Funded EU FP7 Marie Curie actions, Call identifier FP7-PEOPLE-2013-IAPP, Grant agreement no.: 612275; Parkinson’s UK Innovation Grant K-1408.

Significant supplementary funding given via GeneCode Ltd and related to GeneCode Ltd. Project Partners SME GeneCode Ltd • SME Molcode Ltd • University of Helsinki Contact Details Scientific questions: Dr Yulia Sidorova Business proposals: Dr Mehis Pilv T: ++358 504484540 E: yulia.sidorova@helsinki.fi E: mehis.pilv@gmail.com M: +372 5031801 W: www.gdnf.mimetics.eu W: www.facebook.com/gdnf.mimetics

Dr Mehis Pilv

Dr Yulia Sidorova

The aim is to replace GDNF protein with GDNF mimetics, small molecules which will be able to penetrate the blood-brain barrier. Researchers are using rational drug design methods and a range of biological techniques to develop these molecules, which Dr Sidorova says are designed to act in a similar way to GDNF. “We would like these molecules to activate the same receptors in the cells, stimulate the same intracellular events and lead to the same outcomes, namely promoting well-being and the functioning of dopaminergic neurons,” she outlines.

Ideally, researchers would like to develop drugs that can be taken orally, but if that is not possible, then Dr Sidorova says injecting the drugs, either into the vein or subcutaneously, would be a good alternative. “Injections are less convenient, but they are significantly better than the multiple stereotactic surgeries that are required for GDNF delivery into the brain,” she explains.

Drug design These drugs are designed to both prevent the death of remaining dopaminergic neurons and to restore activity in those neurons where the body is still alive, but the axons have been lost. This approach will help limit the progression of the disease and mitigate the symptoms. “This will increase dopaminergic input in the putamen and remove the behavioural symptoms of Parkinson’s disease,” outlines Dr Sidorova. Researchers are also looking

to test the efficacy of this approach, and identify ways in which it could potentially be improved. “In the early stages of the project we mostly used cell cultures to minimise the need to use animals. We screened thousands of compounds in immortalized cells lines to select a few that activated GDNF receptors. We further tested these few compounds on primary neurons isolated from rodents, and we progressed to animal models with 2-5 active molecules,” continues Dr Sidorova.

The development of novel therapies to treat Parkinson’s disease is not an easy task, but a great deal has been achieved already. Dr Sidorova and her colleagues plan to build on their success so far, pursuing further research. “We constantly seek new funding sources and partnership opportunities to continue our research,” she says. Last year, project researchers received a very prestigious award from Parkinson’s UK, which allowed them to conduct a proof of concept study for mimetics in an animal model of Parkinson’s disease, and Dr Sidorova and her colleagues are looking for further funding and partnership opportunities.

“We have attended multiple partnering events over the last few years and are looking for partners and investors to continue our work,” she says. “If our GDNF mimetics work as expected they might pave the way to the development of a completely new strategy for the management of Parkinson’s disease, and lead to a revolution in its treatment.”

Dr Yulia Sidorova received her PhD degree in Biochemistry in 2005. Afterwards se joined to the laboratory of Professor Saarma to develop small molecules mimetics of neurotrophic factor GDNF for the disease-modifying treatment of nervous system diseases. Dr Sidorova is responsible for testing of biological activity of GDNF mimetics designed by GeneCode Ltd. Dr Mehis Pilv received his PhD degree in Applied Cybernetics in 1984.

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For more information, please visit: www.euresearcher.com

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The ‘What If’s’ of EU Science Funding What dramatic geo-political effects could change everything about the European funding landscape? What if a country joins the EU? What’s the impact of a country leaving the EU? What if we slump back into global recession? How will science investment fare? We take a look at how future scenarios could play out for funding.

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orizon 2020 is historically the EU’s largest Research and Innovation programme with 79 billion euros worth of funding between 2014 – 2020. The amount of investment that scientific research wields in Europe is enormous, simply because research and innovation drives progress, whether that is saving lives, innovating industry or preserving our environment.

However, as history tells us, money dries up, money gets redistributed and power bases change like the tides. So let’s see how potential changes in the EU could affect how Europe’s science related funding might be allocated.

What if countries leave the EU? First of all – let’s ponder on the ripples from a major EU state leaving. There is a timely example we can use as a case in point. The so called ‘Brexit’, where Britain leaves the EU, is something that at the time of writing this article is hanging in the balance but by the time this feature is published, will be decided. Great Britain leaving the EU could have a variety of consequences, not least on the ability to conduct scientific research projects in the country.

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The Lords science committee in the UK raised the issue that it was unlikely that the government would replace the investment into scientific research if the country were to leave the EU and Stephen Hawking went as far to say that Brexit would spell ‘a disaster for UK science’. In practical terms the UK invested nearly £4.3 billion into EU Research projects between 2007 and 2013 and received near to £7 billion back over that period – showing clear benefits of investment. Whilst innovation and scientific research is a renowned key to harvesting long term economic rewards, the breadth of investment possible in the UK would almost certainly suffer. It would also mean the UK has less say in framework policy in Europe. It would however, potentially free up investment for science projects in remaining member states.

This is not to say the UK, or any other country in Europe leaving the partnership would not be able to collaborate and even apply for some funding but it would be a different process, which would mean potentially less influence, less involvement and ultimately, less money.

Although the UK had a choice to leave, Greece is a country that may be forced to leave the EU under the shadow of debt and the

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In practical terms the UK invested nearly £4.3 billion into EU Research projects between 2007 and 2013 and received near to £7 billion back over that period feeling in the Greek science community is pretty dark. On the Science website, Achilleas Mitsos, an economist and science policy expert at the University of the Aegean was quoted as saying, “I feel horrible…I’m really worried about science but I’m worried about my country, more than anything else.”

There are clearly grave concerns by those affected, at the prospect of leaving such a robust institution that has nursed fledgling projects from concept to fruition since the Framework Programmes came into being.

What if countries join the EU? On the other side of the coin, we come to the issue of other countries joining the EU. Is there a possibility of this occurring in the near future? Here too, we have a timely case study. Turkey has been in the spotlight for years as a contender that, with some adjustments and policy changes, could join the hallowed ranks of the Union, and in turn benefit from the investment pool. Considering that the country ranked 58th in the Global Innovation Index 2015, it has a lot to gain from the funds, collaboration and the framework that Europe can offer.

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The serious negotiations with Turkey around the possibilities of joining the EU began back in 2005. With 35 chapters of conditions set out including free movement, competition policy and justice it was clear the bar was set in terms of the changes required to qualify for membership to the European Union. To date, only one area of the EU conditions has been adopted – interestingly enough, this was for science and research, but this demonstrates clearly a process and a timescale that is dragging.

Today, with war on its borders, a refugee crisis and internal challenges, stability feels perilously brittle. Only recently there was a stirring that visa-free travel would be on the table for Turkey but hopes of this were dashed after a row over the definition of anti-terror laws and implications that they were being used unfairly to arrest journalists. What’s more, there are clear signs that Turkish President, Recep Erdogan, has lost his appetite for negotiations with EU demands in general when he said: “We’ll go our way, you go yours.” This, combined with the fact that the other member states must agree to let Turkey join (when there is opposition from some countries), means that Turkey’s accession is unlikely in the near future.

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If Turkey did join the EU – which it may well do at some distant point in the future, it would receive economic development aids and a large increase of foreign investment to drive economic growth. It could expect to receive aid similar to that which Ireland, Greece, Spain and Portugal received after the financial crisis of 2008. This investment combined with freer movement between borders would certainly court scientific research possibilities and collaborations. In reality the European Commission will likely not be accepting another country into the EU for at least five years and with current world affairs as they are, those five years could spell dramatic changes to create further delays.

What if we fall back into recession?

Having weathered a major recession we should analyse it to examine what might happen if this recurs. One significant impact on research is for non-for profit research programmes and charities outside government funding. As people have less money to spare – charity bolstered science such as those initiatives related to healthcare, can suffer. Reports in the Lancet Oncology indicated recession could mean reduced research into drug discovery during economic downturn. To take specific examples, Cancer Research UK found the financial environment of the previous recession challenging and was cautious in its spending as a result. The British Heart Foundation expressed a ‘cautious approach’ also during the crisis and Leukemia Research suffered a £13 million fall in the value of its investments during the recession.

The consequence of recession is therefore reduced investment into science by the charities, as their safeguard.

So how did scientific funding by EU countries fare during the recession? Maire Geoghegan-Quinn – European Commissioner for Research, Innovation and Science at the time, said in a 2013 performance related report covering the recession period, that: ‘the EU still lags behind major players such as the US, Japan and South Korea in terms of R&D investment relative to GDP.’ In her summary of the situation there was also a nod to the concept that it is important to ‘innovate out of a crisis’ by creating new efficiencies. It’s a noble concept but obviously, only if it works. It is recognised that industry needs more connection with research, more inter-play to drive discoveries into commercial prospects and benefits for society and no doubt there have been missed opportunities.

To show there is a gap between this kind of initial optimism and reality, in 2000 there was a bold declaration from the EU that by 2010 it would be ‘the most competitive and most dynamic knowledge-based economy in the world’ with an investment of 3% of GDP on research. The European Research and Development investment never went far beyond 2%, when it all came out in the wash. The fact a global financial meltdown was thrown into the mix shows that it’s impossible to guarantee such forecasts with accuracy.

When investing large sums into scientific research, it may feel like a tense leap into the dark. You never can predict with certainty how investigation into a challenging scientific

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territory will bear fruit. Sometimes the rewards are predictable, even world changing, sometimes they are neither.

The pressure to make money that is invested, reap financial rewards, can shadow project proposals. Whilst many will argue this is short sighted and that science needs exploring for the sake of discovery itself, in truth, when money is finite, so too will patience be if results do nothing in return to make a practical difference.

The economic landscape of Europe will have good times and bad times and whilst everyone agrees science can play a part in solutions, there are many ways to invest, especially to get out of a crisis and that is the crux of the issue of funding allocation.

This brings us to the next big question.

What if the funding is needed elsewhere?

The problem with having such as large budget for research and innovation is that it’s tempting to dip into it now and again to fund other ideas and deal with problems as they become over baring. As robust as science investment is, this is exactly what happened with the funding pot for Horizon 2020.

Perhaps the biggest threat to the EU Science and Innovation budget is the EU itself. As German Member of the European Parliament Christian Ehler said recently at a Science/Business conference: “The current Horizon 2020 budget was set in 2013 at €79 billion over seven years, a big jump from the prior seven-year plan – but that has since been chipped away as new budget priorities have appeared. National governments have plenty of distractions at the moment, chief among them coming up with a response to a surge of desperate migrants into Europe. As a result, science and

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innovation spending has fallen down the list of priorities.”

Surprisingly, back in 2014 it was newly appointed Commission President Jean-Claude Juncker who proposed diverting €2.7 billion from Horizon 2020 into a new ‘Investment Plan for Europe’, which was a controversial play at the time. “Horizon 2020 is not a lemon!

Stop squeezing it!” the League of European Research Universities (LERU) retorted in a statement after the proposal was put forward.

The Horizon 2020 initiative, as with the Framework Programmes before it, was of such importance to the European science community, that on the opening day of the process there were 70,000 forms being downloaded every hour. There is therefore a sense of concern by scientific researchers when some of the funding is seen to be diverted away.

This is not just a concern for scientists either but one for politicians. The reason that Research and Innovation is treated with such reverence is that it is perceived as a driver to Europewide economic growth, the foundations to an improved society and new industries. It is simply a way of finding solutions to the big problems and inefficiencies. In a grand sense, it is the force that ensures Europe’s relevance in the world. Strategists have to keep focused on that awkward but necessary premise that euros spent in scientific research should eventually multiply in returns.

Indeed, the whole point of Horizon 2020 is that fundamentally, it is a European wide incubator of new products and services that will safeguard Europe’s growth. The biggest ‘What if’ should be ‘What if we don’t prioritise scientific research?’. What happens then? That’s a question we probably don’t want to find out the answer to.

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Relatively little is understood about the underlying molecular mechanisms behind morphogenesis, the process by which our organs are shaped during embryogenesis. The ZEYMORPH project is using advanced imaging and genetic tools to investigate the early stages of eye morphogenesis, as Dr Florencia Cavodeassi explains

Looking at the genesis of the eye The process by

which organs and tissues are shaped during embryogenesis, known as morphogenesis, is a highly complex process which has a significant influence on the eventual function of our organs. Knowledge of morphogenesis remains relatively limited, now researchers in the ZEYMORPH project aim to shed new light on the topic. “To understand how the embryo acquires its final shape, we first need to understand not only the molecules that are involved in telling each cell in the embryo what organ it is going to make, but also how the cells are rearranged in space during this process,” explains Dr Florencia Cavodeassi, the project’s Principal Investigator.

Eye morphogenesis The project is focused primarily on eye morphogenesis, using advanced imaging and genetic tools to gain new insights into the process. Dr Cavodeassi says the cells that will form the eye are specified at an early stage of embryogenesis. “The cells that will give rise to the eyes are derived from the cells that will form the central Cellular and molecular bases of vertebrate eye morphogenesis (Zeymorph) Objectives: The global objective of Zeymorph is to elucidate the cellular and molecular events underlying the first stages of eye morphogenesis. To do so, we are exploiting the advanced imaging and embryonic manipulation techniques available in the zebrafish, in which our group has extensive training.

Dr Florencia Cavodeassi Centro de Biología Molecular Severo Ochoa (CSIC-UAM). Nicolás Cabrera 1, 28049, Madrid (Spain) T: + (0) 34 91 196 4719 E: fcavodeassi@cbm.csic.es W: http://www.cbm.uam.es/ Florencia Cavodeassi acquired extensive expertise in vertebrate neural development at UCL, London (UK), where she started to develop the conceptual basis on which her current studies are based. In 2011 she moved back to Spain to establish her group at the CBMSO, in Madrid. She currently holds a 5-year independent research position from the National Research Council (CSIC).

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Left Image: Dorsal view of the eye primordium (red) at neural plate stage (all cell membranes are labelled in green).

Right Image: lateral view of a zebrafish eye. All cell nuclei are labelled in blue and membranes in red; the anterior half of the retina is labeled in green by the expression of the _Tg{-8.0claudinb::lynGFP}zf106_ transgene. nervous system,” she outlines. Central nervous system precursors are arranged in a kind of sheet (the neural plate), before folding to make a neural tube.

There are no real morphological differences between neural plate cells at this stage, but at the onset of neural tube formation, eye cells start to move laterally and separate from the neural tube.

acquire time-lapse images,” says Dr Cavodeassi. The experimental data gathered will be analysed and integrated into a precise model of cell and tissue rearrangements, from which researchers can then look to learn more about congenital eye malformations. “With a model of the discrete steps that we think the cells take to build an eye, we can then

Once a group of cells has acquired eye fate, that group of cells starts to extensively rearrange in space. They separate from the cells that will give rise to the rest of the central nervous system, and form what we call the optic vesicles, the initial primordium of the eye “Once a group of cells has acquired eye fate, that group of cells starts to extensively rearrange in space. They separate from the cells that will give rise to the rest of the central nervous system, and form what we call the optic vesicles, the initial primordium of the eye,” explains Dr Cavodeassi.

“We think this difference in cell behaviour is triggered by the assembly of a different extra-cellular scaffold around the eye cells at that stage, as compared to what is happening in the rest of the neural tube. This scaffold is provided by a very laminin-rich, basement membrane.”

The project is using zebrafish as a model to analyse these processes. This approach offers significant advantages in terms of imaging, allowing researchers to look deep into the tissue and analyse changes around the eye primordium. “It’s relatively easy to place embryos under a microscope and

go and interrogate disease conditions, and look more closely at what is happening,” continues Dr Cavodeassi.

This research could lead to new insights into the root causes of eye malformations and visual impairment, yet Dr Cavodeassi’s primary focus remains the molecular mechanisms involved in early stage eye morphogenesis.

While researchers have learned a great deal about the cell rearrangements involved in making the optic vesicles, and the initial molecular triggers behind this process, there remains vast scope for further investigation. “We are still a long way from fully understanding the molecular network that is involved in promoting this morphogenetic transformation. We want to keep working on this, to really build a deeper understanding of the molecular mechanisms involved in this process,” outlines Dr Cavodeassi.

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Patient-specific surgical planning of an endovascular procedure designed to optimize the split of hepatic venous flow between the two lungs in a “Fontan” patient. Computational analyses performed prior to the procedure enabled to identify the optimal length of a stent-graft used to extend hepatic venous return into the main pulmonary artery. The procedure was performed according to the computations, and the following images provide a qualitative validation of our methods: The left images show a pre-operative angiogram (top) and our computer simulation (bottom) in which a clear bias of contrast towards the left pulmonary artery of the patient is observed. The right images show the post-operative scenario, in which a much more even distribution of contrast between the left and right pulmonary arteries is observed, in both the angiogram (top), and our computer simulation (bottom).

Getting the full picture of cardiovascular conditions Computational modelling of cardiovascular mechanics could greatly enhance surgical planning and help minimise the need for invasive procedures, yet there are limitations to existing techniques. Professor Alberto Figueroa tells us about his work in developing an integrated computer modelling framework, and its application in clinical settings The

traditional approach to diagnosing cardiovascular conditions still relies heavily on medical imaging and invasive measurements, now researchers are working on alternative approaches based on computer modelling. Researchers in the Integ-CV-Sim project aim to develop an integrated, image-based computer modelling framework (www.crimson. software) to simulate cardiovascular function, taking into account the key mechanisms that govern blood flow and pressure. “If you don’t incorporate the mechanisms that describe transition in blood flow and pressure in the cardiovascular system, then you don’t have a chance of actually modelling the system correctly. This is the major endeavour that we wanted to pursue in the Integ-CV-Sim project,” says Professor Alberto Figueroa, the project’s Principal Investigator.

Cardiovascular modelling The field of cardiovascular computer

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modelling is relatively young, yet a great deal of money and time has already been invested in research. However, Professor Figueroa says that so far this work has only had a limited impact in terms of clinical applications. “The first reason is that, for the most part, the simulation tools that researchers have been using are simply not up to the task. They are usually general commercial packages that are used for generic, engineering analysis,” he explains. Modelling cardiovascular blood flows requires specialist tools, while there are also other problems with existing technology.

“There’s only limited integration of physiological data in the workflow. That means the quality and the insights that you can get from the simulations is limited,” continues Professor Figueroa.

A second problem is that simulations have typically been limited to a fixed physiological state, such as a patient at a clinic undergoing a clinical assessment.

This data only provides static information.

“Your heart rate is basically fixed, you’re not going to be experiencing any physiological changes,” says Professor Figueroa. Researchers in the project aim to model what happens when the hemodynamic state changes.

“For example, when you start running, the cardiovascular system, coupled with the central nervous system, experiences a tremendous number of adjustments,” continues Professor Figueroa. “To take another example, if you suffer severe bleeding, the system dynamically responds to try and minimise that blood loss while also keeping blood pressure up.

So maintaining blood pressure and blood flow are both highly dynamic and highly modulated processes.”

