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Utrecht Life Sciences English edition | December 2017 | NewScientist.nl

A production of

Top science is a team sport


Graduate School of Life Sciences “My reason for choosing this Master’s was that I wanted to experience my future career during my Master’s – and I did. At the Graduate School of Life Sciences the environment is intimate, informal and everyone knows each other. This is incredibly helpful in finding a job.” Colinda Scheele, former student of the Master’s programme Cancer and Stem Cell Biology

uu.nl/masters/en Study at the heart of life sciences research At the Graduate School of Life Sciences (GSLS) we offer intensive research master’s programmes for ambitious students who are ready to join the academic community of Utrecht University and the University Medical Center Utrecht. Students conduct research projects at internationally renowned research groups

which are on the forefront in their field. All our master’s programmes are embedded in the research focus areas of our institutions and train students to become the multidisciplinary professionals of the future. Many students take the opportunity to gain an international experience in complementary research field at a partner institution abroad.


firstly ULSspecial

Read more about Utrecht Life Sciences on www.utrechtlifesciences.nl

Joining forces

Wouter Dhert

Mariëtte Oosterwegel

Lifting the curtain on Life Sciences The diversity of Life Sciences research in Utrecht beautifully mirrors the long and rich history of Utrecht University, and its strategic and collaborating partners, conjoined since 2010 in Utrecht Life Sciences. In Utrecht’s Science Park you’ll find not just excellent scientists, but advanced technology platforms and innovative startups as well. Moreover, Utrecht Science Park enables researchers and companies to find one another more frequently and more effectively. For science is not a solo endeavour, but a team effort. Working closely together, we can continually expand our boundaries in Utrecht, and excel in our research. The stories in this special provide a look behind the scenes, into our researchers’ lives, their widely varied areas of work and mostly, into the importance of working together. A great example is the profile of Alexander van Oudenaarden, winner of the 2017 Spinoza Prize, in which his Utrecht colleagues explain why he is so

good at what he does and such a pleasure to work with. Or the article in which Bart Spee takes us along on his work day, introducing us to his fascinating research into stem cell therapies. A final example is physician-oncologist Miriam Koopman’s story. For a week, she kept track of her activities in a diary. In doing so, she demonstrates how she manages the extraordinary combination of her work as a medical doctor with her research into bowel cancer. After reading all of these impressive tales, I am certain you’ll understand why I am so proud of what we have built together in Utrecht. We have made a world-class campus. And jointly we strive, every day, to create sustainable solutions for our constantly changing world, and work towards a healthy future for generations to come.

Wouter Dhert President, Utrecht Life Sciences www.utrechtlifesciences.nl

The Hubrecht Institute was one of the first knowledge institutes to move from Utrecht’s urban core to the more remote Uithof, in 1964. The surroundings there consisted of sprawling meadows and full view of the distant Dom tower. Fast forward to 2017, tens of thousands of students, employees and visitors make their way through the dynamic spaces of Utrecht Science Park ‘The Uithof’, its skyline punctuated by modern architecture and cranes. The Hubrecht Institute performs fundamental research into developmental biology, and attempts to understand what happens on a cellular and molecular level as a fertilized egg cell develops into an adult individual. Later, stem cell research was added by Hans Clevers, then president of the Institute. Since then, the Hubrecht Institute has grown considerably, to twenty research groups today. Since 2000, the Westerdijk Institute has been housed in the original Hubrecht laboratory. This institute manages and researches the largest collection of living fungi in the world. This year, forty new species were collected from Dutch soil samples by visitors to the Utrecht University Museum as part of the project ‘World fame, a fungus with your name’. The Hubrecht Institute and the Westerdijk Institute are part of the Royal Dutch Academy of Sciences (KNAW) and of the Utrecht Life Sciences (ULS) alliance. What makes ULS so wonderful and unique is the way it allows cooperation and shared use of research facilities by researchers from different partners (Utrecht University, University Medical Center Utrecht, Hogeschool Utrecht, KNAW, as well as many companies) and across disciplines, to answer fundamental questions about sickness and health. This New Scientist special showcases some of the most exciting examples of the research done at ULS. Who could have expected in the sixties that the Uithof would grow into such a place of wonder?

Mariëtte Oosterwegel Follow us on Twitter twitter.com/ NewScientistNL

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Operations director, Hubrecht Institute and Westerdijk Institute (KNAW)

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Talent 08 Profile Spinoza Prize awardee Albert Heck is a pioneer as well as a born organiser. 12 Mini-organs Hugo Snippert snaps cell development in colourful images.

Insight 24 What they do Calfs’ guts, sugar coats or a peek into a living cell: just another day on the job for these four scientists.

06 Overview At Utrecht’s Science Park, various disciplines can be found within walking distance from one another.

26 Profile Playing the guitar takes first place, for Spinoza Prize laureate Alexander van Oudenaarden, but hard data-analysis makes a good second.

14 Report A day on the job of Bart Spee may take you to a cell culture lab and animal facilities as well as the board room. 18 In focus Mini-intestines, up close. 30 Insight  Extraneous factors are the culprits targeted in the Exposome project.

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COVERPHOTO: IVAR PEL

20 Bart Spee ‘Aagje is the second dog to have cultivated stem cells re-introduced to her liver.‘

Opinion

CUSTOMER SERVICE 0900-0401351 (15 ct/min.) Or from Belgium: 0031 88 1214 012 for information about subscriptions, orders, corrections and questions. Or e-mail lezersservice@veenmedia.nl or visit newscientist. nl/faq The Netherlands Postbus 11249, 3004 EE Rotterdam attn. Veen Media, Utrecht België Postbus 102, 2910 Essen attn. Veen Media, Utrecht Prices 11 magazines a year, postage included Subscription € 92,85; youth discount € 68,50; Europe € 121,42; Outside Europe € 141,22 Single issues € 8,50 (postage not included) Subscriptions are taken out until notice of cancellation, unless otherwise specified. Editor-in-chief Jim Jansen Editors Jaap Augustinus (visual editor), Yannick Fritschy, George van Hal, Joris Janssen, Monique Kitzen (copy editor), Kristel Kleijer (coordination), Didi de Vries Phone +31-(0)88-700 2931 E-mail redactie@ newscientist.nl (press), info@newscientist.nl (queries to the editor), klantenservice@ newscientist.nl (subscriptions) Mail Postbus 13288, 3507 LG Utrecht Office Herculesplein 96, 3584 AA Utrecht ULS Martje Ebberink (coordination), Freek van Muiswinkel, Susanne van Weelden Contributors to this issue Bram Belloni, Wouter Dhert, Jan Dijksterhuis, Dick Heederik, Marleen Hoebe, Mariëtte Oosterwegel, Dorine Schenk, Maurice Timmermans, Roel Vermeulen, Sebastiaan van de Water , Bob van Toor (translation) Design Sanna Terpstra (Twin Media bv) Art direction Nancy Panjoel (Twin Media bv) Brand manager José Snel (jose.snel@ veenmedia.nl) Sales Alex Sieval (sales@veenmedia.nl) +31-(0)88-700 2661 Production manager Sonja Bon Print Habo DaCosta bv Distribution Aldipress BV (NL), AMP (B) The publisher accepts no liability for printing and typesetting errors. COPYRIGHT This Utrecht Life Sciences special is a one-time publication by VeenMedia in cooperation with Utrecht Life Sciences. All copy ©2017 Veen Media. The New Scientist logo and all its other brands are the property of Reed Business Information Ltd. No part of this publication may be reproduced, stored in a digital database or published in any form whatsoever without prior permission from the publisher. The publisher has sought the rights to the photography according to the legal regulatory provisions. Those who wish to claim certain rights, may contact the publisher.

17 Column Dick Heederik studies the risks of living in the countryside. 20 Opinion Five perspectives on the impact of science on society 22 Diary A week on the bowel cancer ward 32 Interview Nephrologist Marianne Verhaar: ‘We grow mini-kidneys from cells in patients’ urine.’

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IN FOCUS

UU

Utrecht Life Sciences Within ULS, knowledge institutes, government and businesses meet to work together. To have such a variety of disciplines within walking distance from one another is unique in the Netherlands. It makes ULS a melting pot, buzzing with ideas, that attracts young talented scientists.


Networking pioneer The task seemed impossible, when he started it twenty years ago. Yet chemist Albert Heck (52) is getting closer every day to mapping the interplay between proteins. In September, he was awarded the Spinoza Prize for his research into protein networks, and for his talent for creating great networks of scientists.

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Profile Albert Heck

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profile

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t is one of the oldest, and most exciting scientific pursuits: finding the secret of life. Over 3500 years ago, the ancient Egyptians were already dissecting dead bodies hoping to learn how organs and veins make humans tick. A little less than 350 years back, Antoni van Leeuwenhoek was able to zoom in a lot further, thanks to his invention of the microscope. He surmised that cells form the building blocks of the human body. And for about a century, we have been aware that these cells are conducted by proteins. Scientists have posed the question ever since: how do proteins manage to do that? Although the riddle is far from solved, one thing has become crystal clear: it all revolves around cooperation.

Combining is compulsory It is no coincidence that Albert Heck applied himself with passion to the mapping of protein interaction. In fact, he spends much time setting up cooperative networks himself. As professor of biomolecular mass spectrometry and proteomics at Utrecht University, he builds bridges, between chemists focusing on fundamental questions, and pharmacologists searching for new medicines. In his Utrecht University laboratory, some sixty scientists from far and wide work together on new technologies to help study the human body in ever more detail. ‘It’s such a pleasure working with Albert’, says Paul Parren, professor of molecular

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CV

Text: Yannick Fritschy Translation: Bob van Toor Photography: Bram Belloni

Albert Heck Born 1964 in Goes. 1987 teaching assistant at the National University of Lesotho 1993 PhD at Amsterdam University (UvA) 1993 Postdoc at Stanford University and Sandia National Laboratory 1996 Senior fellow and lecturer at Warwick University 1998 Professor at Utrecht University 2003 Founder and science director of the Netherlands Proteomics Centre 2010 Visiting professor of systems biology at ETH Zürich 2012 Developer of Orbitrap mass spectrometer specialised in large protein networks 2017 Recipient of NWO Spinoza Prize Albert Heck was granted a Spinoza Prize to realise his wild ideas.

immunology at Leiden University. From 2009 onward, a steady stream of studies has appeared, signed with the brotherly pair of names, Parren and Heck. ‘Albert doesn’t just know a lot about his field, he’s always willing to share that knowledge as well’, Parren says. ‘He’s extremely social

and puts his trust in others.’ Collaborations such as these are not just productive, Parren observes; today, they are part and parcel of the search for new discoveries. ‘You can’t do it alone, that’s true now more than ever’, he says. ‘On the molecular level, we have to combine diffe-


profile

rent kinds of expertise over the course of many years of research; different scientific fields as well as theoretical and practical elements.’ It is in these practical elements in particular that Heck plays a crucial part. He specialises in mass spectrometry, a technique that allows the identification of a great amount of molecules at once, distinguishing them by their mass. The method can demonstrate, for instance, which proteins are present in a given cell, as well as their form and volume. Parren: ‘Albert has access to some extraordinary technology and happily opens up his lab to new cooperations and ground breaking research.’

Understanding interactions Mass spectrometry is a technique that has been applied for decades; in fields such as forensic research, for example, where it is used to analyse physical evidence at a crime scene. In television shows like CSI: Crime Scene Investigation, it’s this method that lands many culprits behind bars, just as it does in real life. What sets Heck apart from his colleagues in this field, however, is how he uses the method to investigate mutual protein interactions rather than to identify individual proteins. In an interview with the Dutch Organisation for Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek, NWO) in June 2017 in honour of winning the Spinoza Prize, Heck elucidated the process using football as a metaphor. ‘If we want to understand why things in our bodies sometimes work well, and sometimes not so much, we have to sketch out these interactions. Compare it to a football team. When two players fall ill, the rest of the team can lag as a result, but it can also be that the players still on their feet give it their all, and win against the odds. So, understanding the interplay of proteins is at least as important as identifying which ones are present in a cell.’ But while the average footie coach oversees the actions of just eleven players, Heck deals with thousands of different proteins at any time. Twenty years ago, it was unimaginable that studying their networks would be a possibility. That didn’t deter Heck - then only 33, and already tenured at Utrecht University. Optimistically, he set

out on the seemingly impossible quest: mapping the function of each protein in the body. Trepidation, generally, is not an affliction very familiar to Heck. After finishing his bachelor’s degree at Amsterdam’s Vrije Universiteit he flew off to Lesotho for a stint as teaching assistant. As a scientist, too, he regularly ventures out into unfamiliar fields. He has studied wildly varied things, from the effect of salt water on plants to the biological clocks of bacteria. ‘Albert is a pioneer. He leads the way in his field’, says Parren. His pioneer’s spirit led him to the discovery, in 2002, of the specific way in which proteins communicate amongst each other. The technology, developed by Heck and his research group, that is able to follow this signal transduction, is currently used all over the world. Furthermore, it has allowed researchers to map hundreds of protein networks. Three years ago, Heck and Parren made another important discovery with their colleagues, which was published in the acclaimed journal Science. Parren: ‘We demon-

in point is the combination of a mass spectrometer with an electron microscope; a possibility that Förster is spending much of his time exploring. ‘Using mass spectrometry you can discern and identify a myriad of molecules. On top of that, you can analyse them in detail with an electron microscope’, he explains. ‘I rather hope that Albert might spend part of the Spinoza Prize funds on the development of a machine that combines these two techniques.’

Practically wild Heck has, so far, not revealed just how he will invest his newly acquired research endowment. In the NWO interview, he clearly states why: ‘The scientific accomplishments that I’m most proud of in hindsight, never appeared in any research proposal. Those applications require a strict realism, and therefore rarely contain the most exciting plans. I want to use this grant on those wild ideas I would never dare to put into a proposal.’ That isn’t to say such wild ideas can’t be very practical, like the development of new medicine. ‘Mass spectrometry could well

‘Albert happily opens up his lab to new cooperations and ground breaking research’ strated how antibodies activate the immune system, which may help the future development of therapies that call on the body’s own immune system, to fight cancer, for example.’ Friedrich Förster, molecular biologist at Utrecht University, also praises Heck as an innovative researcher. ‘He has a bird’s-eye view of his entire academic field, so he can spot new opportunities when they arise’, Förster says. ‘Whereas it’s much harder to set up large research alliances in The Netherlands than it is in, say, the United States, Albert often succeeds. He’s a prime organiser.’ By joining forces from different disciplines, Heck automatically ensures that a combination of methods is applied. Case

be applied to test the exact effects of a treatment’, says Förster. Apart from that, there’s a host of fundamental questions begging to be answered. Förster: ‘Before developing a new medicine you have to understand the biological mechanism behind a disease. Say you want to kill a bacterium by destroying the sugars it feeds on. First you’d have to find out which sugars to target. As such, fundamental chemistry would make up a large part of the search.’ Heck’s future research can help save lives, just as it might teach us more about how life works. Whichever direction it takes, one thing is certain: the coming years will see many more scientists crossing through his lab, working in unison to unfurl the mystery of life.

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Mini-organs on the big screen His photographs of cells made the newspapers several times before. Now, stem cell researcher Hugo Snippert has taken on a new challenge: filming mini-organs grown in petri dishes. Cancer cells have Snippert’s particular attention. His aspiration is to cast light on resistant tumors and the cause of metastasis. Text Dorine Schenk Translation Bob van Toor

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hey mostly resemble exotic corals, their fluorescence looming from the dark. The stringy, wavy shapes are brightly coloured: red, yellow, blue and green. This image, featured in a host of newspapers, was snapped by Hugo Snippert in 2010 as part of his PhD research into intestinal stem cells in mice at Utrecht’s Hubrecht Institute. His supervisor was geneticist and physician Hans Clevers. Snippert’s years in Clevers’ lab were a time of exciting discoveries. Here stood the petri dish in which the very first mini-organs were grown, for one. ‘The Clevers lab aims for great discoveries’, Snippert says. ‘The atmosphere there is extremely driven. That drive is something I try to maintain in my lab as well. I want to focus on finding new concepts, rather than keep studying small details.’

12 | New Scientist | Utrecht Life Sciences

These days, Snippert leads a research group of his own, at the Molecular Cancer Research department of University Medical Centre Utrecht. He specialises in imaging: using advanced microscopes, he captures the most extraordinary moving and still images of cells. With these, he studies the onset of diseases like cancer, as well as the interaction between tumours and varying types of medicine.

Guts on show Snippert’s current research builds on the findings of his PhD project on the intestines of mice. There, he studied the competition among stem cells – cells capable of unlimited division and able to develop into any other type of cell. Inside the murine gut, he observed intestinal stem cells transforming into epithelial cells, the kind lining the intestinal wall. These cells form the border line with the outside world. ‘The intestinal wall consists of tiny protrusions that absorb nutrients. Between them are test tube-shaped cavities called crypts’,

Snippert explains. ‘At the bottom of these crypts, you find stem cells, and rapidly dividing daughter cells along its shaft.’ As the cells divide, they push each other up, and out. After about five days they reach the top of the protrusions and fall off. This way, the entire interior lining of the intestine renews itself every five days or so. The picture that seemed to resemble corals, then, is in fact a mouse’s gut. ‘The cells inside the intestine light up, because we insert genes into them that code for the production of red, yellow, blue or green fluorescent proteins’, Snippert says. When such genes are introduced into a stem cell, it will be passed on to all of its offspring. This allowed Snippert to see exactly which cells yielded the most numerous progeny.

Headlining again The moment the first three-dimensional mini-intestine emerged from a petri dish, Snippert was there again, and ready to capture its image. ‘Toshiro Sato, a postdoc at the Hubrecht Institute at the time, succee-


Stem cells from the intestines can form an intestinal wall in the lab. ULS HUGO SNIPPERT

ded at cultivating intestinal stem cells into a mini-intestinal wall’, says Snippert. A well-trained eye can distinguish its protrusions and crypts, just as they appear in Snippert’s mouse-intestine photo. What’s more, the cells divide and migrate just as they would in an actual gut. Never before had scientists managed to grow miniorgans in a petri dish. The microscopic photos Snippert took of them, again made the newspapers. Cultivating mini-organs is not just an extraordinary feat; the resulting organic tissues have many applications too. They can be exposed to bacteria, for example, to study the reactions of healthy tissue to infections. Mini-organs can also be grown from patients’ tumors, to test tumortargeting treatments without any risk to the patient. A future application of miniorgans could be in organ transplants. Currently, when an organ fails, it is replaced wholly by a new one – with great physical repercussions for the patient. Part of the reason this method is so taxing is that the

tissue introduced often comes from another body. Snippert: ‘Often, however, only part of the organ is broken. If you could cultivate that part from a small biopsy and genetically repair it before transplanting it, the treatment might just become a lot less invasive.’