The third major problem is the challenge of communication between healthcare professionals and engineers, both highly specialised fields which require a lot of training. The two career paths typically diverge at quite an early stage, and as they become more specialised, communicating

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on technical topics becomes more difficult.

“This is an issue that really poses challenges in these inter-disciplinary fields where engineers and clinicians want to work together to solve problems related to health,” says Professor Figueroa. The project aims to develop a modelling framework that addresses these three main problems, and to develop an opensource software with state-of-the-art formulations for blood flow modeling (www.crimson.software).

A key part of this work is including more patient-specific information in cardiovascular simulations. While previous simulations typically included the image of the patient, and maybe some measurements of blood flow or pressure, Professor Figueroa says it’s now possible to include much more detailed information. “Rather than relying on simple pressure and flow wave forms, we can now get highly detailed, time-resolved information on how blood vessels move. We can also get other measurements such as thickness of the blood vessel wall and other clinical metrics like pulse wave velocity or perfusion to different tissues,” he outlines.

“So the idea is, if we can incorporate all of these highly detailed metrics into the simulation framework, then the solutions will be fundamentally better and closer to the patient’s physiology.”

framework. The project has integrated several best-in-class open-source standards into the CRIMSON software, with the goal of providing a more realistic simulation of each individual patient’s physiology. “At one time SimVascular was the most advanced academic software for blood-flow modelling. With CRIMSON, we are going far beyond, and have integrated a number of best-in-class standards, including MITK, an open-source framework for medical image data and visualisation and segmentation,” explains Professor Figueroa.

“We have also integrated an open-source computer-aided design (CAD) kernel, provided by an organisation called Open Cascade, as well as Verdandi, which is a generic library for data assimilation. This library helps to automatically determine the various parameters in the model.”

This an important aspect of the project’s work, as one of the most time-consuming tasks when performing cardiovascular simulations is first obtaining the

Baroreflex

parameters of the model. Professor Figueroa says the goal is to develop a system that can automatically determine the best parameters to reproduce an individual’s data. “If we manage to do that, then we’re not going to need somebody to keep an eye on the simulation,” he outlines. A global parameter estimation module is being developed within the project, which will both help determine the relevant parameters, and address the issue of limited integration of physiological data.

“We are going to be able to incorporate a lot more information into the simulation framework. With this global parameter estimation module we will not only be able to make our simulations more realistic, but also to make the task of estimating the various parameters more systematic,” says Professor Figueroa.

This work is built on a detailed understanding of how blood flow and pressure are regulated in the body. A system called the baroreflex has overall responsibility for maintaining blood flow and pressure. “The key component of the baroreflex system is the vasomotor centre.

It is one of the most primitive parts of the brain and it controls lots of involuntary actions like breathing that you don’t even think about,” says Professor Figueroa.

Sensors called baroreceptors sense changes in blood pressure and send information to the vasomotor centre. “These sensors are connected to the vasomotor centre, which acts like a central computer and decides how things need to be changed to maintain flow and pressure. It can tell the heart to beat faster or stronger, and it can tell different regions in the vasculature of the body to relax so that the size of vessels increases, so it’s easier for blood to flow there. That has an impact on blood pressure,” continues Professor Figueroa.

Researchers aim to incorporate these main underpinning behaviours of the nervous system into the simulation

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small change, Professor Figueroa says it does affect blood pressure. “When you change your body position from lying flat on a bed to standing, there is a difference of elevation at the level of the neck of at least a metre,” he explains. The baroreflex makes a number of changes to blood flow and pressure in these circumstances, which are replicated in the simulation framework. “We have introduced some intelligence into the simulation framework so that it is able to dynamically control whatever change is introduced. It then restores initial, baseline conditions,” explains Professor Figueroa. “This system automatically predicts the changes that are needed in order to maintain and regulate blood pressure.”

This holds great importance in terms of planning medical operations, and minimising the need for invasive procedures, as illustrated by Professor Figueroa’s recent work on a very complex case. A group of clinicians got in touch with

Rather than relying on simple pressure and flow wave forms, we can now get highly detailed, time-resolved information on how blood vessels move. We can also get other measurements such as thickness of the blood vessel wall and other clinical metrics like pulse wave velocity or perfusion to different tissues

Validating the framework The simulation framework can be validated with physiological data, such as from the tilt test procedure, where a patient on a bed is raised from a horizontal to a vertical position. While this is only a

Professor Figueroa regarding a patient suffering from pulmonary arterio-venous malformations (AVMs). “They asked us to simulate different scenarios for this patient, and let them know if one scenario was more favourable than another,” he outlines.

Arterio-venous malformations are a type of abnormal connection between arteries and veins that results in reduced blood delivery to the lung microcirculation to the affected lung, the consequences of which are severe.

“This patient had a very poor hemodynamic condition. She had very high cardiac output at rest, which is terrible for the heart,” explains Professor Figueroa. “The other major problem was that she had very poor oxygen saturation in her blood, so she was always out of breath.”

The cause of these pulmonary AVMs was the uneven distribution of hepatic factors between the right and left lung.

These hepatic factors are produced by the liver, and effectively limit the uncontrolled growth of new vessels. “The right lung didn’t receive enough of these hepatic factors, and therefore started to experience the uncontrolled growth of these AVMs,” says Professor Figueroa.

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At a glance Clinicians decided to use a stent graft to funnel the flow of the hepatic factors into the area where they mix and change the distribution; the simulation framework was used to identify the ideal length and location for the stent. “We investigated what would happen if we deployed the device with different protrusion lengths in the mixing zone. We wanted to see if there was an optimum deployment length, that would give us a more even distribution of those hepatic factors, between the left and right lungs,” explains Professor Figueroa.

Researchers ran several simulations with different stent lengths, looking for an even distribution of hepatic factors between the left and right lung. Through these simulations, researchers were able to identify the optimal length of the stent.

“The optimal stent deployment length was the 22.5 mm. That led to a more even distribution of the hepatic factors,” says Professor Figueroa. These simulations also revealed important insights into the distribution of hepatic factors under other stent lengths. “It’s important to note here that if a stent is deployed without any thought about the ideal length, you might end up doing a procedure which leads to performance which is just as bad as the

pre-operative case,” continues Professor Figueroa. “The 30mm protrusion length for example gives you effectively the same performance as the pre-operative case, with a very biased distribution of hepatic factors. That wouldn’t help the patient.”

The project team were able to advise the surgical team on the length of the stent before the operation, from which they also gained important insights into the accuracy of the simulation framework.

Researchers asked the surgical team to take both pre- and post-operative angiograms, to verify whether the simulations were correct; Professor Figueroa says the results were clear. “This was the first time where we very clearly demonstrated that our blood flow simulation framework has the ability to be predictive,” he says. This holds great potential in terms of surgical planning and minimising the need for invasive procedures. “Sometimes a procedure needs to be invasive, but there are many ways of doing it wrong, and potentially there’s only one way of doing it right,” points out Professor Figueroa. “The devil is in the detail – in the case I described the length of the device – and that might make all the difference to the success of an operation.”

Drs Christopher Arthurs (sitting) and Miguel Vieira (standing) discuss the computational results of a congenital patient with pulmonary hypertension at St Thomas’ Hospital. Dr Vieira is a Cardiologist at the Evelina Children’s Hospital in London and also a PhD student in this ERC-funded project. Dr. Arthurs, a mathematician also working on the project, develops formulations in which complex boundary conditions for blood flow modeling can be applied in a graphical and intuitive manner by clinical fellows.

Full Project Title An Integrated Computer Modelling Framework for Subject-Specific Cardiovascular Simulation: Applications to Disease Research, Treatment Planning, and Medical Device Design (INTEG-CV-SIM) Project Objectives Despite great initial promise, the actual use of patient-specific computer modelling in the clinic has been very limited, mostly due to cumbersome, inadequate modeling tools. In this project, our teams is developing an integrated image-based computer modelling framework for subject-specific cardiovascular simulation (www.crimson.software), which combines state-of-the art formulations for large-scale blood flow modeling with an easy-to-use, intuitive interface that can facilitate the use of the software by individuals with clinical backgrounds. In the course of the project, 5 clinical fellows (cardiac surgeons, vascular surgeons, and cardiologists) have been trained in the use of the CRIMSON software.

Project Funding • United States National Institutes of Health • T he Royal College of Surgeons of England Research Fellowship • Wellcome Trust • Heart Research UK Contact Details Professor Carlos Alberto Figueroa Alvarez North Campus Research Complex B20 211W, 2800 Plymouth Road, Ann Arbor, MI 48109-2800 USA T: +1 734 763 8680 E: figueroc@med.umich.edu W: www.crimson.software

Professor Alberto Figueroa

Born and raised in A Coruña, Galicia, Spain, Figueroa attended the local university where he studied numerical methods and fluid mechanics. After completing his B.S. and M.S. in Civil Engineering, Figueroa enrolled in a PhD program in Mechanical Engineering at Stanford University, where he developed computational methods to simulate how blood flows within elastic models of arteries built from medical images such as MRI and CT. In 2011, Figueroa joined the Department of Biomedical Engineering faculty at King’s College London as Senior Lecturer.

In 2014, Figueroa joined the University of Michigan faculty as the inaugural Edward B. Diethrich Associate Professor of Biomedical Engineering and Vascular Surgery.

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Droplet Microarray –

miniaturizing biological experiments Cell screening is central to the development of new drugs and also holds growing relevance to personalized medicine, yet current methods have some significant limitations. We spoke to Dr Simon Widmaier and Dr Anna Popova about their achievements in Aquarray, a project dedicated to developing a new platform for high-throughput screening experiments on biological cells High-throughput screening (HTS) approaches play a crucial role in identifying effective treatments for literally all diseases.

High-throughput screening campaigns are used to perform and evaluate hundreds of thousands biological experiments in parallel every day, yet current methods have significant limitations. Researchers in the ERC-backed DropCellArray project, based at the Karlsruhe Institute of Technology (KIT) in Germany, have developed novel platforms for cost-effective HTS experiments. “Our goal is to commercialize novel solutions for miniaturized biological experiments via our spin-off company Aquarray,” says Dr Anna Popova, a post-doctoral researcher in the laboratory of Dr Pavel Levkin, the project’s Principal Investigator.

The DropCellArray project itself is developing an innovative platform for cell experiments based on the use of superhydrophilic micro-arrays, which have a strong affinity to water, separated by superhydrophobic, water-repellent barriers.

These differences in affinity to water can be used to create high-density arrays of microdroplets. “We create patterns of superhydrophilic and superhydrophobic

Cell-based screenings Most cell-based screening experiments are currently performed in microplates (or microtiter plates), yet Dr Popova says that the techniques currently used for HTS are relatively inefficient. “Big pharmaceutical companies typically screen over 100,000 compounds a day, so a lot of microplates and large reagent volumes are required,” she outlines. Cell compatibility and cost are also major concerns to pharmaceutical companies and academic laboratories, where many cellbased screenings are performed. “Currently, consumables account for around 75 percent of the cost of HTS to pharmaceutical companies. By downscaling screening experiments, you can invest the consumables more efficiently,” says Dr Simon Widmaier.

Dr Widmaier is currently involved in the foundation of Aquarray, a start-up company building on earlier research findings, and the commercialization of the technology within the ERC-PoC CellScreenChip project.

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The Aquarray team (from left to right): Professor Jörg Vienken, Dr. Pavel Levkin, Dr Anna Popova, Dr Gunter Festel, Dr Simon Widmaier and Konstantin Demir (not included in the image Professor Marcus Textor and Professor Michael Grunze) areas on the surface of biomaterials, which serve as a platform technology. Due to the high difference in the wettability of these two areas, the application of an aqueous solution on top of the surface leads to the spontaneous formation of microdroplets,” explains Dr Popova.

Each of these droplets in the so-called Droplet Microarray (DMA) can then serve as a micro-reservoir for culturing cells.

With the DMA technology, at least 95 percent of reagents can be saved, compared to even the best microtiter plates available in the market today. Dr Popova showed in earlier research that cells can be grown in these droplets, and in fact that they proliferate.

Drug discovery and 3D cell culture applications The wider goal in this research is to help accelerate the process of drug discovery.

More and more chemical compounds are available today as potential drug candidates, building on recent research advances. “Combinatorial approaches have matured over the last decade, and also there are more approaches from the biochemical side, particularly when it comes to nucleic acids,” says Dr Widmaier.

Cell screening technology must also develop and become more efficient if this is to lead to the development of new medicinal drugs.

The development of 3D cell cultures holds clear potential in these terms. 3D cell cultures have emerged as realistic in vivo like models for cell-based in vitro assays, which represent the complexity of a living organism more closely than alternatives. The research of Dr Levkin’s group shows that the DMA platform can be used to produce large quantities of socalled spheroid 3D cell aggregates, based on a hanging droplet approach. This opens up new opportunities to use hydrogel microarrays on the DMA for spheroid and organoid production and screenings, in addition to their established functionality in producing 3D cell cultures. A patent application has recently been filed for this invention, looking to capitalise on its wider potential.

Aquarray The project’s results are not limited to one specific sector though, and in fact hold relevance to all areas of life sciences research. Now the team is intensifying its work on Aquarray, as part of the

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Aquarray’s Product Platform I consisting of the Droplet Microarray (DMA), a Library Microarray (LMA) and a holding device for parallel alignment.

At a glance Full Project Title DropletMicroarrays: Ultra HighThroughput Screening of Cells in 3D Microenvironments (DropCellArray) Project Objectives The project aims to develop a new platform for HT cell screening experiments using the unique properties of the superhydrophilic microarrays separated by superhydrophobic thin barriers. The new technology will allow us to perform up to 300,000 cell experiments in parallel using a single chip.

Project Funding ERC Starting Grant 2013, 1,499,820 Euros.

EU projects DropCellArray project (Activity Code: ERC-SG-PE8) CellScreenChip project (ERC-2015-PoC DLV-680913)

CellScreenChip project’s work in translating research advances into practical applications.

Aquarray is located at the KIT Hightech Incubator in the National Research Centre of the Helmholtz Association. This allows Aquarray researchers access to the first class infrastructure of KIT, and the team collaborates closely with the KIT technology transfer unit IMA. The founders team is supported by an international advisory board, combining research and commercial expertise,

results, the team’s professional expertise and recent patent applications. “We have developed two product platforms which open new screening opportunities to research areas, all the way from basic biological research over industrial ultrahigh-throughput screening (uHTS) to diagnostic and clinical applications,” says Dr Widmaier. One product platform has been optimized for manual operation in a basic research, diagnostic or clinical context to achieve high throughputs at low initial cost.

Contact Details Dr Pavel Levkin Chemical Engineering of Biofunctional Materials Group Institute of Toxicology and Genetics Karlsruhe Institute of Technology Hermann-von-Helmholtz Pl. 1 76344 Eggenstein-Leopoldshafen T: +49-721608-29175 E: levkin@kit.edu W: www.levkingroup.com W: www.facebook.com/pavel.levkin W: https://twitter.com/levkinlab W: www.aquarray.de

Dr Pavel Levkin

Aquarray develops the Droplet Microarray (DMA) technology platform for miniaturized high-throughput and

pipetting-free biological screening experiments as well as solutions for increasing laboratory efficiency, reducing screening costs and scaling the research throughput bringing together highly qualified specialists with business advisors and experienced entrepreneurs, as well as cell biologists, biophysicists and chemists. The team holds deep expertise in surface chemistry, molecular biology, and laboratory methods. With the advisory board’s combined experience in business development, the team is well-placed to develop new products which meet both academic and commercial needs.

Several product packages have been developed so far, based on research

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Another product platform is designed for automation and ultra-high throughput campaigns in an industrial R&D context.

Aquarray offers training and services to integrate the product packages into existing screening workflows. The founders’ team envisages delivering system solutions for miniaturized biological screenings which are more applicable and yet cost-effective for future applications, ranging from basic biological research over industrial uHTS to diagnostics and personalized medicine.

Dr Pavel Levkin is the Independent Leader of the Biofunctional Polymer Materials group at the Karlsruhe Institut fur Technologie. His main research interests are organic and polymer chemistry; biofunctional materials, surfaces and nanoparticles; surface functionalization and patterning, and superwettability.

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The therapeutic potential of nanomedicines has attracted a great deal of interest, yet technical challenges remain before they can be more widely applied in clinical settings. Dr Philipp Seib tells us about the NanoTrac project’s work in both developing silk-based nanoparticles, which are intended to act as drug carriers, and in investigating the body’s response to this form of treatment

A new path to targeted treatment Research into nanomedicines could eventually lead to significant improvements over current methods of treating disease. Dr Phillip Seib of the NanoTrac project points to cancer as an example.

“With conventional chemotherapy, if a patient is injected with an anticancer drug, then essentially that drug is distributed in tissues throughout the body - not just the tumour tissue, but also healthy tissue.

That causes significant side-effects, and limits how much of the drug you can give to a patient,” he explains.

By contrast, nanomedicines could be targeted much more precisely to the tumour tissue by exploiting disease pathology. When anticancer agents are introduced into the body using nanoparticles or macromolecular drug carriers, the distribution of the anticancer agent changes.

“The anticancer agent now is delivered with the aid of a nanoparticle. And if you inject those, they aren’t distributed in all tissues, but seek out the solid tumour,” Tracing the Intracellular Fate of Anticancer Nanomedicines (NanoTrac) Dr Philipp Seib Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde 161 Cathedral Street Glasgow G4 0RE United Kingdom T: +44 (0) 141 548 2510 E: philipp.seib@strath.ac.uk W: http://www.seiblab.com W: http://cordis.europa.eu/ project/rcn/107142_en.html

Dr Philipp Seib obtained his BPham and MSc from King’s College London and his PhD in drug delivery from Cardiff University before undertaking postdoctoral research at the Technical University Dresden (Germany) and Tufts University (Boston, USA). He took up his position as lecturer in Cellular Pharmaceutics at the Strathclyde Institute of Pharmacy and Biomedical Sciences in November 2012. His research interest lies at the interface of cell biology and drug delivery with a specific focus on engineered cellular microenvironments.

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says Dr Seib. Based at the University of Strathclyde in the UK, Dr Seib and his colleagues are investigating the fate of nanoparticles at the body, tissue, cellular and subcellular levels. “The use of nanomedicines is one way to spare healthy tissue from the toxic effects of anticancer agents. Indeed, a better understanding of these nanomedicines will open up opportunities to deliver drugs to specific locations within a target cell,” he says.

Silk nanoparticles A number of questions remain about how these nanomedicines should be delivered into the body however. Researchers in the NanoTrac project have developed silkbased nanoparticles which hold clear potential in these terms. “We reverseengineer silk, and then we generate silkbased particles,” says Dr Seib. The project is investigating the potential of these nanoparticles to act as a drug delivery system, with researchers applying ‘stealth’ design principles to help them evade the immune system. “One of the big problems is that typically if you just generate nanoparticles and inject them into the

bloodstream, immune cells are immediately going to recognise them.

Therefore you need to hide them,” explains Dr Seib.

Researchers have grafted polyethylene glycol to the surface of these nanoparticles to help them evade the immune system, and are continuing to investigate their therapeutic potential.