Happy medium To Snippert, mini-organs provide the ideal opportunity to film cells’ behaviour and

‘I want to find new concepts, rather than study details’ interaction. ‘The two-dimensional cancer-cell cultures that have been available for years only contain a single cell type. Those are too simple, there is no interaction between different cell types.’ They will not teach us anything about how the communication between cells and the

body as a whole works. ‘And I can’t film inside people’, Snippert remarks. 3Dmini-organs are the happy medium. They contain varying types of cells, positioned correctly in relation to each other, while still accessible enough to be studied in a laboratory. They are, in other words, the perfect way to gain understanding of how cells behave and communicate in living tissue. Snippert: ‘Ultimately, I want to film live cell biology, cells’ behaviour and development, in mini-organs grown from healthy as well as tumorous tissue.’ As a colleague of Snippert’s joked recently: ‘Clevers gave us 3D; adding the fourth dimension, time, is up to you.’ Now, Snippert’s focus is primarily on cancerous cells’ behaviour. Along with his research group he seeks to understand why tumors occasionally develop resistance to treatment, how metastasis starts and how to prevent it. When he succeeds, it will quite likely be heralded, once again, by his own photo in every newspaper.

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Printing livers for a living Utrecht University researcher Bart Spee tests medicines on printed mini-livers when he isn’t working on a new treatment for canine liver disease. Two very different branches of study, but with a common root: stem cell technology.

Text Maurice Timmermans Translation Bob van Toor

9.00 AM coffee

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he meeting room is modest, square, and situated in a building named after Jeanette Donker-Voet – the Netherlands’ first female veterinarian. Here, Bart Spee provides a preview of his research and of the professional activities ahead of him on this Wednesday. He sips his morning coffee from a mug featuring the puppy-eyed stare of an almost impossibly adorable Labrador. Actually, Spee has to admit, he is much more of a cat person, having grown up surrounded by felines. Why the mug, you ask? A gift, from a colleague with a keen sense of irony. For there’s no denying: dogs take the main stage in Spee’s work on liver stem cells. The liver is an extraordinary organ, 14 | New Scientist | Utrecht Life Sciences

the scientist says. ‘If you’d cut away 70 percent of it, the tissue would grow back completely within three weeks. In a diseased liver, however, this regenerative function gets compromised.’ A member of the Faculty of Veterinary Medicine’s expertise centre for companion animals, Spee aims to give ailing livers the boost they need to restore themselves again. He works with dogs, because they strongly resemble humans in this respect. For example, many Labradors, Dalmatians and Cocker Spaniels suffer from a liver condition that’s very similar to Wilson’s disease in humans. Here a genetic defect disrupts the body’s copper metabolism; copper particles literally build up within the liver, leading to chronic inflammations. Although treatments are available, the stem cell therapy Spee is developing is extremely promising. ‘We take stem cells out of the liver and correct the gene mutation in them. From these, we cultivate more healthy stem cells, which we re-introduce to the liver. To encourage growth, we cut

away one of the liver’s lobes. This amputation causes the new cells to immediately set to work and divide at a higher rate. The copper excess is then gradually drained by the liver’s bile.’ This treatment could have great benefits for dogs, Spee says, but ultimately his goal is to cure humans. Wilson’s disease is just one of several congenital metabolic diseases, which together form one of the top three causes of death in children. For these children, stem cell therapy could mean the difference between life and death. The arrangements with Utrecht’s Wilhelmina Children’s Hospital have already been made – although it will take another five years at least, stresses Spee, before the first young patients can undergo the treatment.

10.00 am cultivation lab The scientist’s tall frame heads the way as one door after the other automatically unlocks at a swipe of his key card – a requirement at all facilities working with genetically modified cells. A few hallways down,


His papers held in place by a plastinate of a dog’s liver, Spee works to cure Wilson’s disease (left). A bio-printer in the process of printing artificial livers out of millions of cells (below). BRAM BELLONI

BRAM BELLONI

at the cultivation laboratory, the stem cells are grown and multiplied. ‘They are taken from biopsies on dog’s livers, brought here and immediately put in a liquid cultivation medium,’ Spee says, indicating cups filled with what could be mistaken for orange soda in a cabinet behind him. ‘We add an enzyme that separates all cells, filter out the stem cells and then put them away for

The end result is the size of a Lego brick: a printed artificial liver consisting of over a cultivation. They multiply with lightning speed: after three months, we harvest 700 million cells.’ His colleague Louis Penning, research coordinator, points to a microscope showing stem cells highlighted like greasy globules. Those are mature stem cells, he ex-

plains. ‘So they haven’t been taken from embryos, they’re from the patients themselves.’ (Yes, to a vet, animals are the patients). The advantage of mature stem cells, Spee explains later, is that they are more stable. ‘If you randomly place a corrected gene back into the genome, like we do, you run the risk of activating a cancer gene. In the clinic we will use CRISPR/Cas9, the latest technique that is much safer.’

11.00 AM veterinary clinic At a stone’s throw from the Jeanette Donker-Voetbuilding, three entrances lead into the veterinary clinic, each marked by purple panels: companion animals, equine sciences and farm animal health. By walking through a waiting room full of cats in their carriers and dogs on leashes awaiting their turn we reach the treatment room; walls tiled a classic yellow surrounding the central examination table. Utrecht’s veterinary hospital receives patients from vets all over the country, when they’ve ran out of options for treatment.

Dogs are treated here for cataracts, pelvic fractures or cancer, including radiation and specialised intensive care. Not all treatments are as sophisticated, Spee says. ‘They also set canaries’ broken legs.’ Then the door swings open. In storms Aagje, a cross between a Bedlington Terrier and a Beagle. Three years of age, she was bred specifically for this study and carries the genetic defect that causes copper build-up. Tail wagging and jumping all over the place, she hardly looks the part of the lab animal wasting away. Aagje is the second dog into which cultivated stem cells have been re-introduced, says Hedwig Kruitwagen, vet and fourthyear assistant in training. Last summer, lab dog Paul was the first to receive them. It was reason for a celebration, because it was the first time researchers saw the injected cells nestled back into the liver. Spee: ‘These findings alone are interesting enough to warrant an academic publication; but to be sure, we are repeating the procedure on two other dogs this autumn.’ Utrecht Life Sciences | New Scientist | 15


report

Who is Bart Spee? Spee (Gouda, 1978) is what the Dutch call an education stacker, diligently working from the bottom up. He started vocational training (mbo-level) to become a lab worker, progressed to professional training (hbo) before being ‘discovered’ by veterinary medicine professor Jan Rothuizen during an internship at his faculty. The professor encouraged Spee to pursue a PhD, and so it happened – in 2006, Spee attained his doctorate with flying colours with a thesis on canine liver diseases. Excursions to Leuven University and the United States followed, after which Spee returned to his alma mater in 2010, in the role of assistant professor. There, he studies stem cells to treat liver disease in humans and animals, and to investigate new medicines.

Cultivated stem cells were introduced back into the liver of Aagje the dog. BRAM BELLONI

14.00 PM work meeting Spee and Kruitwagen convene with a surgeon to discuss the best time for the two stem cell transplants. The recipients of the operations will be Dasher and Aron (all dogs are named by their caretakers). In Aagje, corrected stem cells were replaced via the so-called portal vein, a blood vessel leading from the intestines to the liver. Dasher and Aron will receive their cells both through that same vessel as well as directly into the liver. ‘The latter scenario allows for fewer cells to be injected at once,’ Spee later explains, ‘but they do seem to adhere much better. Eventually one of the routes will turn out to be the better option.’

mage. Even though medicines go through trials on test animals, those trials only have a predictive value of 70 percent. We can do better than that, Spee thought. Last summer, he was granted 650.000 euros to design an alternative testing method, in cooperation with the Hubrecht Institute and UMC Utrecht. Their

Many Labradors, Dalmatians and cocker spaniels suffer from a liver condition similar to Wilson’s disease

15.00 PM bio-printer Around the block is the Hubrecht Institute, where Hans Clevers set up his revolutionary stem cell study. Entering the lift, Spee presses 4; the floor on which he has his artificial mini-livers readily printed out. Naturally, stem cell research serves multiple purposes, and could also make a big difference to the testing of new medicines. There’s a lot to gain in that area: 10 percent of all medicines, some already commercially available, turn out to be toxic. They cause unexpected side-effects, such as liver da16 | New Scientist | Utrecht Life Sciences

plan: to create an artificial version of the human liver to be used in medicine trials. This is called bio-fabrication. But how to make an imitation of a liver? Taking liver cells from the body has little purpose indeed, for the cells collapse within a matter of hours. A more fruitful approach is cultivating stem cells into mature liver cells. But that’s easier said than done, says Spee, since it requires researchers to create a micro-environment that closely resembles their natural surroun-

dings, proteins like lamins and collagen, to name just a few. After giving a short tour of its antiquated siblings, lab worker Mattie van Rijen has installed himself before a state-of-the-art bio-printer. Van Rijen demonstrates how cells and their micro-environment, encased in gel, can be printed from a cartridge. The machine begins to buzz. Meanwhile, Spee has picked up an example of the end result, the size of a piece of Lego: a previously printed artificial liver, consisting of over a million cells. Over the next months, many more will emerge from the printer. They will then be wired together into a fully-fledged bio-reactor by biotechnology company LifeTec Group. New medicines can then be dissolved in liquid and subsequently conducted through the liver tissue. This method of testing comes with another important benefit, Spee says. ‘Lab animals would no longer be needed.’

16.00 PM wrapping up Back in his own office, Spee walks up to his desk. He reaches for a pile of what appear to be hastily stacked flounders. Look, he says, lifting the entire fishy pile at once: ‘There you go: a plastinate dog’s liver. Isn’t it humongous?’


opinion column

Rural risks Cities are polluted, while countryside dwellers get to breathe in wholesome farmland air. That sounds more idyllic than it is in practice, though – those who live near livestock farms expose themselves to other risks.

I

n the Netherlands, we live in close proximity to intensive stock farms, yet we’re not always aware of the risks that entails. Think of the notorious antibiotic resistant hospital bug MRSA, that reared its head on pig farms in 2005. Now, these bacteria are found on many pig and cattle farms, creating risks for neighbouring residents. Between 2007 and 2009, Q fever, caused by the germ Coxiella burnetii, devestated goat farms. In goats, the bacteria caused premature births and storms of abortions. An undesirable situation for the animals, yet the consequences turned out even more dramatic when the bug jumped to humans. Coxiella burnetii infected over 4500 people, of whom an estimated 30 died. Incidents like these are tragic, but shouldn’t come as a surprise. In our tightly-packed country, there is much opportunity for contact between humans and animals. Airborne microbes, for instance, are very easily transferred from livestock to people living in the vicinity. If we want to more accurately map out the risks stock farms pose to those living near them, however, we will have to do more research on the issue. That is why some colleages and I started the extensive ‘Livestock and Resident Health’ (Veehouderij Gezondheid Omwonenden, or VGO) project. We gauged the risk of infection with antibiotic resistant micro-organisms for residents in the vicinity and the risk of animalrelated disease transferral. We also looked at the effects of stock farms’ potentially dangerous particulates emissions on residents’ respiratory systems. Because these questions are very different, our research involved intensive

cooperation with experts from several institutions, such as Utrecht University, the National Institute for Public Health and the Environment, Wageningen University and health research institute NIVEL in Utrecht. Thus, we got to work with environmental experts able to measure air pollution and microbiologists who analysed cattle-related bugs and toxins. Epidemiologists subjected GP’s medical files to thorough data-analyses, to reveal if the cases of contagious or respitory disease in those files corresponded to activity on nearby farms. The success of this interdisciplinary approach was apparent from the large number of publications in esteemed journals that the research project spawned. More importantly though, the VGO

The Q fever bacteria took about 30 human lives

study forms the first step towards answering the questions and concerns residents may have about their health. Individuals living near poultry and goat farms, for example, are more likely to develop pneumonia – on average, the area that was studied counted 119 extra patients per 100,000 people, an increase of 7.2 percent. Another analysis showed that COPD patients close to stock farms suffered worse symptoms than those living farther away. This is presumably caused by particulate matter, though we didn’t eliminate the possibility that germs from animals contribute to this increase as well. Findings like these are not just of academic value; they have an impact on society as well. Later this year, the Dutch Health Council will present a new directive on health risks associated with livestock farming. This wouldn’t have been possible if it weren’t for the scientific foundations laid by research such as the VGO study.

Dick Heederik is professor of health risk analysis at the Institute for Risk Assessment Sciences, Utrecht University. Ed van Rijswijk

Utrecht Life Sciences | New Scientist | 17


Colourful guts Proteins are a cell’s means of communication. When one cell emits a protein, a neighbouring cell picks it up – causing a chain of reactions within it. Text Kristel Kleijer

R

eaction chains are a vitally important part of embryonic development. They ensure, among other things, that each body part, each organ, indeed each cell ends up in place. Should the regulation of a chain go awry at a later stage in life, this regularly results in tumors. Professor Madelon Maurice cultivates cells and stem cells in UMC Utrecht to study reaction chains. In a laboratory setting, stem cells from the intestines can be grown into three-dimensional miniintestines. This allows for the contributing reaction chains to be meticulously followed and studied during this process.

These colourful cells were grown in a laboratory. Under the microscope they light up with fluorescence. The red, green and blue colours are attached to different proteins in the cell, distinctly showing their placements. 18 | New Scientist | Utrecht Life Sciences


The cultivation lab also grows three-dimensional mini-intestines. The cells are neatly arranged within the organ’s tissue.


opinion comment

‘High-quality science changes society’ No scientist would argue against the notion, that science of high quality can change society. Five of Utrecht Life Sciences’ finest scientists reflect on why our society can’t go without top-tier science.

Text Didi de Vries Translation Bob van Toor

Marc Bonten, professor of Medical Microbiology, UMC Utrecht

‘Almost everything we use originated from scientific research: cars, navigation systems, telephones. Knowledge is indispensable to our world. How much of an impact research has, varies per subject. A new development in cancer treatment, for example, will make more waves than a study of the medieval jackdaw. Not to discredit the latter field, but it has less of a direct influence. There is, alas, also such a thing as low-quality science. Anyone can access a slew of publications, as the number of scientific journals and popular science magazines has grown exponentially over the last decades. Everything that has anything to do with science, ends up getting published. That makes it difficult to separate the wheat from the chaff sometimes. Research of 20 | New Scientist | Utrecht Life Sciences

questionable quality, along with its dubitable conclusions, trickles into journals – making the assumption that everything printed there is true a shaky one indeed. And this data diarrhea makes it especially hard for the uninitiated to judge the value of each new study. With time and more research, though, each statement that is false but has been presented as true will inevitably be exposed. High-quality science will triumph in the end – but sometimes it may take a while.’ Genoveva Keustermans, PhD-student, UMC Utrecht

‘Science is in service to society, and therefore should bring forth improvements. That focus can lift science to a higher level. To me, science of high quality is understandable to society, verifiable, unbiased and reproducible. Reproducible, that is, not just in your own laboratory, but anywhere else too. Low-quality science exists as well, although I’m convin-

ced that every scientist is dedicated to attaining the highest quality possible. Unfortunately, some stray from that ideal under the pressure to publish, to keep the institute that finance them happy, yielding research that lacks quality. Other financing mechanisms could break that pattern. Change brought along by scientific research is always a good thing, I feel. Of course, the development of the atomic bomb was anything but positive, but its preparatory research has taught us a lot about radioactivity and nuclear energy. I think it’s vital not to hide what you’re working on, but to show the world whatever you’re researching. Ultimately, science will improve life for humans, plants and animals.’ Wioleta Marut, immunologist, Utrecht University and UMC Utrecht

‘I agree with the notion, yet it depends on how one defines high quality. A requisite would be that research is accessible

to a broad population, as well as understandable. I see many scientists get that wrong. Some don’t take that last step in translating their work, others fall prey to media cherrypicking a catchy one-liner and drawing their own conclusions from that. The latter is often done with highly esteemed journals like Nature and Science. Less celebrated journals are often ignored, even though they publish research just as noteworthy. Still, many scholars feel this regrettable pressure to publish, since it may mean higher approval from peers and possible research grants. That doesn’t always benefit scientific quality, as there might be less time for thorough research, combing through potential side effects and reproducing results in another setting. Change is not always a good thing, and the media are partly to blame for that. There are countless examples in food science alone. The idea that eating gluten is unhealthy, to name one; or that we should fry our food in coconut oil as much as possible. They grow into trends, while research clearly demonstrates that gluten is only bad for the health of


very few people and there’s absolutely nothing wrong with sunflower oil. Wrong interpretations of research results could even turn out to be dangerous, as became clear when one study suggested a link between vaccinations and autism in children. The research was never reproduced. Only a single article was published on it, and subsequently retracted after a storm of criticism. Nevertheless, many people firmly believe that vaccines are a health risk to this day.’ Roos Masereeuw, professor of Experimental Pharmacology, Utrecht University

‘Scientific research certainly influences our lives. Often, however, a fundamental discovery has to go through many stadia before it can have its true impact in everyday life. Take the bioengineered kidney, for example. After working on it for eight years, we can now create a functional kidney tube in the lab; but it still has to go through pre-clinical trials. It’ll be a few years, therefore, before we can place an actual artificial kidney in a patient’s body. Change like that is gradual, but that doesn’t make the knowledge gained along the way any less valuable.