These particles can be loaded with several agents to treat disease; anticancer therapy is an area of particular interest to Dr Seib and his colleagues. “We’ve loaded the particles with two anticancer agents,” he says. These silk nanoparticles could potentially also be used to deliver other types of medicines; Dr Seib says it’s important to first verify their biocompatibility and impact on cellular responses, such as blood compatibility, metabolomics and intracellular fate.

“We’ve taken these nanoparticles, and we’ve subjected them to biocompatibility testing, asking questions around how they interact and impact the biology of various cell types, including intracellular trafficking,” he outlines.

There is great enthusiasm around the development of nanomedicines, but they need to be rigorously characterised before they can be used in clinical settings.

The standard approach currently is to put cells in tissue culture, then grow them, treat them and draw conclusions about the biology; the project aims to develop sophisticated new model systems to assess nanomedicines. “We’re trying to move away from standard methods, to develop culture systems that more closely reflect what really happens in our body,” says Dr Seib. Researchers plan to continue this work in future, building foundations for the continued development of nanomedicines. “We want to further refine the cell culture models, and to probe deeper into the biology. How do cells respond to these kinds of treatments?” says Dr Seib.

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The physical and chemical properties of a material’s surface have an important influence on the way it interacts with the environment. Researchers in the POMCAPS project aim to create macro-porous solid materials with well-controlled pore morphologies and specific modifications of the pore surfaces, as Principal Investigator Dr Wiebke Drenckhan explains

Beneath the surface of porous materials Porous materials are

heavily used across a wide range of applications. The presence of gas pores (Figure 1) provides these materials with complex mechanical, thermal and acoustic properties, while they are also lightweight and offer large surface-to-volume ratios. For many applications, including catalysis, filtering, tissue engineering and heat exchange, the surface properties of the pores are of great importance.

A great deal of research attention has therefore centred on developing methods to modify these surfaces in a controlled way. With no straightforward technique currently available to homogeneously modify the surfaces inside complex materials like macro-porous solids, researchers in the ERC-backed POMCAPS project are using a bottom-up approach to tackle the problem. “The aim of the project is to develop methods which allow controlled surface modifications in-situ during the generation of the porous materials,” explains Dr Wiebke Drenckhan, the project’s Principal Investigator.

The standard approach currently is to first make the porous material, then modify the pore surfaces afterwards.

However, Dr Drenckhan says it is difficult to access the surfaces within the material with this method, so the project is developing an alternative approach. “Our approach will allow us to simultaneously control the size distribution and the organisation of the pores (Figure 1)

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Figure 1: The POMCAPS project aims to bring order into porous materials such as polymer foams. together with their surface properties, so that we won’t have to modify the porous material afterwards,” she explains.

The surfaces inside the porous material can have important implications for its overall properties. Surface properties play an important role in fluid transport through a porous material; Dr Drenckhan points to a sponge by way of example.

“When you look at a sponge you have pores of different sizes which control how much water can be taken up and how easily. So the first part of our research is really about controlling the size and the

organisation of these pores, and also whether they are connected or not. Then, if you can imagine walking through a sponge, we want to control the surface properties of all the solid surfaces that you see,” she continues. “For example, some materials hate water and some materials love water. We want to be able to change these surface properties between something that loves water and something that hates water – but we also want to go a step further. For example, we want to make surfaces which are quite rough or have polymeric hairs sticking out.”

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Self-organisation on two levels This work exploits detailed research into the physics of ‘self-ordering’ at two length scales (Figure 3): that of the pores and that of the pore surfaces. The pores themselves are typically around 100 micrometers in diameter. “We master this length scale by using well-controlled liquid templates which are then solidified to give the final porous solid. To generate the templates we use purpose-designed microfluidic techniques in which the different liquids and the gas travel through a newtork of small channels in order to produce equal-volume bubbles (Figure 4).

These bubbles are then put into containers with certain geometric properties where they organise spontaneously into highly periodic foams. This organisation is done by physics and governed by strict physical rules. This is what we mean by self-ordered systems. A lot of this part of our research is about trying to understand the physics around question 5 like: How do the bubbles organise in space?

What mechanisms control their final geometry?” outlines Dr Drenckhan.

One of the key problems researchers need to tackle is ensuring the stability of the foam templates. If two bare bubbles are brought together, they will just coalesce and form a bigger bubble, something which needs to be avoided when developing the foam. “The way to avoid it is by putting stabilising agents at the bubble surfaces,” explains Dr Drenckhan. “Many different substances can be used for this purpose. We can use classic soap-like molecules, but they are not very efficient. Today we know how to modify small particles, so that they act like a giant soap molecule leading to outstanding foam stability. We can also use polymers or certain proteins,” she outlines. These stabilising agents are always present in foams, such as in the milk on your coffee, or like you might find after using shampoo in the bathroom.

The stability of the foam derives from

Figure 2: Upon solidification of an initially liquid foam template the thin films which separate neighbouring bubbles can either remain in place or break, modifiying greatly the material’s properties. the fact that these agents go to the interface. “So if you imagine a bubble, these agents sit on their surface where they form a protective armour and ensure stability,” explains Dr Drenckhan. Once these agents are at the surface of the bubble, they organise in a certain way, which is again governed by physical principles; this all happens naturally.

“This is the second level of selforganisation – this time at a nano-metric scale,” says Dr Drenckhan.

While in these examples the stabilising agents are used primarily to stabilise the liquid foam, Dr Drenckhan’s project aims to use their presence for a wider purpose. “We want to make sure that these agents stay at the bubble surface – which will become the surface of the pore. Once the template is solidified, this modifies the surfaces of the pores, which depends on the nature of the stabilising agent,” she explains.

These agents all have certain chemical properties which they confer to the surface of the pore. Larger agents, like particles or polymers, can provide the surface with a surface roughness or a polymer ‘carpet’.

Figure 3: The POMCAPS project exploits self-organisation at two length scales: that of the stabilising agents and that of the bubbles.

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The advantage of the microfluidic approach is not only that it can be used to generate equal-volume bubbles, but researchers can also integrate complex chemical processes into a complete ‘Lab-ona-Chip’ (Figure 4) in such a way that they are the same for each bubble. Hence, the surface modification of each pore should be identical.

The project therefore profits from selforganisation at two length scales. “We let the bubbles organise on the macroscopic scales, and on the surface of each bubble the stabilising agents self-organise on a nanoscopic scale,” says Dr Drenckhan.

“The physics of these two length scales is very different. One is governed by fluid mechanics, while the other is governed by thermodynamics. But as part of the project’s work we let them come together.”

Researchers also exploit emulsions, foamlike liquid / liquid mixtures in which the bubbles have been replaced by drops, in much the same way, before they are then solidified.

The use of emulsions provides some additional handles on the generation process and the final properties of the material.

Porous materials These insights are highly valuable in terms of the project’s work in generating and characterising porous materials. The project’s approach generates a solid foam in which all of the pores are the same size, now Dr Drenckhan and her colleagues plan to pursue further fundamental research, aiming to build a deeper understanding of porous solids.

Links have been established with industry, as researchers look to address further key questions.

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At a glance Full Project Title Self-organisation at two length-scales: generation and characterisation of porous materials with chemically and physically modified surfaces (POMCAPS)

Figure 4: Bubbles are generated and chemically treated in a Microfluidic Lab-on-a-Chip.

“In order to advance with the project, we need to develop certain types of devices that allow us to do further characterisations adapted to our questions.

Researchers are working with the commercial sector to develop such devices.

One important question is around understanding the thin films that separate bubbles,” outlines Dr Drenckhan.

“If I want liquid to flow through my porous material, these films need to break during solidification in order to create an

The long-term goal is to optimise the porous materials for specific applications.

The current focus however is more on fundamental research, with Dr Drenckhan looking to investigate further questions around the behaviour and properties of porous materials. “We are looking at the mechanical and acoustic properties of porous materials; we also want to look at how liquid moves through them, or how cells or bacteria may grow in the matrix,” she says.

We know how to modify small particles, so that they act just like a soap molecule. They go to the interface, and stabilise the foam or emulsion. We can also use polymers or certain proteins interconnected pore network (Figure 2).

However, if the films break too early, the foam collapses. This tuning requires a good understanding and control of the stability of thin films before and during solidification. We still need to acquire this understanding – and we need appropriately designed characterisation tools for this,” says Dr Drenckhan.

“We also work with companies that make custom-designed molecules, as we have to think carefully about the kind of agents that we put at the interfaces. They have to be designed in such a way that they want to go to the interface, that they react with the matrix, that they stay there when it is solidified, and that they confer the desired properties to the pore surface. So there are a lot of chemical details to consider.”

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The ERC grant is well-suited to this kind of fundamental, inter-disciplinary research. “With an ERC grant, you can really dare to ask fundamental questions and to tackle high risk projects. I’m a physicist, and have entered far into the field of physical chemistry and chemistry in this project, in a way which I would have never dared without such a solid and longterm funding stream, since it is difficult to know when the project will start to bear its first fruits. We have to learn many new things, and be ready to make mistakes – this can be scary but it is also what makes such projects exciting,” says Dr Drenckhan. “With an ERC grant you can do that, because you have five years where you can really solidly advance on a subject.”

Project Objectives Recent advances in Soft Matter physics have revealed the extraordinary properties of surfaces with complex physico-chemical modifications. Of particular interest is the influence of such modifications on the wetting and flow of simple or complex fluids through macro-porous solids.

However, a deeper understanding remains out of reach, due to the difficulty of creating reliably such kind of macroporous materials.

The POMCAPS project therefore proposes to develop an original bottom-up approach which solidifies well-controlled liquid foam or emulsion templates. The approach relies on self-organisation at two length scales in the initially liquid template : that of the pores (drops or bubbles), and that of interfacially active agents (polymers, particles) at the surface of the pores.

Contact Details Principal Investigator, Dr Wiebke Drenckhan Laboratoire de Physique des Solides Université Paris-Sud - UMR 8502 Bâtiment 510 91405 Orsay Cedex T: +0033 (0)1 69155327 E: drenckhan@lps.u-psud.fr W: www.lps.u-psud.fr

Dr Wiebke Drenckhan

Dr Wiebke Drenckhan is a CNRS researcher at the Laboratoire Physique des Solides (Orsay) and the Institut Charles Sadrons (Strasbourg). She gained her PhD from Trinity College, Dublin, in 2004. Her main research interests are the properties of dispersed systems, such as foams and emulsions in the liquid or solid state.

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The recent discovery of the Chiral Induced Spin Selectivity (CISS) Effect marks a new stage in our understanding of how electrons travel through chiral molecules. This opens up new possibilities in the application of chiral molecules, and could also lead to new insights into electron transfer processes in biological systems, as Professor Ron Naaman explains

Unravelling the secrets of the CISS effect The recent discovery

of the Chiral Induced Spin Selectivity (CISS) effect, where researchers found that electron transmission yield through chiral molecules depends on the spin orientation of the electron, opens up a range of research opportunities. Based at the Weizmann Institute of Science in Israel, Professor Ron Naaman is the Principal Investigator of the CISS project, an initiative which is investigating the effect, building on existing knowledge of biomolecules. “All biomolecules have what is called a chiral (hand in Greek) character.

Namely there are two types of molecules with exactly the same chemical properties; however, they are a mirror image of each other. In biology, molecules have a specific type of chirality, and that’s why the

Above: (a) Scheme of the device and of the four-probe measurement. The Au/SAM/Al2O3/Ni device is constructed on a Si/SiOx substrate. The chiral SAM/ Al2O3 tunneling barrier polarizes the spin distribution of transmitted electrons, and it is probed by the magnetic field dependence of the resistivity through the Ni layer. (b) A SEM image (top view) of the device with a thin (1 micrometer wide) gold trace and a wide (50 micrometer) nickel trace perpendicular to it.

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electron transfer properties through these molecules are so important,” he outlines.

The CISS effect relates to how electrons travel through these chiral molecules.

“Electrons have two key properties: one is that they are negatively charged, and the second is spin. You can think about it as electrons rotating clockwise or counter-

significant impact on many fields of research, including biology. “In biology, it’s known that electron transfer is very efficient over relatively long distances. The question was why? Now that we understand it better we know that it’s related to the CISS effect,” says Professor Naaman.

Researchers have established that because

We’ve found that where electrons go through chiral molecules, one state of spin is preferred over the other. That’s very interesting, because typically you get this spin selection only with ferromagnetic materials clockwise – these are the two states of the spin,” continues Professor Naaman.

“We’ve found that where electrons go through chiral molecules, one state of spin is preferred over the other. That’s very interesting, because typically you get this spin selection only with ferromagnetic materials. Chiral molecules are not a magnetic material, yet still only one state of spin can be transmitted through them.”

A combination of experimental methods are being used in the project to investigate the CISS effect, including photoelectron spectroscopy, single molecule conduction and spin-specific conduction. One initial goal was to establish the parameters that affect the magnitude of the CISS effect.

“One key parameter is of course the molecular length. If we think of chiral molecules as a helix (coil) other parameters that affect the CISS effect are the radius of the coil and its pitch,” explains Professor Naaman. This work is combined with investigating the role of the CISS effect in electron transfer in biology-related systems. “We tried to understand, first of all, to what extent spin polarization helps in electron transfer and makes it more efficient,” says Professor Naaman.

The project is both pursuing fundamental research into the CISS effect and also exploring potential commercial applications. This work is set to have a

one state of spin is preferred over the other, the electron can move over longer distances. “Think about a bullet after it’s been fired out of a rifle – because it rotates, that bullet moves forward in a more stable way and for a longer time than if it doesn’t rotate,” explains Professor Naaman.

A model describing electron transport through chiral molecules. A centripetal force is acting on the electron keeping it bound to the molecule.

In the rest frame of the electron this force is represented as a magnetic field acting along the axis of the molecule. This effective magnetic field is responsible to the spin selectivity of the electron transmission.

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Industrial applications These findings hold real importance in terms of potential industrial applications.

The CISS effect represents a change in the established paradigm, opening up innovative new approaches to technical development. “We can make electronics where, instead of measuring the charge of the electrons, we measure the spin of them. The advantage there is that we can make electronic devices which consume less energy,” explains Professor Naaman.

This field of technology is called spintronics; previously researchers had to use magnetic materials to define and to measure the electrons’ spin in spintronics devices. The project’s research will result in the establishment of chiral organic molecules as a new substrate for spintronics applications. “We are building devices that, instead of using ferromagnets – which are complicated and difficult to handle – use chiral molecules. So we can change the material,” continues Professor Naaman.

The use of chiral molecules could make it much easier to produce spin valve devices, which are used in all hard discs.

These devices could be made much smaller with chiral molecules, which Professor Naaman believes will bring some significant benefits. “The advantage will be that we can read information on the hard disc at a much higher resolution, which means we can put more information per area,” he says. This holds real importance given the trend towards miniaturisation in the technology sector, and consumer demand for ever-higher levels of performance, underlining the wider relevance of the project’s work.

There are also other potential industrial applications for this research. For example, many people have tried to artifically produce hydrogen as a means of generating energy, but Professor Naaman says there is room for improvement in this regard. “So far, efforts to artificially produce hydrogen have been very inefficient, but it’s not clear why,” he outlines. Researchers have found that if they can control the process in which electrons are transferred in such a way that only one spin state is transferred, then efficiency improves dramatically, while Professor Naaman says there are many other implications arising from the project’s work. “We have also observed that when electrons are transferred in photosynthesis for example, only one spin is transferred,” he outlines.

This work in investigating the role of the CISS effect in biology will form an important part of Professor Naaman’s future research agenda. Along with establishing the role of the CISS effect in biology, Professor Naaman is also looking towards further development of specific devices. “We are trying to build different devices, such as magnetic memory devices and spin filter devices, that are based on the CISS effect,” he says. This work is of real interest to the commercial sector, in particular high-tech industries, and their feedback is helping to guide the project’s research. “There is feedback from industry – we are in contact with several companies, and we are trying to respond to the needs of industry,” says Professor Naaman.

Figure Above: Panel (a) shows a schematic diagram that illustrates the electrochemistry setup, in which a gold-coated Ni film is the working electrode (WE), a platinum wire is the counter electrode (CE), and a Saturated Calomel Electrode (SCE) is the reference (RE) electrode. The Ni electrode is magnetized with an external magnetic field (H) that is applied by placing a permanent magnet below the Ni electrode, with its magnetic dipole pointing up or down (white and yellow arrows, respectively). Panel (b) illustrates the protocol for covalently tethering TBO to the working electrode via a cysteine (L or D) linker. Panel (c) illustrates the protocol for preparing a mixed monolayer of 11-mercaptoundecanoic acid and 1-octanethiol and immobilizing cytochrome c on it.

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At a glance Full Project Title Chiral Induced Spin Selectivity (CISS) Project Objectives 1. Verifying the parameters that affect the spin selectivity of electrons transport through chiral molecules.

2. Constructing spintronics devices that are based on the CISS effect 3. Investigating the role of the effect in electron transfer through biomolecules and bio-systems.

Project Funding The research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement n° 338720.

Contact Details Professor Ron Naaman Chemical Physics Weizmann Institute of Science Rehovot 7610010, Israel T: +972(0)8 934 2367 E: ron.naaman@weizmann.ac.il W: http://www.weizmann.ac.il/ chemphys/naaman/

Professor Ron Naaman

Professor Ron Naaman is a full Professor in the Department of Chemical Physics at the Weizmann Institute of Science. A Fellow of the American Physical Society. Ron Naaman was a Postdoctoral Fellow at Stanford University in California before moving on to becoming a lecturer and research associate at Harvard. His research and lecturing activities then took him to Weizmann as well as visiting positions at the Joint Institute for Laboratory Astrophysics (JILA) at Boulder Colorado, the University of Pittsburg, University of California Santa Barbara, EPFL in Lausanne Switzerland, and the Technical University in Dresden, Germany. Ron Naaman main research interests are in electronic properties of nano devices and interfaces.

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Britain and EU in limbo – what will happen next?

The European Union has had the biggest shake up since its conception. The UK, one of the big three wealthiest nations in the EU (the other two being France and Germany), is divorcing from the relationship. It has been a shockwave that has rippled through the UK, split up its political parties, threatened a second Scottish referendum, pitting many people in the country against each other in opinion and pulled the rug from under Europe. The shockwaves have rippled around the world. We look at how the vote could affect both science and business and what the future may look like

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or those who woke up on the Friday of 24th June in Britain – the morning after the votes had been counted in the referendum, there was a sense of disbelief. Even many of those who voted ‘leave’ have since said they were surprised – as it had always been presumed by many media commentators and pundits we would remain. Indeed, there seemed very little logic to leave and yet there was a powerful undercurrent of disgruntled people, many older, many listening to messages from the Leave camp about immigration flooding the country, about how the UK had a chance to ‘take back control’. After emotional podium battles broadcast on British TV, complete with accusations of racism, lies, misinformation and misunderstanding what the EU even was, Brexit became very real.

Discord ensues Since then, divisions and upset have been standard daily news.

The Labour party, the opposition party to Conservatives, has

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fragmented as their leader Jeremy Corbyn has been blamed for not campaigning hard enough to stay in Europe. Boris Johnson, the leader of the Leave campaign, having won, has decided not to run for PM. Johnson’s departure was seen as something of a betrayal by many Leave campaigners. And all this after David Cameron said he would step down – effectively creating a scrum for his chair.