The fear for negative side-effects to vaccination defies all scientific thought. FRANK DE ROO - FOTOBUREAU DE ROO/HOLLANDSE HOOGTE

The image gets distorted when the media jump on research that is foundational and still in its early stages, yet to be checked and proven but subject to high expectations. Researchers’ enthusiasm is prized more highly in those situations than results – since

Roel Vermeulen, professor of Environmental Epidemiology, Utrecht University

‘Quality research often plays out on the cutting edge between different disciplines. Its most vital component is systematically acquired knowledge, obtained by scientists through

‘Wrong interpretations of research results can be dangerous' they haven’t arrived yet. Development in general is a positive matter, but it depends on the criteria the development is judged by. A car allows for rapid transport, for example, but is detrimental to the environment. So is it a positive or a negative? Likewise, technology like CRISPR/Cas9 can help us prevent congenital disorders, but won’t that also lead to parents wishing for superbabies?’

the use of theories, methods and technology. In modern society there’s a growing demand for social impact in addition to scientific impact. A good example of this is the recently presented National Science Agenda (Nationale Wetenschapsagenda or NWA), in which the national hunger for knowledge has been charted after extensive consultation of citizens’ questions. It contains questions such as how can we stay strong and

healthy as we age? The NWA’s adage sapere audere, dare to ask, clearly rings true for society at large just as much as for academia! Change doesn’t always have to be positive. The past contains plenty of examples of scientific knowledge being used to society’s disadvantage. Einstein could not have fully fathomed his E=mc2 would be applied in the development of the nuclear bomb. In the current age, scientists cannot and should not assume that their knowledge will only ever be used to serve the public good. Society, in turn, increasingly casts doubts on science. Denial of climate change and fear for vaccinations defy all scientific thought. These are worrying developments. More than ever, scientists have to stay rooted firmly in society, and institutes must safeguard the quality and integrity of scientific research and education.’ Utrecht Life Sciences | New Scientist | 21


diary

A week in the life of internist-oncologist Miriam Koopman Patient care, quantitative research, boot camps and two young kids: professor Miriam Koopman (42) juggles it all with skill. The UMC Utrecht internist-oncologist tries to keep all parts of her life from spilling into one another, but isn’t always able to. Hence, she can regularly be found on the phone with a patient during her scheduled research day or answering urgent e-mails on her Wednesday off. Text Dorine Schenk Translation Bob van Toor

22 | New Scientist | Utrecht Life Sciences

MON

It’s the first working day after the summer holidays, and already I’m running fifteen minutes late. The entire campus appears to be broken up; I found my route blocked by a large barrier. Construction work on a tram line between the train station and the hospital led me on a bit of a detour. The lenient starting time at the ‘academic quarter’ after the hour does not exist in the hospital. I’m taking over from the oncologist who was on duty over the weekend, and only make it just in time for the handover. My colleague brings me up to date on the matters of the past days in the department. No big surprises, fortunately. Now that I’m back, it’s time for my close colleague to take a holiday break. After I’ve been put in charge, I hurry towards the esophageal cancer outpatients’ ward, or policlinic, where I’m replacing her this morning. At noon, all oncologists and oncologists in training gather for policlinical meeting. Here, all new patients’ files and their problems are presented to all the staff. Together, we discuss new treatment plans for new arrivals. We check if everyone agrees with the chosen strate-

gies, or whether there remain any doubts. Meanwhile, we have our sandwiches. I seldomly lunch alone, since there’s always something to discuss. In the afternoon, an oncologist in training interns at the clinic; I supervise his internship, focused on bowel cancer. UMC Utrecht, after all, is an educational institution with many medical students and specialists in training. The spare moments, I use to prepare my own consultations, tomorrow.

TUE

At eight-thirty in the morning I join a video conference. A radiologist, surgeon and a medical oncologist at the UMC are convening with doctors at the St. Antonius Hospital elsewhere in Utrecht. Collaborations such as these are crucial to provide the best possible care. We discuss new patients that were recently diagnosed, go over patients’ problems and how to handle them. The rest of the morning I spend seeing outpatients at the clinic. Since about one year, the UMC has switched to a tumor-focused strategy. Patients with similar tumors are sent to the same policlinic and the same expert in that particular field – in this case,

the colorectal cancer clinic. For patients with other types of tumors, there are other specialised policlinics, like the esophageal cancer clinic, where I took yesterday’s shift. At the colorectal cancer clinic, about 90 percent of patients have tumors in their bowels; the other 10 percent are patients that I had been treating before the switch to a tumor-focused approach was enacted. We did not ask them to switch doctors. This time, I have lunch with colleagues from the Regional Academic Cancer Centre Utrecht (RAKU). Together, we set up treatment plans for patients with tumors in the stomach, liver, pancreas, esophagus and gall bladder. The rest of the afternoon is spent on patients coming in for check-ups. I have a couple of phone calls to make, letters to write and CT scans to request. The hours fly and although the work is far from done, I leave for home at six. Tonight I have fitness boot camp, so eating beforehand is essential.

WED

On Wednesdays, I’m free from work. With two kids aged five and seven, I think it’s impor-


1,0

Colorectal cancer is one of the most prevalent diseases in the Netherlands. In 2016, 1 in 1000 men and 0,8 in 1000 women were diagnosed with bowel cancer.

At UMC Utrecht, oncologists follow a tumorfocused strategy. Of all of Miriam Koopman’s patients, 90% suffer from bowel cancer. THINKSTOCK

tant to dedicate this day to them. Still, once they’ve left for school, inevitably the computer comes on. I’m due to speak at a congress soon, and still have to prepare my presentation. Today is an excellent opportunity for it.

THU

The week’s second half, I focus on scientific research. This morning I take the bike to the Netherlands Comprehensive Cancer Organisation (IKNL) to discuss a research project. In this project, we collect data on as many bowel cancer patients as possible. At this moment there are as much as fifteen sub-studies being done on over two thousand patients. We want to use all the information gathered to gain insights in the effectiveness of treatments as well as their in-

fluence on patients’ quality of life. March is the international colorectal cancer month, and we’re hard at work preparing for it. To have such a month may sound strange, but bowel cancer should get much more attention. It is one of the most prevalent diseases in the Netherlands, yet almost no one is aware of it. With a themed month, we want to reach hospitals and their patients, in order to have more people participate in the bowel cancer research. Care and research aren’t two separate concepts: it is precisely when the two converge, that we can significantly improve treatment and quality of life. The day ends on a festive note: a PhD student’s article has been approved for publication. An excellent reason for ice cream!

FRI

My Friday kicks off at the desk of Onno Kranenbug, professor of translational tumor biology at UMC Utrecht. We cooperate on several research projects. While interested in the same subjects, we approach them from different perspectives, which is immensely helpful to the research. Afterwards, I have a meeting with a PhD student to go over her research progress. Karlijn van Rooijen is working to find out which patients would benefit from additional chemo therapy, after their tumors have gone. Recently, scientists have shown that certain patients, while they seem to be cured, still have tiny fragments of tumor afloat in their blood. These patients, regrettably, frequently relapse. Karlijn is stu-

dying whether extra treatment is an effective way to keep the disease from flaring up again. I discuss my other PhD students’ progress with them as well. After lunch, I teach a class for oncologists in training. As the afternoon draws to a close, I make a round of my patients in the ward. I like to have paid them all a visit, before the weekend sets in.

SAT/SUN

On weekends, I spend a lot of time outside. After a week of being cooped up, I love to take long walks. Sunday is all about sports. I start the day with boot camp and in the afternoon it is the kids’ turn: one goes swimming, the other’s off to play hockey. We are more than happy to shuttle them there and back again.

Utrecht Life Sciences | New Scientist | 23


What they do These scientists don’t shrink back from the big questions. All four have one final goal: to know exactly how things work. Text Marleen Hoebe Translation Bob van Toor

Nina van Sorge (1976) Microbiologist, UMC Utrecht

Bacteria in a different coat Our bodies are rife with bacteria, and there’s nothing wrong with that. Some of them, however, pose a risk to our health as they can cause infection. Our immune system recognises unwanted guests by their coats: the sugar structures surrounding bacteria. Nina van Sorge studies the way these microbes create their coatings, and how bacteria literally ‘sugar-coat’ themselves. Bacteria like to fool us. A small change in the sugar structure can lead our bodies, even vaccinated bodies, to miss the signs of danger. Antibiotics, too, target bugs’ sugar coats. So a bacterium that changes its spots, could well develop resistance. Take Staphylococcus aureus, which has developed into a multi-resistant bacterium. 24 | New Scientist | Utrecht Life Sciences

Most of us are hosting to Staphylococcus aureus on our skin and in our noses, with no trouble. It can cause infection, however, when the skin or the mucous membrane is damaged. That is what happens with MRSA bacteria, Staphylococcus aureus’s multiresistant variant. Antibiotics are powerless against it, making the infection very dangerous for patients with impaired immune systems. Van Sorge’s research may well give antibiotics and vaccines their grip back on these bugs.

Nina van Sorge studies bacterial ‘sugar coatings’.

Cell upside down

cells all positioned in the right order: top side up. For that is the one side that can absorb nutrients from the digested food passing through the gut. The underside of these cells, on the other hand, secretes these nutrients to deliver them into bloodstream. What would happen if these cells were upside down? Mike Boxem studies cell polarity. He observed a loss of polarity in many cancer cells, for instance. Boxem intends to apply his research grant to finding out what that loss does to a cell. As a coordinator of a European research network, Boxem organises international conferences on the subject. Here, scientists find a platform to share their results, compare and combine their findings to quickly reach breakthrough discoveries.

The body’s cells aren’t tiny, randomly dispersed bits of human tissue; they are highly specialised and carefully located. They have a top, a bottom, sides and a middle. This so-called cell polarity is crucial – in the embryonic stage especially, but later on as well. The intestines, for example, are lined with

What would happen if intestinal cells were upside down?

Mike Boxem (1974) Developmental biologist, Utrecht University


In his study of cell polarity, Mike Boxem is putting the world of cells upside down – literally.