Meanwhile, there is a marked division in the country – with the 48% Remain voters venting anger at the situation, some still intent on fighting the result. There have also been reports of racism and hate crime – due to an unpleasant element of Leave voters, since the result. Scotland may attempt to split by holding its own second referendum and the United Kingdom is now anything but united in any way. We have to ask, is it all ‘doom and gloom’ for the foreseeable future or is this all simply shock, a moment in history that we will collectively look back on one day as little more than a sea-change in the structure of things?

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Meanwhile, there is a marked division in the country – with the 48% Remain voters venting anger at the situation, some still intent on fighting the result

For now, the only question we are all asking is what will happen next, as leaders chop and change on a daily basis in Great Britain.

The truth is no one knows or what happens next. Everything has changed so fast that the shockwaves to our geopolitical landscape, financial environment, culture and well – everything, looks a bit different.

Once Article 50, the big red ‘exit’ button, is triggered there is a two year period to negotiate the details of the new relationship.

If during this time, negotiations have not been concluded then the UK reverts to World Trade Organisation trade rules. This would mean the UK would face tariffs on all the goods it sells to the EU. Processes aside – the UK will be eager to test negotiations back with the EU Of course exports to the UK are enormous from Europe – and Britain has always been a pillar of the EU, so the remaining member states have a huge stake in renegotiations. Great Britain is the EU’s greatest trading partner. How EU companies react to any changes in trade deals will be critical for all economic outcomes.

The biggest problem for a good Brexit deal is around free movement of citizens in the EU. Free movement is the ‘big one’. It is what Brexiters want to stop but is a precondition of access to the single market.

We can make a few predictions and speculations and that is what analysts, journalists, think tanks, official bodies and universities have been doing. Here are a few views and insights from informed people and sources who are thinking about the implications.

Research challenges Science will almost certainly suffer some consequences from the Brexit. Pallab Ghosh, BBC science correspondent said in the news programme, Outside Source: “With EU membership UK science did incredibly well – it got about a billion pounds each year which is ten percent of all the money the universities get. The concern is, with Brexit, that all that could go away and leave a huge gap in research funding but also all the collaborations that scientists need to work at the cutting edge of their fields, that could also go as well…”

As everyone that features their projects in this publication will know, scientists from around Europe need to collaborate closely to do their research. What’s more, UK universities employ 30,000 EU scientists. Freedom of movement means that the best EU scientists are attracted to go to the UK to work. The EU stipulate that free movement is necessary to qualify for funding, but that

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is what Leave voters were fighting against. ‘Brain-exit’ is a term that has been used as scientists warn that without access to a single market we’ll lose the ability to entwine leading scientists effectively on projects not just in the UK but throughout Europe.

Brexit supporters want to focus on opportunities from places like the US, China and South Korea. How these countries will react to Britain’s new status remains to be tested.

Between 2007-13 the UK paid £4.14 billion to the EU science budget. However, it received £6.75 billion in return. There is genuine fear by the science community in the UK that the combination of potentially lost funding and being frozen out of collaborations will mean a huge impact on the world-leading science projects that European teams collaborate on.

Of course, we no longer live in global isolation, with state of the art digital technology and collaboration can still occur without crossing physical borders. In worst case scenario post-Brexit conditions scientists will still be able to communicate and share data so maybe this will be intensified in the future?

UK SMEs need long view Aspects like changing economic climate, government pledges and help and decisions made by companies supplying Britain (as well as within Britain) may dictate outcomes for SME prosperity.

Professor Roper researches SME growth and innovation and is Director of the Enterprise Research Centre. His overview indicates there may be potential in the future for gains but only if and when things have settled down. The short term looks difficult and there will be a redefined trading landscape. He said: “Small businesses need to prepare for a period of volatility as markets react. Gains in terms of reduced regulation and EU membership costs may follow, but are probably some years off.

“Over the next few weeks a weakening of sterling will help exporters, but will make euro imports more expensive, raising all small firms’ input costs. Interest rates too may need to rise, raising business borrowing costs. Longer term, European firms may also switch orders away from the UK to insulate themselves from any changes in trading relations between Britain and the EU. “The gains for small firms from Brexit are probably two to five years away. There is potential for reduced regulation and new trade deals, but the timing and effects of both remain uncertain.

Outside the EU the UK will also be free of EU competition and state aid rules allowing the UK government to provide more direct support to SMEs.”

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Big businesses awaiting new conditions

More Referendums?

Professor Christian Stadler is the author of Enduring Success, which involved researching Europe’s biggest companies. Professor Stadler said: “It is not clear what’s happening next and businesses will be reluctant to invest. I don’t expect that there will be a massive exodus, but rather than expanding in the UK, companies are likely to do it in Europe instead, particularly for businesses which export to the EU. “The devaluation of the pound should help exports slightly, but it will be an issue for all those who have EU suppliers. There is an expected contraction of the UK market, which will hit sales in the UK. “In the long term if the UK follows the Swiss model, which is essentially adopting EU regulation minus having a say in the decisions, this would be the better option for businesses as it puts dealing with the EU more or less back to where it is at the moment. This will be an issue for some industries, like banking, as they won’t have much of an influence on regulation anymore.

We see that in Switzerland for the pharma sector for example.

Politically this would be a difficult one to pull off as people have to put up with the things they did not want - most prominently immigration.

“If the UK takes a tougher stance on immigration, for businesses this will be a disaster as the EU will retaliate. Access to the EU will become difficult. For some companies this means doing business in Europe won’t be attractive any more. Others will have to deal with complicated bureaucracy. In short: a nightmare.”

As surprised as some may be at Brexit it is a move that could be repeated as other member states watch on with the vision that they can be independent from any EU controls, directives and regulations. Far right groups are seeing popularity across Europe and engaging the public on media platforms - their core message that immigration needs controls. There is potential for EU referendums to be called in France, Netherlands, Poland and Hungary. There have even been suggestions in quarters that a second referendum could be called in the UK after the observation of the initial negative effects of the vote results around Britain, although this would be unprecedented. The word ‘contagion’ has been used in Brussels in conjunction with Brexit ideology.

Could the reality of the UK choosing to break away inspire other countries to copy, could it rip apart the EU permanently? This is what the EU wants to avoid.

Three paths possible for the UK The Financial Times set out three possible paths that could occur post Brexit which it labelled: Booming Britain, a Troubled Transition and a Disastrous Decision.

The Booming Britain scenario envisages less regulatory burden as a driver. As half of Britain’s trade is with the EU, trade

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agreements with 60 countries outside the EU are governed by agreements with the bloc. If the UK can organise quickly, setting up its own agreements then this could lead to prosperity.

The Troubled Transition hinges on uncertainty which is currently what we are seeing. It means low investment in a period of observation and trying to understand what is going to happen next.

The worst case scenario is Disastrous Decision, where the UK economy gets battered, negotiations with the EU and the rest of the world are difficult and worse than before. This could lead to recession in the UK. The US for instance has said it will favour the EU over the UK in trade deals post Brexit. The size of the EU market outweighs the UK which puts the UK at a disadvantage.

reduction in population in the EU and the EU economy should be about 17% smaller but Germany and France’s share of GDP will rise by a few percent. The UK contributes around 18.7 billion Euros to the EU budget which will have an impact. The EU will need to go through a re-birth, it could be a better mechanism ultimately with more direction or it could fragment. No one knows what will happen in the next five years, let alone the next year and that is the truth. This is history in the making on a large scale and whilst change is inevitable now, whether that is a positive thing or not for both the UK and for Europe, is anyone’s guess. Let us hope we can work it all out calmly and in all of our best interests in the coming years.

Europe’s new shape With the UK leaving, the EU will still be 27 member states strong and will likely remain the world’s go-to trading body. There is a chance of some members leaving and others joining but as a powerful trading bloc the EU will likely endure. There are however, significant impacts. Without the UK there will be 13%

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The CIRQYS project is investigating the way light interacts with exotic matter and experimenting with new methodologies that could help achieve the world-changing goal of quantum based technology. Dr Takis Kontos and his team in Paris, are conducting numerous experiments in order to pioneer hybrid circuits which will illuminate the science needed to drive quantum devices

CIRQYS: Lighting the path toward quantum technology The CIRQYS project intends to provide key research in the steps toward building quantum computers. Their research is primarily about creating a new method of investigating the workings of tailored nano-systems. The team, based at Ecole Normale Supérieure and under the steer of Dr. Takis Kontos, is creating and studying artificial atoms, molecules or wires.

“Working with nanowires, carbon nanotubes in our case, is definitely challenging since those are almost microscopic objects about 10-100 micron long with a diameter of about 1 nm,” explained Dr. Takis Kontos. “We have to make devices out of these conductors. This requires nanolithography techniques. The different lithography steps are combined with evaporation of metals in ultra-high vacuum. The samples are then mounted on a microwave sample holder in a dilution refrigerator which allows to reach 20 mK. Such a low temperature is crucial for observing quantum effects in our circuits.

We then perform electrical measurements both at low frequency and very high frequency – in the GHz range.”

Light interactions with nanotubes Carbon nanotubes can be used for transistors which are building blocks for electronic circuitry. They are molecular conductors and can be used to research quantum transport.

In these miniscule environments, nanotubes are connected to normal ferromagnetic or superconducting electrodes embedded in high finesse onchip superconducting photonic cavities.

The project hinges on the niche field of cavity quantum electrodynamics. This is where scientists study the interaction between the light trapped in a reflective cavity and atoms or particles.

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At the heart of the project’s proposal is a new scheme for detecting and manipulating exotic states created via combinations of conductors with different dimensionalities and (or) electronic circuits.

“Hybrid quantum circuits are electrical circuits which combine different physical systems,” said Dr. Kontos. “Originally, we were combining different electronic systems e.g. superconductors with carbon nanotubes, ferromagnets with carbon nanotubes. We have recently taken a step further in the kind of hybrid system which we study, since we now couple these electronic systems to photons. These photons are trapped in a cavity which allows to control their coupling to the electrons of the circuits. The whole devices remain circuits since our photons lie in the microwave range. We therefore study hybrid quantum circuits made out of electrons and photons.”

This kind of circuitry could affect the future of digital technology profoundly, the advantage being that in principle, it could perform a very large number of operations in parallel.

Three important experiments The research team set out to conduct three different experiments.

The first proposed experiment was to demonstrate the strong coupling between a single spin and cavity photons, bringing spin quantum bits (qubits) a step closer to scalability. Multi-qubit testing is the goal if larger scale quantum devices are to be built.

“Very early on, in 1999, people thought to combine spins and photons of a cavity in order to use all the methods of cavity quantum electrodynamics, in order to readout, manipulate and couple distant spins. We have in fact already achieved that part of the project. The results were published in Science last summer.”

Another experiment probes coherence in Cooper pair splitters using lasing and sub-radiance.

Dr. Kontos explains further: “The second part deals with the probe of superconducting correlations in quantum dot circuits. The idea is to connect a carbon nanotube to a superconductor to implement a beam splitter – like in optics – but not for

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electrons, for Cooper pairs instead. Cooper pairs are the elementary parts of superconductors and are made out of two electrons in a spin singlet state. The singlet state is an entangled state and therefore it is very interesting to see how it can survive in a condensed matter environment.”

The final experiment is an attempt to detect Majorana modes with a cavity quantum electrodynamics architecture.

These elusive quasiparticles are the subject of intense research activity worldwide as they could be used for topological quantum computation.

“They have the intriguing property to be their own antiparticle,” said Dr. Kontos.

“However, most of the experiments carried out so far are essentially transport experiments which spoil that property in order to make an efficient detection. Furthermore, there is a consensus that one will have to do much more than what has already been measured so far, in order to prove the existence of these quasiparticles. We hope to provide an important step towards that ambitious goal.”

The project results will act as a bridge of knowledge within a realm of research that is on-going around Europe.

Collaboration with colleagues throughout Europe in locations like Madrid, Basel, Copenhagen, Regensburg, Lund, as well as within the physics department of Ecole Normale Supérieure is all part of the process.

What happens next?

“There are at least two very exciting lines of research which could be pursued after the project. The first is that finding ways to detect and manipulate exotic states enables us to couple several such exotic states. Our exotic matter-light interface would be particularly appealing since our photons are in the microwave range and therefore would allow us to coupling over macroscopic distances.

Another very interesting direction would be to use these circuits for some kind of quantum simulation of condensed matter problems.”

The potential of quantum technology to perform at rates far outstripping current computer technology makes for exciting future prospects. With this horizon in clear view, the efforts of the research team working on the CIRQYS project will provide essential stepping stones toward the reality of a golden age of quantum machines.

Carbon nanotubes can be used for transistors which are building blocks for electronic circuitry. They are molecular conductors and can be used to research quantum transport. In these miniscule environments, nanotubes are connected to normal ferromagnetic or superconducting electrodes embedded in high finesse on-chip

At a glance Full Project Title Circuit QED with hybrid electronic states (CirQys) Project Objectives The project CirQys aims to develop a new scheme for detecting and manipulating exotic states formed by combinations of conductors with different dimensionalities and/or electronic orders, using tools of cavity quantum electrodynamics to study in a very controlled way the interaction of light and exotic matter. The experimental technique proposed in the project will inaugurate a novel method for investigating the spectroscopy and the dynamics of tailored nano-systems.

Contact Details Project Coordinator, Dr Takis Kontos Laboratoire Pierre Aigrain Ecole Normale Supérieure 24, rue Lhomond 75231 Paris Cedex 05 France T: +0033 1 44 32 25 18 E: kontos@lpa.ens.fr W: http://www.lpa.ens.fr/spip. php?rubrique117 Cavity Photons as a Probe for Charge Relaxation Resistance and Photon Emission in a Quantum Dot Coupled to Normal and Superconducting Continua » L.E. Bruhat, J.J. Viennot, M.C. Dartiailh, M.M. Desjardins, T. Kontos and A. Cottet, Phys. Rev. X, 6, 021014 (2016).

Coherent coupling of a single spin to microwave cavity photons » J.J. Viennot, M.C. Dartiailh, A. Cottet and T. Kontos, Science, 349, 408 (2015).

Dr Takis Kontos

superconducting photonic cavities

After electrical engineering studies at Supelec, Takis Kontos did a PhD thesis on the interplay between superconductivity and ferromagnetism at the CSNSM, Orsay, with Marco Aprili and Jérôme Lesueur. He did after a posdoc at the university of Basel, Switzerland, in the group of Prof. Christian Schönenberger where he worked on spin injection in carbon nanotubes. He has been CNRS researcher at the Laboratoire Pierre Aigrain, at the physics department of Ecole Normale Supérieure since 2005. He has recently started an activity on mesoscopic quantum electrodynamics in close collaboration with Audrey Cottet.

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Dirac materials are the subject of great interest among researchers, with scientists seeking to make full use of their low-energy electronics properties. We spoke to Professor Alexander Balatsky about his work in investigating the properties of Dirac materials and searching for ways to modify their functionality, work which could widen their range of potential applications

A peek into the future of material design A sub-class of

conducting materials characterised by the presence of nodes in the momentum space, the low energy electronic properties of Dirac materials hold important implications for the future of material design. Based at the Nordic Institute for Theoretical Physics in Stockholm, Professor Alexander Balatsky is the Principal Investigator of a research project which aims to harness the properties of these materials. “The idea behind the project is to take the functionalities of Dirac materials and investigate what intelligent suggestions we can make to take advantage of these properties,” he outlines. Examples of Dirac materials include D-wave superconductors, graphene and topological insulators, which all share certain common features. “With Dirac

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materials, we see excitations of particles that are concentrated in small regions on the phase space. The crucial difference between Dirac materials and conventional metals is that typically fewer of these low-energy excitations are found in Dirac materials compared to conventional metals like copper,” explains Professor Balatsky.

Material functionality These features play a large role in determining the functionality of a material and its suitability for common applications. The project is looking at the functionality of Dirac materials in a fairly broad sense, where the properties of the material can be dramatically changed by relatively small modifications. “The presence of low-lying excitations enables

the functionality of a material. The excitations of quasi-particles leave the material as a low-energy vapour around the Fermi surface,” says Professor Balatsky. The Fermi surface can be thought of as a boundary within a material, which delineates occupied and unoccupied states; Professor Balatsky says Dirac materials have some distinguishing characteristics in this respect. “Instead of a Fermi surface, we see that there is a drastically reduced low energy phase space, or gap, available to produce lowenergy excitations,” he explains. “The active regions where we see electron and hole excitations are called Dirac nodes as they are showing up as lines and points.”

Researchers are investigating the fundamental principles behind the emergence of these Dirac nodes, work

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which could hold important implications in terms of material functionality. The Dirac equation, which describes the linear dispersion (energy/momentum) relation of electrons at relativistic speeds, is an important element of this work, providing a framework to predict the behaviour of particles within a material. “The Dirac equation describes the behaviour of fermions, and can also be used to describe the behaviour of bosons,” outlines Professor Balatsky.

This is central to understanding the emergence of Dirac nodes. The presence of Dirac nodes in Dirac materials is typically controlled by forms of symmetry of the lattice; Professor Balatsky says the nature of the symmetry depends on the material.

“If you look at topological insulators, the presence of the Dirac nodes is related to the spin-orbit coupling that connects the motion of electrons with the spin and the time-reversal symmetry of the material.

In the case of graphene, it’s an inversion symmetry,” he explains. These symmetries are highly complex in the cases of some materials, yet once the symmetry is established, Professor Balatsky says it is possible to look towards describing the material as a Dirac material. “Once you have identified the nodes, you can make some universal statements about the behaviour of electrons, or excitations, in those nodes,” he says.

This work in investigating the emergence of Dirac nodes is an essential step towards modifying the properties of

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these low-energy excitations in the nodes. This would offer exciting potential, enabling researchers to open energy gaps and control the electronic state of materials. “Once the nodes are present we can look at the ways of modifying their properties and hence changing the properties of the material like make it insulating instead of being conductive. We would be able to drastically change the response of materials at low energies. And we would be able to achieve this by modifying only

at specific points within the overall structure. “We can essentially place the atoms, quantum dots, or certain particles, in certain positions in the lattice. That’s very exciting,” says Professor Balatsky.

Researchers plan to use the sensitivity of nodes in the electron spectrum of Dirac materials to induce controlled modifications of the Dirac nodes. “We’re very interested in exploring the behaviour of these Dirac materials when we see certain responses,” says Professor Balatsky.

The idea behind the project is to predict properties of Dirac materials and investigate what intelligent suggestions we can make to take advantage of these properties a very few points on the surface,” explains Professor Balatsky. The gap in Dirac materials can be tuned, enabling researchers to modify their functionality.

“For instance, we can make a material that reflects specific frequencies of light,” he outlines.

Artificial Dirac Materials The development of new technologies over the last twenty years has greatly improved researchers’ ability to manipulate metals at atomic scales, opening up new possibilities in terms of tuning and modifying material functionality.

Researchers are now finding that it is possible to build artificial materials where Dirac nodes can be introduced on-demand,

This work could both significantly enhance researchers’ theoretical understanding of Dirac materials, and also have a significant practical impact on material design. With a deeper theoretical knowledge of Dirac materials, materials could be designed to tune the energy profiles of Dirac carriers, helping to improve energy efficiency. “This research will contribute to an improved understanding of thermo-electrics, essentially looking at how we can control heating elements and make them more efficient. We are investigating how we can control conductivity,” continues Professor Balatsky.

This research is central to the potential future applications of Dirac materials.

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At a glance Full Project Title DM Dirac Materials Project Objectives The discoveries of superfluid phases in Helium 3, high Tc superconductors, graphene and topological insulators have brought into focus a class of materials where quasiparticles are described by the Dirac equation, the same equation governing the behavior of relativistic particles. Materials in this class, Dirac materials[1], exhibit unusual universal features such as: Klein tunneling, chiral symmetries, and impurity resonances. The objective of this project is to explore the properties shared by these materials and discuss the unique role of symmetries that protect the Dirac spectrum. Our results will expand our theoretical understanding and guide the design of materials and engineered geometries that allow tunable energy profiles of Dirac carriers and realization of states, like Dirac bosons[2], which cannot be found in nature.

Project Partners Center for Quantum Materials, Stockholm University and KTH. Contact Details Professor Alexander V. Balatsky, NORDITA Roslagstullsbacken 23, 10691 STOCKHOLM T: + 46 8 553 780 43 E: balatsky@kth.se W: http://diracmaterials.org/

While a number of applications of graphene have been identified for example, in fields as diverse as energy, biomedicine, and composites and coatings, the applicability of a material depends heavily on its functionality, reinforcing the wider importance of Professor Balatsky’s research. “We’re continuing to look at interesting expressions of these Dirac equation structures and Dirac nodes,” he says. Many of the general features of Dirac materials have also been observed in other areas of materials science. “Dirac materials are a sub-class of metals – graphene is a prominent example, but there are also others. There are also unconventional superconductors, such as high temperature super conductors. As research has progressed, we’ve seen the same descriptions, the same phenomena, emerging from different parts of materials science research,” says Professor Balatsky.

Research will continue into both the potential applications of Dirac materials,

and fundamental questions around their applications for energy efficient electronics applications.

“We’re investigating the non-equilibrium state of Dirac excitations. We describe transient and time dependent novel states that one can generate in the Dirac nodes by applying pulses of light, magnetic and electric fields to Dirac materials. A natural analogy would be if you stretch a spring out of equilibrium for a while it can take certain shapes.

But these very interesting states are not available in equilibrium. We are looking for the novel states of Dirac materials that are not available in the equilibrium,” says Professor Balatsky. There is also significant scope for further research into the functionalisation of Dirac materials. With the development of new imaging and manipulation techniques there is significant potential to capture exciting new phenomena in quantum materials, opening up new avenues of research and potential applications.

Condensed Matter group at Nordita: Front row: (left to right) S. Pershoguba, S. Borysov, C. Triola; Second row: (left to right) A.Balatsky, Y. Kedem, M. Geilhufe, A. Pertsova.

[1] T.O. Wehling, A.M. Black-Schaffer & A.V. Balatsky (2014) Dirac materials, Advances in Physics, 63:1, 1-76 [2] S. Banerjee, J. Fransson, A. M. Black-Schaffer, Hans Ågren, and A. V. Balatsky, Granular superconductor in a honeycomb lattice as a realization of bosonic Dirac material [1] Phys. Rev. B 93, 134502 (2016)

Professor Alexander V. Balatsky

Alexander V. Balatsky obtained his doctoral degree from the Landau Institute for Theoretical Physics. After postdoctoral training and a research assistant professor position at the University of Illinois at Urbana Champaign, he went to Los Alamos National Laboratory as an Oppenheimer Fellow where, in 2014, he became director of the new Institute for Functional Materials. Over the past several years he has been elected as a Fellow of various prestigious organizations: Fellow of the American Physical Society in 2003, Los Alamos Fellow in 2005, and the American Association for the Advancement of Science Fellow in 2011.

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Plasma treatment for the surface of porous materials The suitability of a material to certain applications is determined to a large degree by its surface properties. Professor Rino Morent tells us about the PLASMAPOR project’s work in using non-thermal atmospheric pressure plasmas to modify the properties of porous materials, research which promises to have a significant impact on science and society A great deal

of research attention has been centred on porous materials in recent years, with scientists seeking to modify their surfaces to achieve characteristics relevant for specific applications. However, modifying the entirety of a porous material in a homogenous way is a technically challenging task, given the narrow dimensions of the network of pores within such materials. “When you are dealing with a porous material, you also have to alter the internal surfaces, the surfaces within the pores,” explains Professor Rino Morent. Based at Ghent University in Belgium, Professor Morent is the Principal Investigator of the PLASMAPOR project, an ERC-backed initiative investigating innovative methods of modifying porous materials.

“We are studying porous materials, and we are looking at treating them with plasma,” he explains.

There are a wide range of potential applications of porous materials, from mechanics and engineering through to biophysics, materials science and hydrogeological applications. While fully aware of this wider potential, researchers in the PLASMAPOR project are focused on two main applications. “We are looking at the use of porous materials as filter materials, and the other application is as scaffolds used in tissue engineering,” says Professor Morent. Researchers have been working to tailor the production of porous materials to meet the specific needs of various different potential applications,

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yet it has proved difficult to modify the central part of these materials with existing production techniques. Tailoring the central part of the porous material after it has been produced could significantly widen the range of applications.

Novel approach The use of plasma represents a novel approach to this challenge. As partially

ionised gases containing electrons, ions, radicals and photons, as well as neutral atoms or molecules, plasmas have not historically been used to modify the surfaces of porous materials. “Up to this point there hasn’t been a lot of research into treating porous materials with plasmas, largely because it’s difficult to get the plasma to enter the pores,” explains Professor Morent. Previously, plasma introduced into a porous material would

Fluorescent micrographs after live/dead staining of ATMSC cells cultured on acrylic acid plasma coated PCL scaffolds after 2 days of cell seeding. (scale bar: 500 μm). This clearly shows the ingrowth of cells into the porous structure.

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burn above the key structures, without entering the narrow channels, while the density of the active species of the plasma is also a significant technical hurdle.

“Especially at atmospheric pressure, the density of the active species is quite high, and they interact with each other rather than diffusing into the pores of a porous material,” continues Professor Morent.

By modifying the operating parameters, Professor Morent and his colleagues have been able to get plasma to enter the pores, opening up a new angle on research. The project is working with non-thermal plasmas, which are differentiated from thermal plasmas on the basis of the relative temperatures of the electrons, ions and neutrals, and which are being used to modify the surface of materials on the micro-metre scale. “If you perform what I would call a normal treatment, you see that only the upper layers of the porous material are treated, and not the inside of the pores.

We’re working with non-thermal plasmas, in which it is only the electrons that have high energies. So the plasma itself remains cold - that’s why we call them non-thermal, cold plasmas. These are very interesting plasmas, as they can be used for heat-sensitive materials,” explains Professor Morent.

Researchers plan to introduce specific functional groups into the pores with these plasmas, by which the surface of the material can be modified. This research is central to understanding how the properties of porous materials can be controlled. “We want to introduce certain functional groups, containing oxygen or nitrogen, into the pores, and this will change specific properties of the material,”

biomedical implants and tissue engineering, an area of great interest to researchers in the PLASMAPOR project.

The newly developed plasma reactor concepts will be used to modify the internal surface of porous biodegradeable polymer scaffolds, which permit both the migration of cells involved in tissue repair and the ingrowth of blood vessels, depending on their pore size and

We want to introduce certain functional groups, containing oxygen or nitrogen, into the pores, and this will

change specific properties of the material

outlines Professor Morent. The addition of specific functional groups can influence how cells grow on the surface of the material for example, which Professor Morent and his colleagues are investigating. “First we develop the material, we try to chemically and physically determine what happens, and then we are working with researchers who are looking at the behaviour of the cells,” he says.

Biomedical application This holds clear relevance to the potential use of these porous materials in

geometry. “With a scaffold, the idea is to produce it in a biodegradeable polymer, and after a period of time it will degrade.

The hope is that in that time, new cells and tissue will grow and establish their own, self-supporting structure,” explains Professor Morent.

This would represent a significant improvement on previous methods.

Using a material that only offers mechanical support – without guiding tissue recovery – leads in most cases to inadequate integration of the implant into the surrounding tissue, whereas a biodegradeable polymer scaffold would

Atmospheric pressure plasma penetrating in medical polymeric tubes. (no tube – 2 mm tube – 1.02 mm tube – 0.86 mm tube)

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At a glance ideally support the growth of tissue.

While the project’s research is largely fundamental in nature, a number of material samples have been developed, which Professor Morent and his colleagues are looking to test and evaluate. “We want to try to test these samples in real environments,” he says.

“First of all we treat these samples and then we test them and see what happens, both physically and chemically.”

Further testing of these samples will form an important part of Professor Morent’s future agenda, along with continued research into the penetration of chemically active species into porous structures. This will underpin efforts to

Full Project Title Plasma penetration into porous materials for biomedical, textile and filtration applications. (PLASMAPOR)

Life/dead brightfield image of a acrylic acid plasma coated PCL scaffold with ATDC5 cells aiming for cartilage regeneration.

With a scaffold, the idea is to produce it in a biodegradeable polymer, and after a period of time it will degrade. The hope is that in that time, new cells and tissue will grow and establish their own,

self-supporting structure achieve the long-term goal of enabling highly controlled penetration of the plasmas into porous materials. “We have achieved quite a good level of penetration of the functional groups that we see into those porous structures. In terms of the cells, we have already had positive results that demonstrate our treatment of the material surface is quite effective,” outlines Professor Morent.

This research field is still in its relative infancy, and further research is required before the internal surface of 3D structures can be specifically and selectively altered using plasmas.

However, with concern intensifying over the environmental impact of traditional methods of surface treatment, Professor Morent believes that a plasma-based modification process offers an attractive alternative to current approaches. The PLASMAPOR project aims to make an important contribution to the development of plasma technology; the breadth of their research will open up new perspectives on what can be achieved with atmospheric pressure plasma technology, and how it can be used to precisely modify the properties of porous structures.

Plasma

(a)

(b)

Schematic representation of (a) macroplasma burning above a porous structure and (b) microplasmas burning in the pores of a porous structure.

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Project Objectives This project explores the nearly undeveloped field of penetration of non-thermal plasma into porous structures. New plasma reactor concepts are developed enabling effective plasma penetration. These newly developed plasma reactors are employed for the internal surface modification of porous biodegradable polyester scaffolds used in tissue engineering. Besides the development of biomedical implants, the possibilities for the design of functional porous textiles and advanced filter materials is also explored.

Project Funding 1.518.800 euros, ERC Starting Grant, call 2011, project number 279022.

Contact Details Department of Applied Physics Faculty of Engineering and Architecture Ghent University (UGent) Sint-Pietersnieuwstraat 41, B-9000 Ghent, Belgium T: +32 (0)9 264 42 57 E: Rino.Morent@UGent.be W: http://www.ugent.be/nl/onderzoek/ ugent/trackrecord/eu-portfolio/morent.htm Iu. Onyshchenko, N. De Geyter, A. Yu. Nikiforov, R. Morent /Atmospheric pressure plasma penetration inside flexible polymeric tubes/ Plasma Processes and Polymers, 12(3): pp. 271-284, 2015

Rino Morent

Rino Morent obtained a degree in physics at Ghent University (Belgium) in 2000.

He received in 2004 the Ph.D. degree in physical engineering on VOC abatement with atmospheric pressure DC discharges.

Since 2012, he is associate professor at the Research Unit Plasma Technology of the Department of Applied Physics at the Faculty of Engineering and Architecture at Ghent University. In 2012 he obtained an ERC Starting Grant PLASMAPOR entitled “Plasma penetration into porous materials for biomedical, textile and filtration applications”.

He is author or co-author of more than 90 papers in international peer-reviewed journals and 15 book chapters and is member of the editorial board of Applied Surface Science and Plasma Chemistry and Plasma Processing. His current research interests are focused on cold atmospheric pressure plasmas for materials and environmental applications.

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Plasma modification holds the key to surface properties Electrospun nanofibrous mats are an exciting class of materials, now researchers in the PLASMATS project are investigating the use of atmospheric non-thermal plasma technology in their development and functionalization. This research holds wider relevance to tissue engineering, and could also open up further avenues of scientific investigation, as Professor Nathalie De Geyter explains A type of material produced using the electrospinning method, electrospun nanofibrous mats hold rich potential across a number of applications.

However, the ultimate suitability of these materials for specific applications like tissue engineering depends to a large degree on their surface properties, an area of great interest to Professor Nathalie De Geyter, the Principal Investigator of the PLASMATS project.

“The main idea behind the project is to create what we call biodegradable scaffolds which can be used in tissue engineering applications,” she says.

Electrospun mats have similar dimensions and mechanical properties to human tissue, underlining their potential in tissue engineering applications. “If

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you want to implant a material into the body, it should have more or less the same mechanical properties as human tissue,” continues Professor De Geyter.

“As human tissue partly consists of nanofibrous materials, it would be great if we could implant a material that consists of these nanofibres, since they closely mimic the extra-cellular matrix of human tissue.”

There are some major technical challenges to address first however. A key problem is that these electrospun materials do not ‘like’ cells, as most of the biodegradable polymers used in their development have high hydrophobicity, leading researchers to focus a great deal of attention on modifying surface properties. “If we

want to incorporate electrospun materials on the human body, or inside the human body, we need to significantly improve the cellular interactions,” explains Professor De Geyter. A number of chemical techniques are available to improve cellular interactions, but they also adversely affect the biocompatibility of the material, so researchers are instead using non-thermal plasma to modify the surface; Professor De Geyter says there are some clear benefits to this approach. “It does not require the use of water or chemicals, and it’s a completely dry process. So you do not have the risk of leaving some solvents on the scaffolds, which is very beneficial for the biocompatibility of the scaffolds,” she outlines.

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Electrospinning process

t he voltage you apply between the

The project is also working to develop improved electrospun materials, making use of non-thermal plasma technology both before and after the electrospinning process. The electrospinning process itself is a reliable method of producing fibrous polymer mats. “In the electrospinning process, we start from a polymer solution which is introduced into a capillary. The polymer solution is then subjected to an electrical field so that the induced

capillary and the collector plate for example, and change the distance between them,” says Professor De Geyter.

Researchers can then assess the influence of these operational parameters on the final properties of the nanofibres, or in fact whether they are produced at all. While a polymer solution is an essential component of the electrospinning process, it’s not always possible to produce nanofibres from all

incorporate electrospun materials on the human body, or inside the human body, we need to significantly improve the cellular interactions If we want to

repulsive electrical forces on the liquid surface overcome the surface tension forces. Eventually, a charged polymer solution jet is ejected from the capillary and starts to follow an unstable whipping path in the region between the capillary and a collector, during which solvent evaporation occurs, leaving random polymer nanofibers on the collector,” explains Professor De Geyter. Researchers are investigating the impact of changing different operational parameters in this process on the nanofibres. “We perform the electrospinning process and examine different parameters. So you can change

polymer solutions. “You need a polymer solution with specific properties, such as conductivity and viscosity, to create these nanofibres. With some polymers, we find that instead of producing nanofibres, small beads are produced,” continues Professor De Geyter. This points to another aspect of the project’s work, with Professor De Geyter and her colleagues using non-thermal plasma technology to modify the properties of these polymer solutions. “How is the polymer affected by the plasma? How are the solvent molecules affected by the plasma? We are looking at the different

effects that the plasma has on the polymer solution,” she outlines.

There is also a work package within the project dedicated to studying the interactions between a non-thermal plasma jet and electrospun mats. An atmospheric pressure plasma jet can be used to incorporate specific functional groups on the surface of the material; it is essential to first investigate the interactions between the plasma jet and the electrospun mat. “We look at the key parameters of the plasma, such as current, voltage and active plasma species. We then use the plasma to modify the surface of the nanofibres, and investigate the surface properties of the material itself,” explains Professor De Geyter. From these investigations, researchers can then look to correlate the plasma operating parameters with the active species in the plasma phase and the functional groups created on the surface, gaining fundamental insights into plasma-surface interactions. “We use optical emission spectroscopy to examine the active species in the plasma, and we are trying to correlate this with the final chemical composition of the surface,” says Professor De Geyter.

Biomedical applications The wider goal in this research is to develop electrospun mats with properties suitable for biomedical engineering, more

Figure 1. Scanning electron microscopy image of electrospun poly-ε-caprolactone (PCL) fibres (average diameter of the fibres: 107 ± 26 nm)

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At a glance

Fig 2 (a)

Fig 2 (b)

Fig 3 (a)

Fig 3 (b)

Full Project Title Plasma-assisted development and functionalization of electrospun mats for tissue engineering purposes (PLASMATS) Project Objectives Within this ERC project, two fascinating research themes, electrospinning and plasma technology are combined. Electrospun nanofibrous matrices are unique materials with tremendous possible applications. Nevertheless, the development and functionalization of these materials remain very challenging tasks. In this project, non-thermal plasma technology is utilized to create advanced biodegradable electrospun mats with unprecedented functionality and performance, which can result in a major breakthrough in the field of tissue engineering.

Project Funding ERC Starting Grant, call 2013, project number 335929: Start date: 1-2-2014 / End date: 31-1-2019.

Contact Details Project Coordinator, Professor Nathalie De Geyter Department of Applied Physics Faculty of Engineering and Architecture Ghent University (UGent) Sint-Pietersnieuwstraat 41, B-9000 Ghent, Belgium T: +32-(0)9-264 38 37 E: Nathalie.DeGeyter@UGent.be W: http://www.ugent.be/nl/onderzoek/ ugent/trackrecord/eu-portfolio/degeyter

Professor Nathalie De Geyter

Professor Nathalie De Geyter obtained a materials engineering degree at Ghent University (Belgium) in 2004, and received a PhD in physical engineering on cold plasma treatment of polymers in 2008. Since 2014, she has been associate professor at the Research Unit Plasma Technology of the Department of Applied Physics at the Faculty of Engineering and Architecture at Ghent University. In 2014, she also obtained an ERC Starting Grant PLASMATS entitled “Plasmaassisted development and functionalization of electrospun mats for tissue engineering purposes”. Her current research interests are focused on plasma surface modification of materials used for (bio)medical applications and plasma medicine.

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Figure 2. (two upper images) Scanning electron microscopy images of human foreskin fibroblasts on untreated (a) and nitrogen plasma-treated (b) PCL nanofibers 1 day after cell seeding.

This figure clearly shows the positive effect of nitrogen plasma treatment on fibroblast adhesion and proliferation on electrospun PCL mats.

Figure 3. (two lower images) SEM images of PCL nanofibers starting from an untreated (A) and plasma-treated (B) PCL polymer solution in a mixture of chloroform and N,N-dimethylformamide.

Plasma treatment can thus greatly improve the electrospinnability of PCL leading to the formation of uniform nanofibers without the presence of beads. specifically soft tissue applications.