Marvin Tanenbaum peeks into living cells to see how they produce proteins, using a technique of his own design.

Marvin Tanenbaum (1980) Cell biologist, Hubrecht Institute (KNAW)

A peek into cells Our body’s functioning is no simple matter, even though it seems like that at times. It requires complex biological processes that baffle even the most experienced cell biologists. To take a close look at the very fabric of our bodies, Marvin Tanenbaum has developed a special method: SunTag Translation Imaging. Since its conception, this unique tool has contributed to several international publications.

The body is made up of cells, and to function properly, these cells need proteins. The ideal makeup for these proteins is recorded on the DNA. They are produced via socalled messenger RNA (mRNA). Disrupted protein production can lead to a variety of diseases, from cancer to neurological conditions. When this is the case, cells produce too much or too little protein, sometimes even in the wrong places. The inner workings of protein production are the focus of Tanenbaum’s research group. Using his own technique, Tanenbaum is able to follow how a single mRNA molecule is translated to proteins within living cells. He wants to discover how cells know how to make protein in the right amounts and thus behave in the way they’re supposed to in the body. To be able to comprehend this immensely complex biological process, much knowledge is needed of molecular processes and cell biology. Tanenbaum therefore counts his blessings to be working amid all the specialists at Utrecht Life Sciences.

Saskia Braber (1981) Pharmacologist, Utrecht University

Prebiotics for intestines Calves’, mice’s and infants’ guts: Saskia Braber is interested in all of them. When the intestine is damaged, its defences against detrimental outside forces drop. Nutrition

Saskia Braber works to keep the gut as well as the lungs healthy, using sugars.

contributes to this significantly. Cereal grains, for instance, can carry fungi that produce poisonous substances called mycotoxins. These toxins can even interfere with an unborn child’s intestinal barrier via the food its mother eats. But Braber knows that it is in food, too, that solutions may be found. That’s why it’s not just universities, but also companies like baby food producer Nutricia that follow her research with a keen eye. In drink form, indigestible nutrients called prebiotics can help maintain intestinal health. Among these prebiotics are oligosaccharides, compound sugars that form the main subject of Braber’s research. It has already been established they have a beneficial effect on babies’ and young animals’ immune systems. Braber wants to find out if oligosaccharides can also restore impaired intestinal membranes in mouse, calf and human cells. A few floors up from the gut, Braber also noticed oligosaccharides’ beneficial impact on the lungs. How exactly the nutrients end up in the respiratory system to provide their aid up there thus far remains a mystery. But that has never daunted Braber. Utrecht Life Sciences | New Scientist | 25


Profile Alexander van Oudenaarden

Stem cell among scientists Biologist or physicist? Superstar or shy colleague? Researcher or director? Is he Dutch or American, data geek or rock musician? Alexander van Oudenaarden (47), winner of the 2017 Spinoza Prize, is not easily pigeonholed. Who is he really, and what could account for his success? His fellow scientists offer a few suggestions.

BRAM BELLONI

26 | New Scientist | Utrecht Life Sciences

Utrecht Life Sciences | New Scientist | 27


Profile Alexander van Oudenaarden

Stem cell among scientists Biologist or physicist? Superstar or shy colleague? Researcher or director? Is he Dutch or American, data geek or rock musician? Alexander van Oudenaarden (47), winner of the 2017 Spinoza Prize, is not easily pigeonholed. Who is he really, and what could account for his success? His fellow scientists offer a few suggestions.

BRAM BELLONI

26 | New Scientist | Utrecht Life Sciences

Utrecht Life Sciences | New Scientist | 27


Text: Sebastiaan van de Water Translation: Bob van Toor

T

he scene could have been taken straight from a movie script. An unexpected late night call. An unfamiliar voice extending congratulations out of the blue. A curious spouse straining to catch a word or two from the couch, followed by a grin that slowly lights up the face of our protagonist. The only thing missing would be a shouted ‘cut!’ from a director. That was a few months ago. ‘The toughest part was keeping mum’, says Anna van Oudenaarden, Alexanders Russian-born wife and colleague. ‘For weeks, we couldn’t tell anyone about that phone call.’ When the news finally broke, it raced through every last corridor and laboratory at Utrecht’s Hubrecht Institute, instantly reaching the ears of its two hundred-odd biologists as they grappled with the mysteries of stem cells. Their director Alexander van Oudenaarden, the man whose CV was already too hefty to staple together, had been awarded the single most prestigious science grant in The Netherlands; the NWO Spinoza Prize. His predecessor had predicted as much at Van Oudenaarden’s appointment in 2012: ‘We’ve landed a superstar.’

Superstar or shy colleague? Say, you’ve been assured your entire life by those around you that you are extremely 28 | New Scientist | Utrecht Life Sciences

smart. You get a degree, a PhD, do research and, to your delight, make it to professorship. But then, suddenly another researcher comes to work at the lab. Someone who, never blinking an eye, comes up with solutions to the complex conundrums you have tried to tackle for ages. A person constantly showered with praise, prizes and promotions. If a journalist ever finds their way to your desk – all you’re asked is questions about this ‘superstar’. Surely, some envy would only be natural? Not if said superstar is Alexander van Oudenaarden. ‘I recall the first time I saw him’, says Jacco van Rheenen, professor of intravital microscopy at Utrecht University and UMC Utrecht, as well as group leader at the Hubrecht Institute. ‘There he was, attentively poring over his microscope. That must have been around 2008, when he took a sabbatical at the Hubrecht Institute. I got to know him as an amicable, enthusiastic scientist. I didn’t have a clue then that he already was quite the big shot in America, leading a top team at MIT. He never bragged about those things. He is outstanding, but a little shy as well. That’s why no one begrudges him anything.’ It was already clear even back then, that

Utrecht University professor of developmental biology Sander van den Heuvel. ‘As elsewhere, enormous amounts of data are generated within the field of biology today. Many biologists are unsure how to handle that. Maths, to them, is a foreign land.’ Where many biologists falter, Van Oudenaarden goes the distance. Using techniques of his own design he plunges into the individual cell, hoping to piece together exactly what goes on inside. Why is it that a stem cell becomes a spermatozoid, not a hair cell? ‘His razor-sharp insights were of great help to us all’, Korswagen recalls. ‘Yet I never thought we would see him return here after his sabbatical. Why would he? Didn’t he have a dream job in America?’ Anna van Oudenaarden has the answer. ‘That sabbatical was an excuse. He wanted his children to grow up in the Netherlands. It was for that reason he decided to try working in the Netherlands – something he had never done.’ It became official in 2012: the superstar would return to the Hubrecht Institute, as director. ‘That did raise a few murmurs’, Van Rheenen remembers. ‘Great guy, and a fine scientist; but did he have the experience and authority for the position?’

‘I didn’t have a clue, then, that he already was quite the big shot in America’ Van Oudenaarden takes a different approach to science than from the rest of the Institute. ‘We’re all biologists here’, says Rik Korswagen, professor of molecular developmental genetics. ‘At MIT, Van Oudenaarden was professor of biology as well as professor of physics. He even holds a PhD on solid state physics – you really can’t get much closer to the ultimate in physics. That gives him a unique perspective in his work.’

Biologist or physicist? In the world of science, where experts from one field wouldn’t understand the first thing about studies in another field, Van Oudenaarden’s polymathy is crucial, says

Researcher or director? Van Oudenaarden was not without doubts himself. After all, he was a scientist through and through. A man driven by the urge to discover why things are the way they are. Though not religious, given the eternal life he would certainly spend the first millennium on the celestial plane – well, probably playing guitar. ‘But in second place, he’d definitely choose performing hard dataanalyses. He sincerely enjoys it’, his wife Anna knows. As director, Van Oudenaarden was dealt a different hand of tasks. Meetings, logistical problem-solving, firing employees, acquiring funds, appeasing politicians and journalists alike. ‘That last area was a forte

CV

profile

Alexander van Oudenaarden

Born 1970 in Zuidland (South Holland, the Netherlands) 1998 PhD applied physics (cum laude) at TU Delft 1998 Postdoc at Stanford University 2000 Transfer to MIT, Boston 2004 Associate professor, MIT 2008 Professor of Physics, MIT 2009 Professor of Biology, MIT 2012 Research director at Hubrecht Institute (KNAW) 2012 NWO VICI grant 2013 Professor of Quantitative Biology of Gene Regulation, UU/UMC Utrecht 2017 NWO Spinoza Prize Second to playing the guitar, Van Oudenaarden’s favourite activity is analysing data.

of his predecessors Ronald Plasterk and Hans Clevers. Knowing that was part of his trepidation. Multi-talented as her husband might be, he never was the type to take the stage and showcase a set of opinions to his audience. Still, he did not shy away from the challenges of the director’s office. A decade at MIT had turned him into enough of an American to embrace their typical can-do attitude.