Researchers are now looking to test the effectiveness of the nanofibrous mats for tissue engineering purposes, in collaboration with colleagues at Ghent University. “We place cells on the surface of the materials, after the plasma modification step, and then check how the cells behave,” says Professor De Geyter. The morphology of the cells on the surface is an important indicator of the material’s suitability for tissue engineering. “If the cells remain round, then that means that the material really does not like the cells. If the cells start to become elongated, and they start to multiply, then we can see that the cells want to grow on the scaffolds,” explains Professor De Geyter. “We can also do some quantitative measurements using either an MTT assay or an MTS assay, enabling us to determine the amount of viable cells on a material.”

Researchers aim to generate nanofibres with the required cellular interactions in vitro, after which the next step will be to

start in vivo experiments, first on animals and then on humans. This represents an important step towards the practical application of these biodegradable scaffolds. “If we are able to generate scaffolds with the desired mechanical properties, and with good surface properties in terms of biocompatibility and cellular interactions, then we are a step closer to implementation,” outlines Professor De Geyter. Beyond the potential societal impact of their research, Professor De Geyter says the project’s work also has important scientific implications. “We expect that our research into treating polymer solutions will have a major impact, because this is not a very wellexplored area.

The fundamental knowledge that we are gaining on how plasma can be used to chemically and physically modify polymer solutions is really novel. This could lead to a number of other studies and maybe other applications of plasma for liquid treatment,” she says.

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FIG. 1. Frustrated magnetism is one major direction within the TOPOLECTRICS project. Shown is a phase diagram analysis for the J1-J2-Jd Heisenberg model on the kagome lattice. In comparison to the upper left classical phase diagram exhibiting different magnetic orders (magnetic ordering peaks such as for cuboc or ferromagnetic order are sketched in grey), a new paramagnetic regime (denoted in red) appears in the quantum phase diagram. The upper right figure displays how pressure modifies the effective Heisenberg parameters for different compounds. Further details can be found in Iqbal et al., Phys. Rev. B 92, 220404(R) (2015).

New insights into topological quantum states Topological quantum states of matter have become a major branch of both theoretical and experimental research, which now demands a new theoretical language. Professor Ronny Thomale, the Principal Investigator of the Topolectrics project, tells us about their work in developing a theoretical framework to unify the appearance of topological quantum states of matter Many advances in

physics have been achieved through scientific experimentation, where researchers observed new and exotic phenomena which they then studied and analysed, gaining new insights. However, theoretical development has also been a central part of the story of scientific development, says Professor Ronny Thomale, the Principal Investigator of the Topolectrics project, an EU-backed initiative investigating the topological quantum states of matter which result from electronic interactions.

“We want to develop a theoretical framework, a theoretical language, in which we can unify the different appearances of topological quantum states of matter,” he says.

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Topological quantum states of matter There are many topological quantum states of matter in nature. Now researchers in the Topolectrics project are trying to help experimentalists identify them, using their topological properties. The discovery of the Integer Quantum Hall Effect by German scientist Klaus von Klitzing, work for which he was awarded the Nobel Prize for Physics in 1985, is a central part of the story. “The Integer Quantum Hall Effect is a phenomenon observed in gallium arsenide heterostructures, where electrons are placed in what is effectively a 2-dimensional environment and subjected to a strong magnetic field,”

outlines Professor Thomale. “Klaus von Klitzing found that he could perform a conductivity measurement where the low energy transport behaviour is fully characterized by chiral modes at the boundary of the sample. With some predecessors such as polyacethylene and superfluid Helium-3 not to be forgotten, this truly gave birth to the field of topological quantum states of matter.”

This conductivity measurement was found to depend only on topological aspects of the system, implying it to be invariant under local perturbations, such as changing the shape of the sample’s boundary. This is an important insight, which has played a fundamental role in subsequent research. “Von Klitzing’s

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conductivity measurement of the Integer Quantum Hall Effect would basically be an integer multiplied by a ratio between natural constants of the universe forming the quantum of conductance, which is e2 /h, where ‘e’ is the electronic charge and ‘h’ is the planck scale,” explains Professor Thomale. “This experiment allowed physicists to derive a ratio between the electronic charge and the planck scale that was very accurately measurable. There are only a few constants of the universe – there’s the velocity of light and others, but there aren’t that many, so this establishes a fundamentally important finding. This particularly applies to the Planck scale which otherwise is very difficult to measure.”

The importance of this discovery lies in its universality, making the Integer Quantum Hall Effect enormously exciting. “The transport properties of that system, which is what conductance or resistance is about, are completely and solely determined by universal properties that actually, by themselves, can be linked to topology. This universality thus has its roots in the topological character of the system, this topological quantum state of matter, as first theoretically framed by David J Thouless,” says Professor Thomale.

The use of topology in physics, in its current diverse appearance, is a relatively recent development. Topology was traditionally thought of as a branch of mathematics, until its relevance to physics research became apparent. “Physicists realised in the early ‘80s that there are quantum states of matter where the perspective from topology allows you to grasp what distinguishes such quantum states of matter from other states which

otherwise would be hard or impossible to tell apart,” explains Professor Thomale.

This is a fundamental question in research.

“How can we distinguish between different states of matter? From there, how can we make the measurements we need to draw conclusions on the nature of a given state of matter found in an experiment?” continues Professor Thomale.

Theoretical language Researchers in the Topolectrics project aim to develop a theoretical language which unifies the different appearances of these topological quantum states of matter. This language could act as a

group schemes, a type of mathematical toolkit that enables researchers to distill effective descriptions depending on the energy scale at which it operates. “A lot of the toolkits that we have developed are designed to connect a bare electronic model description at high energies with an effective electronic model description at low energies. So, relating the energy scale with the temperature, how can we connect a system that we would be able to understand at high temperatures, with what it would eventually go into as we lower the temperature? That’s the top-down aspect of our research,” continues

We aim to unify descriptions of fields that have been found to be connected, but in a relatively weak way. We want to strengthen these connections and really make the cross-links more explicit and more rigorous in a theoretical language framework for future research development. “We aim to unify descriptions of fields that have been found to be connected by topological universality, but only in a relatively weak way on the basis of microscopic properties. We want to strengthen these connections and really make the crosslinks more explicit and more rigorous in a theoretical language,” explains Professor Thomale. “By cross-linking them, we can develop a universal framework of how to think about them that paves the way for the next wave of scientific discovery.”

The project is following two different approaches to this work. The first is a top-down approach, where the project is developing tailored renormalization

Professor Thomale.

The bottom-up approach meanwhile is designed to understand a given state of matter in more detail, such as fractional quantum Hall states, spin liquids and spin chain states, by analysing and reverseengineering topological quantum states.

The goal in this work is to establish stronger links between bare electronic models and low-energy effective models.

“With the bottom-up approach we start from these microscopic models which might be representative of a larger universal class of quantum states of matter,” outlines Professor Thomale. “So you pick a certain model – maybe it’s chosen intentionally so that you can solve it more easily, or you can tackle it at a certain unique angle.”

FIG. 2. Within the TOPOLECTRICS projects, interaction effects for topological insulators are investigated. Shown are low-energy exact diagonalization spectra of a three-dimensional topological insulator protected by time-reversal symmetry.

Coating the two halves of the sphere with oppositely polarized magnetization (left) gives rise to a chiral fermion at the equator, while a single Majorana mode emerges at the boundary between a surface superconductor and a magnet (right).

Further details can be found in Neupert et al., Phys. Rev. Lett. 115, 017001 (2015).

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At a glance FIG. 3. Developing theoretical findings towards experimentally relevant prediction is a key objective of the TOPOLECTRICS project. We have predicted the material SrPtAs to exhibit a topologically non-trivial superconducting state. Shown is the Fermi surface structure, featuring Majorana-Weyl nodes of the superconducting order parameter. In the projected (010) surface Brillouin zone, Fermi arcs of chiral Majorana fermions are found. Further details can be found in Fischer et al., Phys. Rev. B 89, 020509(R); 90, 099902(E) (2014).

Superconducting materials This research may seem theoretical in nature, but Professor Thomale’s research also holds practical implications, notably in terms of energy sustainability. One major area of Professor Thomale’s research is superconductivity, a phenomenon where electrical resistance disappears at a critical temperature. “The study of topological states of matter, as we think of them now, started in the ‘80s with Klaus von Klitzing, while superconductivity was discovered by Heike Kammerlingh Onnes in 1911, so the field is over 100 years old,” he explains. “But these fields are linked, and we want to contribute to strengthening these links in our project.”

A unified theoretical language would link this field in a much more rigorous way to other disciplines in physics, giving researchers a clearer framework to investigate superconducting materials.

Such materials have the potential to revolutionise our energy supply. “When you transport electricity over large distances via standard copper cables, a lot of energy is lost. However, superconductors are capable of carrying electric energy without any friction loss,” points out Professor Thomale.

“If we used superconducting cables to connect a city with another power plant, the energy loss would be zero. So we could actually produce electricity in a much more de-localised fashion than we can today.”

The second potential technological application of the project’s research is in using these topological quantum states of matter to define quantum bits (qubits), which are the unit of information in the field of quantum computing. In contrast to the classical bit used in conventional computers, which can be one of only two values, qubits can be in a superposition that combines both. “Today’s computers are basically comprised of a series of manipulations of 0s and 1s. These qubits would replace the classical bits, and would

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allow us to define a totally new architecture of how computers can work. A huge community of scientists is currently working on various branches of this direction,” outlines Professor Thomale.

This would represent an important step in the development of quantum computers, which could potentially solve complex problems much more quickly than conventional computers. However, while Professor Thomale is interested in exploring potential commercial applications of his work, he remains particularly committed to continuing his research into fundamental questions. “The diversity and richness of condensed matter physics in this era is simply incredible,” he enthuses.

A lot of current research centres on bringing high-energy physics into tabletop condensed matter experiments. “That’s one of the big areas of reserach, in which I expect to see some of the biggest discoveries unfolding in the upcoming decades,” outlines Professor Thomale. This is an exciting time in solid state physics, with Professor Thomale saying there is enormous scope for further investigation, at a fraction of the cost incurred in other large-scale high-energy physics projects such as the LHC. Topological phases are vital to contributing to this direction. “Very often these topological quantum states of matter come along with new effective degrees of freedom, i.e. quasiparticles, that are unheard of,” he explains. This could also allow researchers to re-visit concepts as the Majorana fermion, which was put forward by the mysterious Italian physicist Ettore Majorana in 1937. “Majorana made amazing predictions, and a lot of people in high-energy physics were very excited by them, but they have not been unambiguously discovered in e.g. the double beta decay.

Now researchers are very close to achieving this in solid state physics,” continues Professor Thomale.

Full Project Title Emergence of Topological Phases from Electronic Interactions (TOPOLECTRICS) Project Objectives In the TOPOLECTRICS ERC starting grant research plan, we investigate topological quantum phases which result from electronic interactions. The key objective is to provide a rigorous link between bare electronic models and low energy effective models hosting emergent topological quantum phases.

Project Funding 1.3 million Euros Contact Details Principal Investigator, Professor Ronny Thomale Julius-Maximilians Universität Würzburg Institut für Theoretische Physik I (TP1) Am Hubland D-97074 Würzburg T: + 0931 31 86225 E: rthomale@physik.uni-wuerzburg.de W: https://erc.europa.eu/projects-andresults/erc-funded-projects/topolectrics

Professor Ronny Thomale

Ronny Thomale is a Professor of Theoretical Physics at the University of Wuerzburg.

He gained his PhD from the University of Karlsruhe in 2008, after which he worked at several universities in both Europe and America, before taking up his current position in September 2013. His main area of research is the theoretical description of strongly correlated electron states.

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Cold gas experiments could potentially act as quantum simulators, from which researchers could gain new insights into many intractable models in condensed matter physics. Professor Lode Pollet tells us about the QUSIMGAS project’s work in developing new methods to describe experiments at very low temperatures

New methods to open a window to new physics The use of ultracold atoms, maintained at temperatures of a few nanokelvin, could help researchers gain a deeper understanding of many complex models in condensed matter physics. However, while experimentalists continue to make progress in lowering the temperature and creating non-local interactions, theorists will soon face a hard wall in the way that these experiments can be described. “The problem is that there are no methods that can describe the more complicated particle interactions at lower temperatures. So we need to develop new methods,” explains Professor Lode Pollet. Based at LudwigMaximilians University in Munich, Professor Pollet is the Principal Investigator of the QUSIMGAS project, an ERC-backed initiative, which aims to develop novel quantum methods relevant to these temperature regimes. “We would like to develop new methods, so that we can still numerically, quantitatively and precisely, describe experiments when they get to these strongly-correlated regimes,” outlines Professor Pollet.

Research paradigm Of the experiments so far, Professor Pollet says the most successful have been those on bosons, in particular investigations into a dilute gas of Rubidium atoms (87Rb).

“There is a cooling process which takes this to quantum degeneracy – it involves several stages, it was developed mostly in the ‘80s and early ‘90s. Experiments have to reach Bose-Einstein condensation – that means the quantum degeneracy of the bose gas,” he explains. In the early ‘2000s researchers started creating an additional

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optical lattice for the atoms, when the physics of the atoms changes from being a dilute gas to a tight-binding model typical of condensed matter physics. The physics at this point is dominated by localisation and atomic tunneling. “There is competition between strong interactions and kinetic energy, which may or may not give rise to insulating phases and hence to strongly correlated many-body physics,” says Professor Pollet.

cannot be solved, its relevance for a material remains questionable. “With a validated cold-atom experiment, a real material can possibly be understood in terms of a tailored model, which might well be a refined version of the current models,” says Professor Pollet. The experiments can be viewed as entangled quantum-mechanical particles and hence tantamount to an analogue quantum computer. Analogue devices must be

A key model in condensed matter physics is the electron gas with Coulomb interactions, which are relevant for density functional theory at very low temperatures, and also for warm, dense plasma at high temperatures.

Currently there is no method able to describe long-range interactions quantitatively and precisely in the strongly correlated regime While this kind of investigative work may have long-term implications for materials science and other fields, research is purely fundamental in nature at the moment, and scientists continue to investigate many-body effects in quantum systems. “This is about answering fundamental questions – how do quantum particles behave while they interact? How can we play around with this?” continues Professor Pollet.

This connection to condensed matter physics brought about a research paradigm shift: could the intractable models that are ubiquitous in condensed matter physics become solvable in a cold-atom experiment?

Could wider insights potentially be drawn from understanding those models better? As long as a model

calibrated and validated against known results prior to their use, just as an analogue watch requires specific fine tuning before it can be used.

A very successful demonstration of such validation was shown by comparing experimental time-of-flight images with the ones obtained in fully ab-initio quantum Monte Carlo simulations over a range of different temperatures and interaction strengths. Monte Carlo methods involve the stochastic evaluation of integrals in very high dimensions; Professor Pollet says some important preliminary steps need to be taken before they can be applied to a quantum model. “In order to do Monte Carlo simulations of a quantum model, you first need to map it onto a classical one. This is typically done by

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interpreting temperature as an additional dimension,” he explains. “What we could show is that for nearly all experiments of the current generation we have an almost perfect theoretical understanding. This is a unique feature of such experiments, and remains a distant dream for the traditional solid state community.”

The step towards modelling and eventually material design hinges crucially on how trustworthy the experiments are in more difficult parameter regimes than those in which they are currently operating. However, all of the numerical methods employed so successfully thus far will break down when the fermionic experiments get colder and stronger interacting. This state of affairs is wholly unsatisfactory and lays bare the urgent need for novel numerical methods. Ideally, such new methods could then be checked against the experiments and lead to a mutual validation. On top of that, the newly validated methods could then be reliably applied to other models in different fields of physics. “We hope to achieve this by exploring the potential of a novel method, diagrammatic Monte Carlo, which we will apply to some longstanding questions in theoretical physics,”outlines Professor Pollet.

A key example where progress is desperately needed is the Hubbard model, which has attracted attention as a means to describe high-temperature superconductivity and which has already been realized in a cold-atom experiment - albeit at relatively high temperatures compared to the scale where superconductivity sets in in the cuprates.

Alongside their work on these models with local interactions, Professor Pollet says the project is also interested in models of long-range interactions. “A key model in condensed matter physics is the electron gas with Coulomb interactions, which is relevant for density functional theory at very low temperatures, and also for warm, dense plasma at temperatures of the order of fermionic degeneracy. Currently there is no method that can quantitatively and precisely describe long-range interactions,” he says.

Non-local interactions can potentially also be realized in cold gas experiments: the first steps to degenerate polar molecules with a dipole interaction and Rydberg atoms have recently been reported. Another area where cold atom experiments offer a unique framework compared to other branches in physics is in the monitoring of

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quantum dynamics in real time. A major goal of the project is to develop new methods in this area that go substantially beyond the current state of the art.

Bosonic systems This will form a central part of Professor Pollet’s ongoing research agenda. The project has also pursued research into strongly interacting bosonic systems, and two main types of results have been gained from this work. “The set-up is again one of cold bosonic atoms in an optical lattice. We are looking at a critical point, the transition between a superfluid and an insulator at constant density. There were theoretically a few open questions about this critical point in two spatial dimensions, namely the nature of the collective excitations and the optical conductivity,” outlines Professor Pollet.

The project has been able to establish that an amplitude mode exists in two dimensions, not unlike the celebrated Higgs mode of the standard model of particle physics. While other researchers have gained similar results along similar lines, Professor Pollet says further work is required to validate the picture. “This is a case where we have control over the current experiment, but we would like to see experiments done again under slightly more challenging conditions, but which would be needed to verify the theoretical predictions and settle the discussion once and for all,” he says.

The second type of result relates to the optical conductivity, the response of the system to phase modulation of the lattice laser. This response is very difficult to compute numerically; in the course of this work, researchers checked the validity of the AdS/CFT correspondence. “Some people argue that conformal field theories, which is the emergent model at this critical point, can be solved more easily in a gravity dual theory in anti-de sitter space,” outlines Professor Pollet. This idea, while it has not been rigorously proven, is very appealing, as it would allow researchers to use simple perturbation theory to describe the behaviour of strongly interacting cold gases. “By doing this the mathematically ill-defined analytic continuation problem could be brought under control in a regime without small parameters. It sounds almost too good to be true,” says Professor Pollet.

“Our first results pointed out that the correspondence might work but it needs further refinement nevertheless.”

At a glance Full Project Title Quantum Simulation of Many-Body Physics in Ultracold Gases (QUSIMGAS) Project Objectives To develop new quantum Monte Carlo methods to study strongly interacting cold-atomic systems in hitherto intractable regimes.

Project Funding Funded by an ERC Starting Grant.

(Please see website for full details) Contact Details Professor Lode Pollet Department für Physik Arnold Sommerfeld Center A405 LMU München Theresienstr 37 80333 München Germany T: +49 89 2180 4593 E: Lode.Pollet@physik.uni-muenchen.de W: http://www.theorie.physik.unimuenchen.de/lsschollwoeck/pollet_ group/index.html - K. Chen, L. Liu, Y. Deng, L. Pollet, and N. V. Prokof’ev, Phys. Rev. Lett. 112, 030402 (2014) (Ed. suggestion) - L. Liu, K. Chen, Y. Deng, M. Endres, L. Pollet, and N. V. Prokof’ev, Phys. Rev. B 92, 174521 (2015) (Ed. suggestion)

Professor Lode Pollet

Lode Pollet is a Professor at the Institute of Theroretical Physics at LudwigMaximilians University in Munich. He gained his PhD from the University of Ghent in 2005, after which he worked at several universities in both Europe and America, before taking up his current position in 2011. His research interests include Monte Carlo simulations, quantum manybody problems and ultracold atoms.

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While renewable energies like solar power offer a sustainable source of energy, their very nature means it is difficult to guarantee a reliable supply. The HYSOL project is developing a new hybrid concept which will combine different sources of energy in a flexible configuration, providing a reliable supply of energy, as Lucia Gonzalez Cuadrado and Alberto R. Rocha explain

Solar hybrid technology for tomorrow’s energy supply The development of

sustainable and reliable methods of generating power is a major research priority. While renewable sources of energy like solar power hold great potential in these terms, their very nature means they do not on their own provide a reliable supply, an issue which lies at the core of the HYSOL project. “The HYSOL project is addressing problems around the supply of energy to the electricity grid in a firm way. We’re going to incorporate a gas turbine and a heat recovery system within a Concentrated Solar Power (CSP) plant, so that when there is no solar resource we can produce electricity and supply it to the grid.

Meanwhile, we also heat molten salts with the exhaust gases to increase the storage level,” says project coordinator Lucia Gonzalez Cuadrado. The current generation of CSP plants provide energy to the grid when there is sufficient solar resource, now researchers in the HYSOL project aim to develop hybrid technologies that combine CSP and biomass in a flexible configuration to help provide a more reliable supply.

“When there is no solar resource, nor energy stored in the tanks, we will use the gas turbine to provide energy to the grid. We also heat the molten salts for later use,” explains Gonzalez Cuadrado.

Molten salts These molten salts, such as potassium nitrate, sodium nitrate and calcium nitrate, are used to store the heat produced in a CSP plant, which is then used to produce steam which will rotate a steam turbine, generating electricity. While a CSP plant is comprised of

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many individual components, the project’s primary focus is on the development of a heat exchanger – HYSOL – to recover the turbine’s exhaust gases, which can then be used to heat the molten salt and thus increase energy output. “The heat recovery system will be used to release the energy coming from the gas or biogas itself to the molten Hysol demo plant installed in Manchasol (Ciudad Real). It was commissioned during the first months of 2016.

salt. This energy is stored in the molten salt, and can then be used to meet demand,” outlines Alberto R. Rocha, Head of the Technology & Innovation Department at ACS / COBRA, leader of the HYSOL project consortium. The use of the solar resource and the gas turbine can be optimised in line with the local situation, more closely matching supply with demand. “We can match energy production with demand, this

is the important thing. HYSOL is a key element of this concept,” continues R. Rocha.

The level of demand for energy is of course highly variable, and in some countries it may peak at times when the solar resource is not available. This is an issue of which R. Rocha is well aware. “For example, the solar resource will not generate enough energy in the South African winter to meet demand at cost-effective values,” he points out. A hybrid power plant addresses this issue by providing a reliable supply of energy – with a high proportion from renewable sources – at an optimised costefficiency ratio tailored to the specific nature of the local market and the local renewable resource. “With the HYSOL concept we can introduce more renewable energy onto the system. At least 80 percent of the energy produced comes from renewable sources,” says R. Rocha. “The most important thing is that this concept has to be stable, firm and reliable, capable of meeting demand. Then it can also act as a foundation for the future introduction of more renewable energy onto the system.

There are no other renewable technologies, at this time, that can provide a reliable, firm and competitive source of energy.”

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At a glance Full Project Title Hysol Plant configuration. The exhaust gases produced by the gas turbine will heat the molten salts, which can be used directly in the steam generator or stored for later use.

This represents a new concept on the market, which is very much in line with the goals set out in the European Strategic Energy Technology Plan (SET-Plan), which aims to accelerate the development and deployment of low-carbon technologies within Europe as a whole. The electricity generated from renewable sources can also be transported around Europe in a relatively efficient and cheap way. “The idea is to supply energy to different countries, in line with the Energy Union targets,” outlines R Rocha. This work again is in tune with the legislative climate, specifically the EU renewable energy sources (RES) directive of 2009, which required

Innovative Configuration for a Fully Renewable Hybrid CSP Plant (HYSOL) Project Objectives Hysol was created to become a reference in the initiatives ongoing in the CSP/biomass global market. HYSOL focuses on overcoming the CSP technology limitations to increase its contribution in the global electric market, hybridizing with biomass energy to achieve 100 % renewable energy, and providing power to the electrical grid in a stable, firm and reliable manner independently of meteorological circumstances. towards exporting what is European innovation, European technology, to other countries. This is a very important aspect of this project,” he stresses. Several markets are being studied within the project – South Africa, Saudi Arabia, Chile, Mexico and certain parts of Europe – with a view to the eventual adoption of the HYSOL technology; understanding the local market is a crucial step in this regard. “For example, the South African government pay 2.7 times more for energy during the peak hours in the evening than the rest of the day. This is to give an extra value to the Dispachtabilty and Firmness” outlines R Rocha.

The HYSOL project is addressing problems around the supply of energy to the electricity grid. We’re going to incorporate a gas turbine within a Concentrated Solar Power (CSP) plant, so that when there is no solar resource we can produce electricity with the Gas Turbine Member States to set national targets for increasing the contribution that renewable energy sources make to total consumption by 2020. “If we can establish an EU energy market, we can use wind energy in the north of Europe, and complement it with solar energy from Southern Europe, thereby reducing Europe’s energy dependence on fossil fuels” explains R. Rocha.

Energy independence This is a key goal of many European states, yet the nature of the research involved often demands close collaboration between international partners. The project consortium itself brings together eight partners from four different EU Member States, and R. Rocha says they are beginning to look towards the commercial application of their research. “Our intention is to do a demonstration plan in Europe – to demonstrate in Europe that this technology works. After that we will look

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This kind of knowledge will be key to ensuring that CSP plants are cost-efficient, and can meet the needs of the market in which they are located. The HYSOL demonstrator has been installed in the innovation cluster located next to an existing ACS / COBRA CSP plant in Alcazar de San Juan Spain, with the aim of validating the technology in terms of its technical, economic and environmental performance.

“This is the first prototype, to demonstrate that this technology works effectively,” says R Rocha. The development of a CSP plant is a capital-intensive project, with the majority of the costs front-loaded at the beginning; however, R Rocha believes it can lead to long-term dividends. “The target is to optimise the technologies, in order to provide a reliable supply of energy at a competitive price. The important thing is the value of the energy,” he says. “The sector is now working to demonstrate the value of CSP .”

Project Funding Project financed by the European Commission under the Seventh Framework Programme.

Project Partners ACS / COBRA leads the HYSOL Consortium, formed by another 7 European partners: PSA-CIEMAT, IDie, AITESA, ENEA, DTU, UPM AND SDLO-PRI. Contact Details Lucía González Cuadrado, T&I Lead Engineer COBRA Energía, Technology & Innovation C/ Cardenal Marcelo Spínola, 6 28016 – Madrid T: +34 628 775 462 E: luciagonzalez@grupocobra.com W: http://www.hysolproject.eu/

Alberto R. Rocha

Lucía González Cuadrado

Alberto R. Rocha has an extensive experience in Renewable Energy Business. During the last 10 years, Alberto has been working in the most important companies of the sector, bearing responsibilities in both areas, R&D developments and Renewable Energy Finance.

Currently, Alberto is the Head of COBRA Technology and Innovation Business Unit.

Lucía González Cuadrado. Member of the Technology and Innovation Department in COBRA. She has worked in leader companies of the CSP sector, mainly in the R&D area but also as construction and commissioning supervisor in commercial plants. Since her integration in the T&I department in COBRA Lucía has been involved in different R&D projects of CSP technologies.

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Material Matters – How Solid State Research Underpins Innovation Some of the more exciting machines we have invented in modern history have been forged with research derived in solid state physics; think particle accelerators, MRI scanners and even floating trains. Beyond these inventions, we look at how we can use studies in this field for advancing efficient energy use and quantum computing

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n layman’s terms, solid state physics is the study of rigid materials and their properties at an atomic level – properties such as elasticity and hardness – which in turn can give rise to functionality for the material. This is essentially the theoretical foundation for materials science and can have implications in a range of applications, such as for high resolution microscopy, 3D imaging, solar cells, low friction materials, data storage systems, quantum computing and a raft of technologies that can benefit society. Studies have shown that around 70% of all technical innovations are either directly or indirectly attributed to the materials they use, so it’s little surprise that this is a thriving area of scientific research in Europe and around the world.

Solid state physics particularly deals with the physical and structural properties of crystalline solids, like semiconductors.

There have been plenty of new discoveries in the realm of solid state physics.

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Why is superconductivity useful?

A major payoff from research in solid state physics is in discovering super conducting materials. When there is zero electrical resistance and the ejection of magnetic field flux in various materials, this is called superconductivity. Initially it was thought it could only occur when the materials were cooled below a critical temperature close to absolute zero. However, Nobel prize glory came to Georg Bednorz and K Alex Muller in 1987 for discovering that a material composed of copper dioxide with lanthanum and barium additives became superconducting at a much higher temperature. This discovery ignited further scientific curiosity and investigations – and this curiosity hasn’t waned today. The raised temperature is important as it is a critical factor to costs in industrial uses. It means that the cooling process can be cheaper. For instance, liquid nitrogen can be used to replace liquid helium – which is a lot more cost effective and can even be produced in some circumstances on-site. It’s safer too.

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that nearly 40% of venture capitalists interviewed said they would willingly invest at the early stages in advanced materials dedicated to the energy sector.

Advanced materials, advanced machines

The ultimate dream for those investigating superconductivity is that we will one day be able to achieve it at room temperature.

Superconducting is useful because it means a lot less energy is wasted and electricity delivery is faster. If you have electricity without resistance at room temperature – it could revolutionise energy distribution and everyday usage. It would have tremendous impact on efficiencies worldwide.

Research into superconductivity has been pivotal to the development of some of our most useful scientific instruments. For instance, superconducting magnets are powerful electromagnets and are used in MRI (Magnetic Resonance Imaging) /NMR (Nuclear Magnetic Resonance), mass spectrometers and magnets that guide beams in particle accelerators. Superconductors are also used in superconducting quantum interference devices.

Trains can float on superconducting devices. The Shanghai Maglev Train in China, developed by Siemens, can travel 30km in 8 minutes – travelling at a maximum speed of 430km/h. Each carriage of the train has superconducting electromagnets made from niobium-titanium alloys underneath it. In contrast to most high temperature superconductors these can be formed into wires.

There are no rails for it to use like a traditional train, instead, there is a guiding path that is lined with conducting wire coils which produce temporary electromagnetic fields when the train flies over them. The magnetic field on the train, which is moving – then produces a current in them. The coils create a repulsing magnetic field that levitates the train.

There is huge potential for solid-state research to make a real difference and industry knows it. The global market value for advanced materials is projected to be EURO 1100 billion by 2050.

The pursuit of efficiency in energy

Breakthrough in superconductivity

There are projects under the mantel of solid state physics that are currently looking into creating efficiencies in solar cells, to lower development costs and improve their performance. Several universities in Europe are involved in research. Research carried out at Imperial College in London, looks at organic photovoltaic materials like conjugated polymers, fullerenes and nanoparticles from solution. The Max Planck Institute in Germany is using solid state research to investigate harvesting solar power and also longer life batteries for electric cars.

Discovering advanced materials for applications in energy is big business too. A European Commission study entitled: Technology and market perspective for future Value Added Materials, stated

In August 2015 the Max Planck Institute for Chemistry and Johannes Gutenburg University, announced that a team led

by Mikhail Erements had made a major breakthrough with superconductivity based research. They found that hydrogen sulphide loses electrical resistance under high pressure at minus 70 degrees Celsius. The substance was placed under pressure of a staggering 1.5 million bar – equivalent to half the pressure of the Earth’s core – a pressure so phenomenal that only diamond could

Studies have shown that around 70% of all technical innovations are either directly or indirectly attributed to the materials they use, so it’s little surprise that this is a thriving area of scientific research in Europe and around the world.

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resist it. The apparatus that the team used was very versatile.

Researchers simply pressed a metal cell with allen screws together but this caused incredible pressure within the cell.

Prior to this research the best superconductors were made of special coper ceramic called cuprates. The transition temperature (where electrical resistance is lost) was minus 140 degrees Celcius at normal air pressure and minus 109 degrees Celcius at high pressure.

The research by the team at the German universities in comparison, set a new record for superconductivity but more than this, their findings highlighted a potential new way to transport current at room temperature with no loss – which is a huge step.

The research showed that many hydrogen-rich materials can have a high transition temperature.

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Toward quantum computers Quantum computers, that harness the strange properties of quantum physics, would make computers capable of a processing power almost beyond comprehension. Processing tasks that current supercomputers would take years to complete could be done in moments with a quantum computer – the technological applications would be world changing. It would be able to perform at such high levels that it could accelerate the speed of our progress as a civilisation. The theory behind constructing a quantum computer is established. Currently, researchers have demonstrated that they can even build the units of a quantum computer, known as qubits but the challenge is now to make them perform together in a way that will create a fully working computer. Whereas computers rely on transistors that can give

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Trains can float on superconducting devices. The Shanghai Maglev Train in China, developed

by Siemens, can travel 30km in 8 minutes – travelling at a maximum speed of 430km/h. a value of 0 or 1, cubits can be a 0 and 1 at the same time which means they can process vast amounts of operations in the same time a traditional computer performs just one.

Part of the challenge is in the materials science – and that is where solid state physics research comes into play. The basic microchips of a computer will need to be wired together in a way that is still being worked out. Quantum states are very delicate – they are destroyed by heat and electromagnetic noise which means they don’t last long. Currently, superconductors made from aluminium are needed to be chilled to just above absolute zero to make possible the quantum effects in the first place.

There are many different approaches to creating quantum computers. Some focus on using the spin of individual particles, like atoms, molecules and photons and they are robust against interference but they need very large apparatus – not great if you want to use many qubits. For solid state designs, scaling up is not a problem but they are more susceptible to electromagnetic interference. This is why hybrid systems are being seen as a good approach to get the best of each system. There is a realisation that a connection is needed between the most advanced transistor technology and the emerging quantum computing approaches.

Progress in this important study is being seen as part responsibility of solid state research teams. In the decade to come, a number of new technologies is envisaged based on quantum computing functionality. We might live in an age where cars negotiate complex busy traffic by themselves or planes compute the safest decisions for flight. We could be finding new planets in the cosmos instantaneously from a mass of data, or rely on precision

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weather forecasting. In healthcare we might also be able to develop and design more effective drugs at far quicker rates.

Processing big data will take no time at all, which means rates of discovery and design can be greatly accelerated.

Changes of approach in solid state research Something very new in the way we investigate solid state research has just happened. An international team led by physicist Mark Sherwin of UC Santa Barbara recently announced in the journal Nature, that what the Large Hadron Collider has done for particle physics – such as discovering the Higgs Boson particle – it can do for solid state research. They realised that basic concepts of the collider can be applied to this branch of physics to potentially lead to new discoveries. We need to know the structural and electronic properties of solids to facilitate technologies, so using the same concepts as particle physics can really be a game-changer.

Within a solid, analogs to particles like protons are called quasiparticles. The researchers created quasiparticles called excitons and accelerated them using unique laser beams that enabled researchers to observe quasiparticle collision events. The collisions were produced within excitons in a thin flake of tungsten diselenide. With recollisions, ultrashort light bursts were generated that encode key information of the solid. This method may give scientists a tool for clarifying existing mysteries in solid state research, provide more insight into phases of matter in high temperature superconducting and ultimately lead to better designed materials.

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Numerical methods that lead to new insights Numerical methods are key tools in the study of hyperbolic partial differential equations, which can be used to model many interesting physics and engineering systems. We spoke to Professor Siddhartha Mishra about the SPARCCLE project’s work in developing a framework that will dramatically increase the range and scope of numerical simulations A wide range

of physical phenomena can be modelled using partial differential equations (PDEs), including electrodynamics, weather systems and fluid flow. While these equations hold broad relevance, researchers in the SPARRCLE project are investigating a specific sub-class of PDEs. “We are interested in a sub-class of these PDEs called hyperbolic partial differential equations. The problems we’re interested in come overwhelmingly from the fluid dynamics field, from the challenge of describing fluids, such as gases, water, and plasmas,” says Professor Siddhartha Mishra, the project’s Principal Investigator.

The behaviour of many of these fluids can be described in terms of a particular type of hyperbolic partial differential equation called systems of conservation laws. However, these hyperbolic partial differential equations are very complex, and can’t be solved using established formulas. “They are non-linear – so small changes can lead to a large change in what you’re trying to describe,” explains Professor Mishra. Researchers are using numerical methods to study these equations. “We have to use numerical

methods in order to simulate, calculate or approximate the solution of these equations, in order to then solve them on a computer,” continues Professor Mishra.

These PDEs cannot be precisely solved, so it is necessary to include some approximations, which lead to numerical errors. This forms a key area of the

Physical problems These kinds of physical and engineering problems are often highly complex, with discontinuities such as shock waves and solutions that depend on underlying small-scale effects. Such problems are beyond the range of existing simulation methods; by incorporating more

sub-class of PDEs called hyperbolic partial differential equations. The We are interested in a

problems we’re interested in come overwhelmingly from the fluid dynamics field, from the challenge of describing fluids, such as gases, water, and plasmas project’s research agenda. “The main goal of this project is to control, minimise and describe these numerical errors,” says Professor Mishra. The project’s work is primarily fundamental in nature, yet it holds real importance to the potential application of numerical methods to complex physical and engineering simulations. “We aim to develop a simulation platform for a whole range of applications. It’s more fundamental than one particular application,” outlines Professor Mishra.

information about these small-scale effects, Professor Mishra aims to control numerical errors and quantify the uncertainty of a mathematical model. “We are mostly interested in describing phenomena at medium and large scales,” he continues. “Take the example of the propagation of a tsunami, which is a wave generated by an earthquake. The water rises up, then the wave flows, moves through the ocean and hits land.”

The main interest here is in issues like the amplitude and speed of the wave.

A simulation of the statistics of the wave height for the Lituya Bay, Alaska, mega tsunami of July 9, 1958 using a Multi-level Monte Carlo finite volume method, developed within the SPARCCLE project. The colorbar represents wave height in meters. Left: Mean Right: Variance at 39 seconds after rockslide

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“We’re interested in the amplitude of the wave, and we’re interested in the wave form and how it propagates. Is it radial? Is it not radial? These are the things that really matter,” says Professor Mishra.

“Once the wave reaches the shore, we’re interested in more detail – for instance, you’re interested in what the height of the wave will be at a certain point.”