Dutchman or American? He met his wife in the United States, his three kids were born there and with his

rock band Asymptonic Freedom Van Oudenaarden let it all hang loose on stage. ‘And yet, Alexander hasn’t been completely Americanised’, according to Van den Heuvel. ‘He doesn’t expect his co-workers to be at work eleven hours a day. He himself isn’t either. We live in the same town, and I often see him taking his kids to school, by bike.’ ‘He’s not trying to turn the Hubrecht Institute into an MIT clone’, says Van Rheenen. ‘The main difference? At MIT, research groups are forever trying to one-up one another. Everyone is in competition. The Hubrecht Institute is also performan-

ce-oriented, but Van Oudenaarden likes his institute with its specific Dutch flavour. For example, as soon as he was appointed the new director opened every door to his own research group. He started talks with scientists from other teams and came up with new ways in which they could assist one another. Co-operation became the magic word. ‘There are so many examples’, Van Rheenen recounts. ‘Recently, my group used highly sophisticated cameras to record how stem cells in mice adapt into mammary gland cells. Subsequently, Van Oudenaarden dived into individual cells, using his technology to collect more precise data on RNA expression. Both methods are unique, yielding insights on the way cells are supposed to function. That, in turn, allows us to better determine which kind of glitch could theoretically lead to cancer’, explains Van Rheenen. Since then, cooperation has become ingrained in the Institute’s culture; collaborations are even forged across the coffee table between PhD candidates. ‘Everyone realises that elbowing one’s way to the front is not necessarily appreciated.’ Van Rheenen concludes. Colleagues are unanimous in their verdict: as director, Van Oudenaarden has continued to excel. Korswagen: ‘Filling Clevers’ shoes was no easy task, but he succeeded, on his own terms.’

Single-cell or multicellular? In the archipelago of science, full of isolated isles of research, Van Oudenaarden has emerged as its ideal physicist-biologist, researching-directing, rocking, geeky, Dutch-American competitive teamoriented builder of bridges. In the evolution of life, the transition from single-cell to multicellular life was a crucial stage. Suddenly individual cells were no longer fated to fight amongst themselves, but could strive towards higher goals, each through their own specialisation. That is exactly how Van Oudenaarden envisions the Hubrecht Institute. Individual research cells should not compete, but rather strengthen each other like cells of a multicellular life form, working towards a transcendent objective: to accrue knowledge. As Spinoza wrote: the aim should be to be to find that which is unlimited and eternal, and can be owned by all. Utrecht Life Sciences | New Scientist | 29


Text: Sebastiaan van de Water Translation: Bob van Toor

T

he scene could have been taken straight from a movie script. An unexpected late night call. An unfamiliar voice extending congratulations out of the blue. A curious spouse straining to catch a word or two from the couch, followed by a grin that slowly lights up the face of our protagonist. The only thing missing would be a shouted ‘cut!’ from a director. That was a few months ago. ‘The toughest part was keeping mum’, says Anna van Oudenaarden, Alexanders Russian-born wife and colleague. ‘For weeks, we couldn’t tell anyone about that phone call.’ When the news finally broke, it raced through every last corridor and laboratory at Utrecht’s Hubrecht Institute, instantly reaching the ears of its two hundred-odd biologists as they grappled with the mysteries of stem cells. Their director Alexander van Oudenaarden, the man whose CV was already too hefty to staple together, had been awarded the single most prestigious science grant in The Netherlands; the NWO Spinoza Prize. His predecessor had predicted as much at Van Oudenaarden’s appointment in 2012: ‘We’ve landed a superstar.’

Superstar or shy colleague? Say, you’ve been assured your entire life by those around you that you are extremely 28 | New Scientist | Utrecht Life Sciences

smart. You get a degree, a PhD, do research and, to your delight, make it to professorship. But then, suddenly another researcher comes to work at the lab. Someone who, never blinking an eye, comes up with solutions to the complex conundrums you have tried to tackle for ages. A person constantly showered with praise, prizes and promotions. If a journalist ever finds their way to your desk – all you’re asked is questions about this ‘superstar’. Surely, some envy would only be natural? Not if said superstar is Alexander van Oudenaarden. ‘I recall the first time I saw him’, says Jacco van Rheenen, professor of intravital microscopy at Utrecht University and UMC Utrecht, as well as group leader at the Hubrecht Institute. ‘There he was, attentively poring over his microscope. That must have been around 2008, when he took a sabbatical at the Hubrecht Institute. I got to know him as an amicable, enthusiastic scientist. I didn’t have a clue then that he already was quite the big shot in America, leading a top team at MIT. He never bragged about those things. He is outstanding, but a little shy as well. That’s why no one begrudges him anything.’ It was already clear even back then, that

Utrecht University professor of developmental biology Sander van den Heuvel. ‘As elsewhere, enormous amounts of data are generated within the field of biology today. Many biologists are unsure how to handle that. Maths, to them, is a foreign land.’ Where many biologists falter, Van Oudenaarden goes the distance. Using techniques of his own design he plunges into the individual cell, hoping to piece together exactly what goes on inside. Why is it that a stem cell becomes a spermatozoid, not a hair cell? ‘His razor-sharp insights were of great help to us all’, Korswagen recalls. ‘Yet I never thought we would see him return here after his sabbatical. Why would he? Didn’t he have a dream job in America?’ Anna van Oudenaarden has the answer. ‘That sabbatical was an excuse. He wanted his children to grow up in the Netherlands. It was for that reason he decided to try working in the Netherlands – something he had never done.’ It became official in 2012: the superstar would return to the Hubrecht Institute, as director. ‘That did raise a few murmurs’, Van Rheenen remembers. ‘Great guy, and a fine scientist; but did he have the experience and authority for the position?’

‘I didn’t have a clue, then, that he already was quite the big shot in America’ Van Oudenaarden takes a different approach to science than from the rest of the Institute. ‘We’re all biologists here’, says Rik Korswagen, professor of molecular developmental genetics. ‘At MIT, Van Oudenaarden was professor of biology as well as professor of physics. He even holds a PhD on solid state physics – you really can’t get much closer to the ultimate in physics. That gives him a unique perspective in his work.’

Biologist or physicist? In the world of science, where experts from one field wouldn’t understand the first thing about studies in another field, Van Oudenaarden’s polymathy is crucial, says

Researcher or director? Van Oudenaarden was not without doubts himself. After all, he was a scientist through and through. A man driven by the urge to discover why things are the way they are. Though not religious, given the eternal life he would certainly spend the first millennium on the celestial plane – well, probably playing guitar. ‘But in second place, he’d definitely choose performing hard dataanalyses. He sincerely enjoys it’, his wife Anna knows. As director, Van Oudenaarden was dealt a different hand of tasks. Meetings, logistical problem-solving, firing employees, acquiring funds, appeasing politicians and journalists alike. ‘That last area was a forte

CV

profile

Alexander van Oudenaarden

Born 1970 in Zuidland (South Holland, the Netherlands) 1998 PhD applied physics (cum laude) at TU Delft 1998 Postdoc at Stanford University 2000 Transfer to MIT, Boston 2004 Associate professor, MIT 2008 Professor of Physics, MIT 2009 Professor of Biology, MIT 2012 Research director at Hubrecht Institute (KNAW) 2012 NWO VICI grant 2013 Professor of Quantitative Biology of Gene Regulation, UU/UMC Utrecht 2017 NWO Spinoza Prize Second to playing the guitar, Van Oudenaarden’s favourite activity is analysing data.

of his predecessors Ronald Plasterk and Hans Clevers. Knowing that was part of his trepidation. Multi-talented as her husband might be, he never was the type to take the stage and showcase a set of opinions to his audience. Still, he did not shy away from the challenges of the director’s office. A decade at MIT had turned him into enough of an American to embrace their typical can-do attitude.

Dutchman or American? He met his wife in the United States, his three kids were born there and with his

rock band Asymptonic Freedom Van Oudenaarden let it all hang loose on stage. ‘And yet, Alexander hasn’t been completely Americanised’, according to Van den Heuvel. ‘He doesn’t expect his co-workers to be at work eleven hours a day. He himself isn’t either. We live in the same town, and I often see him taking his kids to school, by bike.’ ‘He’s not trying to turn the Hubrecht Institute into an MIT clone’, says Van Rheenen. ‘The main difference? At MIT, research groups are forever trying to one-up one another. Everyone is in competition. The Hubrecht Institute is also performan-

ce-oriented, but Van Oudenaarden likes his institute with its specific Dutch flavour. For example, as soon as he was appointed the new director opened every door to his own research group. He started talks with scientists from other teams and came up with new ways in which they could assist one another. Co-operation became the magic word. ‘There are so many examples’, Van Rheenen recounts. ‘Recently, my group used highly sophisticated cameras to record how stem cells in mice adapt into mammary gland cells. Subsequently, Van Oudenaarden dived into individual cells, using his technology to collect more precise data on RNA expression. Both methods are unique, yielding insights on the way cells are supposed to function. That, in turn, allows us to better determine which kind of glitch could theoretically lead to cancer’, explains Van Rheenen. Since then, cooperation has become ingrained in the Institute’s culture; collaborations are even forged across the coffee table between PhD candidates. ‘Everyone realises that elbowing one’s way to the front is not necessarily appreciated.’ Van Rheenen concludes. Colleagues are unanimous in their verdict: as director, Van Oudenaarden has continued to excel. Korswagen: ‘Filling Clevers’ shoes was no easy task, but he succeeded, on his own terms.’