Researchers need initial data on this scenario in order to model it effectively. In the case of a tsunami, researchers can only get an approximate value on how far the water initially rose, while there are also further uncertainties. “We can make measurements, but there are statistical errors, while the equations themselves have incomplete parameters. In a tsunami simulation, there are certain parameters that we cannot measure,” explains Professor Mishra. While it is not currently possible to predict the height of a tsunami wave, Professor Mishra says that improved numerical simulations could help understand its potential impact. “You can calculate the probability that a tsunami wave is going to lead to a wave with a height of more than 1 metre in a specific location,” he says.

This kind of information would be highly valuable to engineers and building designers in assessing the probability of failure, underlining the wider importance of Professor Mishra’s research. These kinds of simulations require not only sophisticated numerical methods, but also high computing power. “It’s only relatively recently that we’ve been able to get the data, the numerical methods, and the computing capacity to provide these kinds of risk maps or design probabilities. This wasn’t previously possible,” says Professor Mishra. The codes developed within the

project will also be made publicly available to scientists and engineers. “Several codes have been designed as a part of this project,” continues Professor Mishra.

Numerical simulations These codes will dramatically increase the range and scope of numerical simulations, helping to address some major social challenges. One of the codes that Professor Mishra has been working on over the last decade or more is designed for astrophysical applications, while further codes are being developed. “There are different codes for different domains. We have codes for astrophysics, we have codes for tsunami simulations,” he explains.

Further potential domains have been identified, including climate dynamics and exoplanets, earth-like planets beyond our solar system. “There’s a lot of interest in the astrophysics community in detecting and understanding exoplanets, and also in simulating the climate of an exoplanet,” says Professor Mishra.

A lot of money is being invested in better telescopes to detect these exoplanets, and several thousand have been detected over the past two decades. Researchers have been able to gather data about the climate of these planets. “Inferences about their climate can be drawn from astrophysical signals. We can measure these signals,” outlines Professor Mishra.

From this data, researchers can then try to build a fuller picture of their climate dynamics. “It’s possible that these planets are habitable; is there water? What sort of atmosphere do they have? ” says Professor Mishra. “To answer these questions, it’s essential to simulate the climate of these exoplanets, so that we know what we are trying to search for.”

At a glance Full Project Title Structure Preserving Approximations for Robust Computation of Conservation Laws and related Equations (SPARCCLE).

Project Objectives To design and implement robust and efficient numerical algorithms for approximating nonlinear Partial differential equations, in particular hyperbolic systems of conservation laws, that describe complex fluid and plasma flows. The proposed algorithms are designed to imitate structural properties, satisfied by solutions of the underlying equations.

Project Partners Ulrik S. Fjordholm (Norwegian University of Science and Technology, Trondheim), Eitan Tadmor (University of Maryland, USA), Philippe LeFloch (University of Paris VI, France), Manuel Castro (U. Malaga, Spain), Tapio Schneider (Caltech, USA).

Contact Details Professor Siddhartha Mishra, Seminar for Applied Mathematics (SAM), D-MATH, ETH Zurich, Switzerland T: +41 44 632 7563 E: siddhartha.mishra@sam.math.ethz.ch W: https://www.math.ethz.ch/sam/ research/projects.html?details=34

Professor Siddhartha Mishra

Professor Siddhartha Mishra is currently professor for Applied Mathematics at the department of mathematics, ETH Zurich.

Born and educated in India, Prof. Mishra’s research interests are in the areas of numerical analysis, scientific computing and applications to computational fluid dynamics and computational astrophysics.

His work has resulted in about 75 published papers and he has received awards such as the Richard von Mises prize of the international association of applied mathematics and mechanics.

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Many researchers spend time abroad during their careers as they widen their experience and deepen their knowledge. The BeIPD COFUND scheme offers post-doctoral fellows the opportunity to live and perform state-of-the-art research in the heart of Belgium, helping young researchers to build their careers in academia, as project responsible Isabelle Halleux and Raphaela Delahaye, project manager explain

Building the foundations of tomorrow’s research The University of Liege

has a long history of welcoming international researchers, with a number of fellowship programmes offering researchers the opportunity to live and study in the Belgian city. The BeIPD-COFUND scheme, an initiative launched in 2013 with support from the European Commission, builds on this tradition, strengthening research links and helping post-doctoral fellows to develop their academic careers.

“With this funding we could extend the duration of the fellowships, from one year as offered in the earlier Incoming PostDocs (IPD) scheme, to two years. A second important point is that, with the support of the European Commission, we can look to implement new selection and evaluation practices,” says Project Responsible Isabelle Halleux.

This includes the introduction of external reviewers in the evaluation process. Each application is now reviewed by two internal and two external reviewers, so that different perspectives are taken into account in assessing potential research projects. “The top priority is of course the excellence of the application,” stresses Halleux. Alongside looking at an applicant’s academic credentials, reviewers also look at the extent of their previous research collaborations, which Delahaye says is an important consideration. “If we feel that they have already established relationships with other researchers, they have a better chance of getting a fellowship. Then, during their fellowship here in Liege, they can develop their network further. They can go and see people, invite them to Liege and organise conferences,” she outlines.

A researcher who is part of a strong network of collaborators can exchange knowledge and ideas with their peers, which opens up new avenues of investigation, fitting in with the BeIPD

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Pictures taken at the Annual Inbound Researcher Welcome Meeting. © Michel Houet

scheme’s wider commitment to fostering independent research. While much scientific research is collaborative in nature, Halleux says BeIPD is very much ‘bottom-up’, with researchers encouraged to work autonomously. “Many of the best applicants already have a good research network. They might already know which Professor they’d like to work with,” she says. These fellowships are offered across all research disciplines, which are grouped within the social sciences, health, and science and technology sectors. “In practice, we receive less Health applications than Social Sciences/ Science and technology applications,” says Delahaye.

Networking opportunities begin from the very first moment of arrival. © Michel Houet

Extended duration The two-year duration of the fellowships gives researchers the opportunity to really get their teeth into a project, which was not always the case previously. The University conducted a survey of researchers who had completed their fellowship under the former IPD scheme, and their feedback was clear. “The fellows said that with the challenge of moving to a new country and getting to know the culture and the people, combined with research and other pressures, they had a hard time completing their projects. With a two-year fellowship, they are able to complete the project in the way they intended,” says Halleux. There are also regular meetings among fellows, along with the opportunity for a little socialising, which always helps people feel welcome in a new country. “We think it is important that research fellows are connected to the city and the region,” says Halleux.

The Wallonia region in which the University is located provides a lot of funding for private-public partnerships, and Halleux is keen to help foster close

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links with industry. Regular meetings are held with local businesses, so that researchers can hear from professionals outside the academic sector and widen their experience. “There are meetings with executives and people working on economic strategies. We also hold meetings with people working in technology transfer, together with researchers, including not just incoming post-docs, but also PhD researchers and Professors,” outlines Halleux. The University also works closely with Liege Science Park, which is home to a number of spin-off enterprises. “There are a lot of

There has also been positive feedback from the researchers themselves, which has helped bolster the University’s international reputation. “The scheme helps us get more recognition on the international level,” continues Delahaye.

Research opportunities There are now plans to further enhance the project in the years ahead and extend research opportunities to the next generation. While the scheme continues to attract large numbers of high-quality applicants, Delahaye says there is room for improvement. “We

With this funding we can extend the duration of the fellowships, from one year as offered in the earlier IPD scheme, to two years. A second important point is that, with the support of the European Commission, we can look to implement new selection and evaluation rules and enhance the existing ones companies and spin-offs based at the Liège Science Park, and their representatives are also invited to our meetings,” continues Delahaye.

The scheme has also gained wider acceptance among academic staff since its launch in 2013. While most Professors at the University of course have long experience of working with post-doctoral fellows, they typically had to apply for funding themselves, whereas under the BeIPD-COFUND scheme the money comes from institutional/ EU resources. “We have seen a big difference internally since the start of the project,” outlines Delahaye.

During the Inbound Researcher Meeting, participants take an active part in the welcoming activities. © Michel Houet

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have some ideas about how the evaluation process could be improved, and we are also thinking about how we could let applicants know about the progress of their application while it is being considered,” she says. Delahaye and her colleagues are also working to integrate the European Commission’s Open Transparent Merit-based evaluation (OTM-R) package of tools on the recruitment of researchers.

“There is a shortlist of things we can do to implement the OTM-R package, which complements our HR strategy for researchers,” explains Delahaye.

At a glance Full Project Title Be International Post-Doc - (BeIPD) Project Objectives The University of Liege (ULg) has run an international Incoming postdoctoral fellowship programme for years (2006-2012) with excellent results: 120 fellows, hundreds of joint publications, lots of professional and transferable skills attendees. Fellowships are based on a bottom-up approach of the fellows.

Applicants define their own research project in cooperation with their host unit, so that they can develop a win-win cooperation in terms of science, excellence and career development.

Project Funding Almost 17 million euros budget: 40% contribution from the EU, 60% of own financing from the University of Liège. MSCACOFUND grant number 600405. With financial support from the European Commission.

Project Partners 477 incoming applications and 80 outgoing applications registered (last 3 calls). More than 900 interational experts contacted since the start of the project in 2013. More than 230 experts that we work with on a regular basis.

Contact Details Raphaela Delahaye, BeIPD-COFUND Project Manager, UNIVERSITE DE LIEGE Administration Recherche & Développement Place du 20 août 7(bât A1)| B-4000 Liège, Belgium T: +32 4 366 91 04 E: beipd@ulg.ac.be W: www.ulg.ac.be/cofund

Dr Isabelle Halleux

Dr Isabelle Halleux is the Director of the Administration R&D Department at the University of Liège, dealing with research strategy and funding, doctoral affairs and project development. Her administration manages various FP7-People-projects. She supervises the EURAXESS initiatives (EURAXESS jobs, services and HR strategy) at ULg and is actively involved in the Euraxess network in Europe. She is coaching several universities in the implementation of the Charter and Code, acts as facilitator in the EU cohorts and is peer reviewing HRS4R-acknowledged institutions (on behalf of Deloitte and Vitae, UK). She was member of the development staff of the on-line course PSRL (Professional Skills for Research Leaders) and organises career development trainings for PhD students and staff in Europe as well as in Africa and East-Asia.

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The network of filaments in the star-forming cloud IC 5146 as imaged by the Herschel Space Observatory as part of the “Gould Belt survey” key programme (colour composite: 500/250/70 μm).

Stellar observations open a window on star formation The question of how stars formed remains one of the major unsolved problems in modern astrophysics. Project Coordinator Dr Philippe André tells us how the ORISTARS project is combining observational, theoretical and instrumental research to gain new insights into how stars form, work which will have significant scientific implications The process of star formation is closely linked to both the evolution of galaxies on large scales, and the formation of planets on small scales. Based at France’s Alternative Energies and Atomic Energy Commission, Philippe André is the Principal Investigator of the ORISTARS project, an ERC-backed initiative combining observational, theoretical and instrumental research to investigate the process by which stars are formed. “The general goal of the project is to understand the process of star formation, and also the formation of solar systems, together with their surrounding planets,” he says. This research builds on the results gained by the Herschel Space Observatory, which was launched in 2009 and continued to operate until April 2013. “The space observatory investigated sub-millimetre wavelengths. The reason we want to observe sub-millimetre wavelengths is that stars form in cold molecular clouds, and we need to observe sub-millimetre wavelengths to investigate the very cold objects involved in star formation,” continues André.

This is a highly complex process, as a proto-star acquires mass from a molecular cloud and gradually evolves over time. A star can be broadly defined as an

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astronomical body that can generate its own energy; this characteristic develops over time, as a proto-star steadily gains mass, to a point where it is capable of nuclear fusion. “The mass of a proto-star is very small. The central object of the protostar gains mass from the surrounding prestellar condensation, which itself lies in a filament. So a proto-star achieves its final mass when the central object has eventually

The development of the Herschel Space Observatory represented an important breakthrough in observational studies of these processes.

Sub-millimetre wavelengths cannot be observed from the ground, yet with Herschel, scientists were able to image molecular clouds, gaining unprecedented levels of detail.

“What the results revealed, very early on, is the widespread presence of

With Herschel we took a census of these prestellar cores. We realised from our observations that they were all associated with filaments, so a direct connection was established between star

formation and the filaments accreted all of the mass of the initial prestellar condensation,” explains André. The pre-main sequence phase is another important stage in the development of a star. “The star is no longer a proto-star at this point, but it’s not yet a normal star either. In this phase, the object contracts progressively, and as it contracts it warms up, until the temperature at the centre reaches 10 million degrees and it is capable of nuclear fusion. At that point it becomes a normal star,” says André.

filamentary structures in these clouds.

The images revealed the texture of the clouds at high levels of detail,” explains André. These filamentary structures appear to play a key role in the star formation process, while researchers have also established links between these structures and pre-stellar cores, the progenitors of stars in the clouds.

“With Herschel we took a census of these pre-stellar cores. We realised from our observations that they were all associated

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Formation of filamentary molecular clouds

ORISTARS group picture

Fragmentation of dense filaments into pre-stellar cores with filaments, so a direct connection was established between star formation and the filaments – this was an important breakthrough from the Herschel observations,” outlines André.

New paradigm These observations form the starting point for the ORISTARS project. The Herschel observations led to what André calls a new paradigm for our understanding of star formation and inter-stellar filaments. “Filaments formed first in the inter-stellar medium, and then these filaments fragmented to pre-stellar cores and formed stars. The project is exploring the details of this new paradigm,” he says. There are three main lines of research within the project. “We are investigating filament formation, the fragmentation of these filaments into pre-stellar cores, and then, on smaller scales, the sub-fragmentation of these pre-stellar cores into binary stars and protoplanetary disks,” continues André.

“There is a connection between these scales, and we are trying to address this in our research. There is also an instrumental component to the project, which is the development of a mm-wave

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polarimeter. This will enable us to learn about the magnetic field inside these filaments, and to better understand the role of magnetic fields in star formation at these scales.”

These three core lines of research are closely linked. Evidence suggests that magnetic fields are a major factor in the formation of filamentary molecular clouds. “Evidence on large scales suggests that the magnetic field tends to be parallel to the low-density filaments, the filaments that we can see with the Herschel Space Observatory. We know this for instance from results from Planck, another satellite launched at the same time as Herschel,” says André. Magnetic fields are also thought to play a crucial role in the formation of protoplanetary disks, another important aspect of the project’s research. “We have observed that the disks around proto-stars do not form as quickly as numerical hydrodynamic simulations of proto-stellar collapse would predict. It is becoming clear that magnetic fields play an important role in controlling the formation of these disks,” continues André. “There is likely to be a connection here with the filaments on larger scales.”

Researchers are investigating how these disks form and grow. Rotation in pre-stellar condensations is thought to be a primary cause of the initial formation of protoplanetary disks. “These pre-stellar condensations have some degree of angular momentum, and as they collapse to form a proto-star, angular momentum is conserved. We realise now that this momentum is probably linked to the formation process of the filaments on larger scales. The magnetic fields that play a role on a small scale inside these proto-stellar systems, these pre-stellar condensations, are inherited from the large-scale magnetic fields in the clouds,” says André. Researchers have some information on the large-scale magnetic field, but cannot currently resolve the magnetic field within the filaments where stars form. “This is something we would like to investigate with future instruments, including this new polarimeter that we are helping to develop for a groundbased observatory, the IRAM 30m telescope, located near Granada, in Southern Spain,” outlines André.

Further data There are also plans to use data from other telescopes and observatories to

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At a glance

Collapse and sub-fragmentation of individual pre-stellar cores into systems of protostar(s)

Full Project Title Toward a Complete View of Star Formation: The Origin of Molecular Clouds, Prestellar Cores, and Star Clusters (ORISTARS) Project Objectives Understanding star formation from large to small scales is a major unsolved problem of modern astrophysics, fundamental in its own right and having a profound bearing on both galaxies and planet formation.To achieve a breakthrough in our observational and theoretical knowledge of star formation, the project confronts numerical simulations with observations obtained with state-of-the-art instrumentation, including instruments developed by our group.

Project Funding ERC-AG-PE9 - ERC Advanced Grant Universe sciences.

Contact Details Project Coordinator, Dr Philippe André Laboratoire d’Astrophysique de Paris-Saclay (AIM), Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), France T: +33 1 690 89265 E: philippe.andre@cea.fr W: http://cordis.europa.eu/project/ rcn/103194_en.html W: http://irfu.cea.fr/en/Phocea/Vie_des_ labos/Ast/ast_technique.php?id_ast=3627 W: http://gouldbelt-herschel.cea.fr W: http://ipag.osug.fr/nika2/Welcome.html http://sci.esa.int/herschel/48623-herschel-unravelsthe-thread-of-star-formation-in-the-gould-belt/ http://herschel.cf.ac.uk/news/herschel-links-starformation-sonic-booms http://sci.esa.int/herschel/55942-herschels-huntfor-filaments-in-the-milky-way/ http://www.eso.org/public/news/eso1341/ and http://www.eso.org/public/images/eso1341a/

Dr Philippe André Dr Philippe André is “Director of Research” at the Astrophysics Laboratory of the French Alternative Energies and Atomic Energy Commission (CEA), located in Saclay near Paris (France). He has over twenty-five years of experience in millimetre/submillimetre observational studies of star formation. He led the team that discovered « Class 0 » protostars the youngest known stellar bodies - and wrote several review papers on the earliest stages of star formation. He is PI of the Herschel Gould Belt Survey, one of the largest key projects on the Herschel Space Observatory and of the CALYPSO large program with the IRAM Plateau de Bure interferometer. He is also PI of the ArTéMiS submillimetre bolometer-array camera for the APEX 12-m telescope, and co-I of the NIKA-2 Kids-array camera for the IRAM Granada 30-m telescope, with a particularly strong involvement in its polarization channel.

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gain further insights. One major facility of interest is the ALMA (Atacama Large Millimeter/submillimeter Array) interferometer, a state-of-the-art array of telescopes located high in the Chilean Andes. “The ALMA facility is very interesting, as we hope it will allow us to study the details of individual protostellar systems at high angular resolution. With Herschel, we already have a lot of details on the large scales – ALMA is a very powerful tool to study the smaller scales in particular.

So the data from ALMA is very complementary,” says André. These kinds of observations are also relevant in terms of the project’s work on numerical simulations of molecular clouds. “We’re trying to simulate the formation and evolution of these molecular clouds, and the formation of structures inside these molecular clouds.

These simulations are designed to reproduce the filaments that we see in observations,” explains André.

This work is central to building a deeper understanding of molecular clouds and star formation. While observational data can offer a snapshot of the clouds, simulations provide more of a dynamic insight. “With simulations, you can in principle see exactly what happens. You have a view of how things change, and an understanding of the dynamical evolution of these molecular clouds,” points out André. These numerical simulations are being refined on an ongoing basis and confronted with observations, as researchers seek to improve accuracy and deepen their understanding of star formation. The project’s research will also feed in to other initiatives; a 1.2mm polarimeter is being developed for NIKA2, a next generation instrument to be placed at IRAM’s 30 metre telescope at Pico Veleta near Granada. “This is a polarisation channel for NIKA2, which is being commissioned at the moment, on the 30 metre telescope. This will be a concrete outcome from the project,” says André.

Network of filaments in the diffuse, non-star-forming cloud ”Polaris flare” as imaged by Herschel at 250 μm.

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