Single-cell or multicellular? In the archipelago of science, full of isolated isles of research, Van Oudenaarden has emerged as its ideal physicist-biologist, researching-directing, rocking, geeky, Dutch-American competitive teamoriented builder of bridges. In the evolution of life, the transition from single-cell to multicellular life was a crucial stage. Suddenly individual cells were no longer fated to fight amongst themselves, but could strive towards higher goals, each through their own specialisation. That is exactly how Van Oudenaarden envisions the Hubrecht Institute. Individual research cells should not compete, but rather strengthen each other like cells of a multicellular life form, working towards a transcendent objective: to accrue knowledge. As Spinoza wrote: the aim should be to be to find that which is unlimited and eternal, and can be owned by all. Utrecht Life Sciences | New Scientist | 29


insight

Project Exposome The human genome has largely been mapped. Many congenital disorders have come to light as the cause, or at least a factor in a wide variety of diseases. Apart from genetic factors, however, there are many culprits coming in from outside. More than 70 percent of all chronic illnesses have extraneous triggers. The Exposome project, led by professor of Environmental Epidemiology Roel Vermeulen, charts all the factors we are exposed to, as well as how they might influence our health.

Climate Air pollution (e. g. particulates, CO2, ozone)

Stress

Lifestyle

Radiation

Infection

Urban or rural environment Work situation Exercise

Social-economic status Diet Social capital Chemical contaminations

30 | New Scientist | Utrecht Life Sciences

External exposome Outside factors such as lifestyle, air pollution and stress all have their influence on our risk of chronic disease. One example that is by now very well known, is the increased risk of cancer caused by smoking and polluted air.


INFOGRAPHIC: RIK SCHAGEN TEXT: KRISTEL KLEIJER SOURCE: ROEL VERMEULEN

Lifetime

Leaving trails

Internal exposome

Exposure to external factors can happen at different times in life, and therefore have different effects. For example, the winter famine at the end of the Second World War in 1944 raised the chances of Dutch girls getting breast cancer at the time. Yet this effect is not visible in women that had reached maturity by that year. The Exposome project studies the course of an entire lifetime and potentially age-related health impacts.

One of the scientists’ inquiries centers on the imprints that environmental factors leave on our biological system. A chain-smoking lifestyle, for one, has a specific impact on DNA structure. These changes may reflect not just the smoker’s behaviour at that moment, but when and how much that person has smoked as well. This enables the researcher to plot the effects of smoking on the body over time in even more detail.

The researchers are currently studying the impact of other exposures on metabolism, protein, RNA, and DNA regulation. Collectively, the measurements of these systems are called the internal exposome. One the one hand, the goal is to recognize imprints of exposure, by changes in the DNA for instance; on the other, to determine possible biological consequences like increased risk of cancer or cardiovascular disease.

Geographic information (satellites, teledetection, local detection)

Wearables

(sensors worn by humans)

Questionnaires

Biological scans

Smart homes

Data mining

Social media

Internet of Things

Measuring up Using brand new technologies such as tracking, environmental and health sensors, E-health apps, social media and biotechnology, researchers at Utrecht University are mapping the health effects of environmental agents.

Utrecht Life Sciences | New Scientist | 31


Interview Marianne Verhaar Text: Joris Janssen Translation: Bob van Toor

A

kidney, made to measure. Developing the bespoke organ is the holy grail for Marianne Verhaar (50), professor of Experimental Nephrology – the medical specialisation focusing on kidney disease – and head of the Nephrology Department at UMC Utrecht. As if that wasn’t enough, she also presides over what the UMC Utrecht has titled the ‘spearhead’ programme on regenerative medicine and stem cell research; the field of research attempting to stimulate the body to heal itself, and to avoid or even cure or even prevent disease. As spearhead programme president, Verhaar is at the helm of the hospital’s forage into this rapidly developing field of study. A field, moreover, that transcends nephrology, although that remains her primary expertise. From her third-floor office she works in almost full view of the dialysis machines. ‘Haemodialysis is an enormously draining form of treatment,’ she remarks as we start our conversation. ‘Therefore, we are greatly invested in turning it into a thing of the past.’

Tailoring the custom-made kidney

Apart from kidney specialist, professor and head of the nephrology ward, you have been named ‘spearhead programme president’ for regenerative medicine. What does a spearhead programme entail?

‘UMC Utrecht has selected six areas in which we want to excel; in medical care as well as education and research. Regenerative medicine is one of them. In Utrecht we are currently combining our strengths, together with the science and veterinary faculties for instance, and with the Hubrecht Institute, which performs fundamental research into stem cells. ‘Regenerative medicine adresses some of the great challenges of our time: aging and lifestyle related chronic disease; kidney failure, heart disease and mobility problems

Is it possible to activate our own bodies to avoid and cure disease? Can we work towards a future where haemodialysis will no longer be a taxing necessity for sufferers of kidney disease? Or, perhaps, even provide them with new organs? An interview with professor of Experimental Nephrology Marianne Verhaar (50), on the questions she spends her days on trying to answer. IRIS TASSERON

are just a few examples.’ Regenerative medicine could be the key to finding the solution to all these problems. No quick patch-ups, but sustainable, real solutions. For each of these illnesses, we are examining the possibilities for the body to regenerate itself.’ How do you get a body to heal itself?

‘Stem cells could play a crucial part in this process, as these cells are able to specialise and form all kinds of human tissue. They also contribute to the maintenance and repair of those tissues. To better understand stem cells, we conduct many experiments using mini-organs. By using mini-kidneys, for instance, we are learning how the body heals itself and how we could restore organs in the future of perhaps even make new ones.’ A mini-organ – should we imagine a smaller version of the real thing?

‘The term ‘mini-kidney’ is perhaps a bit robust for what it denotes; it’s not as if we have boxes full of tiny kidneys. They are small cell structures that don’t resemble a fully grown kidney at all, but do share the characteristics of a kidney’s tissue. ‘To make such mini-kidneys, we take cells from patients’ kidneys and cultivate tissue from them. By now, we can even extract the necessary cells from a patient’s urine, which is much less invasive.’ In what ways do you use these minikidneys?

‘Because the tissue has the characteristics of real kidneys, it allows us to study certain diseases. We can cause diseases in a minikidney, for instance a viral infection that often occurs in patients after a kidney transplant. We can then test different treatments and study which of these are effective in curing the infection. ‘We are also able to produce mini-kidneys out of tissue taken from patients with kidney cancer, to study that form of cancer and test treatments for it. Ultimately, we hope to make fully functional organs using minikidneys. A ‘kidney made to measure’, as the Dutch Kidney Foundation calls it. For now,

Utrecht Life Sciences | New Scientist | 33


Interview Marianne Verhaar Text: Joris Janssen Translation: Bob van Toor

A

kidney, made to measure. Developing the bespoke organ is the holy grail for Marianne Verhaar (50), professor of Experimental Nephrology – the medical specialisation focusing on kidney disease – and head of the Nephrology Department at UMC Utrecht. As if that wasn’t enough, she also presides over what the UMC Utrecht has titled the ‘spearhead’ programme on regenerative medicine and stem cell research; the field of research attempting to stimulate the body to heal itself, and to avoid or even cure or even prevent disease. As spearhead programme president, Verhaar is at the helm of the hospital’s forage into this rapidly developing field of study. A field, moreover, that transcends nephrology, although that remains her primary expertise. From her third-floor office she works in almost full view of the dialysis machines. ‘Haemodialysis is an enormously draining form of treatment,’ she remarks as we start our conversation. ‘Therefore, we are greatly invested in turning it into a thing of the past.’

Tailoring the custom-made kidney

Apart from kidney specialist, professor and head of the nephrology ward, you have been named ‘spearhead programme president’ for regenerative medicine. What does a spearhead programme entail?

‘UMC Utrecht has selected six areas in which we want to excel; in medical care as well as education and research. Regenerative medicine is one of them. In Utrecht we are currently combining our strengths, together with the science and veterinary faculties for instance, and with the Hubrecht Institute, which performs fundamental research into stem cells. ‘Regenerative medicine adresses some of the great challenges of our time: aging and lifestyle related chronic disease; kidney failure, heart disease and mobility problems

Is it possible to activate our own bodies to avoid and cure disease? Can we work towards a future where haemodialysis will no longer be a taxing necessity for sufferers of kidney disease? Or, perhaps, even provide them with new organs? An interview with professor of Experimental Nephrology Marianne Verhaar (50), on the questions she spends her days on trying to answer. IRIS TASSERON

are just a few examples.’ Regenerative medicine could be the key to finding the solution to all these problems. No quick patch-ups, but sustainable, real solutions. For each of these illnesses, we are examining the possibilities for the body to regenerate itself.’ How do you get a body to heal itself?

‘Stem cells could play a crucial part in this process, as these cells are able to specialise and form all kinds of human tissue. They also contribute to the maintenance and repair of those tissues. To better understand stem cells, we conduct many experiments using mini-organs. By using mini-kidneys, for instance, we are learning how the body heals itself and how we could restore organs in the future of perhaps even make new ones.’ A mini-organ – should we imagine a smaller version of the real thing?

‘The term ‘mini-kidney’ is perhaps a bit robust for what it denotes; it’s not as if we have boxes full of tiny kidneys. They are small cell structures that don’t resemble a fully grown kidney at all, but do share the characteristics of a kidney’s tissue. ‘To make such mini-kidneys, we take cells from patients’ kidneys and cultivate tissue from them. By now, we can even extract the necessary cells from a patient’s urine, which is much less invasive.’ In what ways do you use these minikidneys?

‘Because the tissue has the characteristics of real kidneys, it allows us to study certain diseases. We can cause diseases in a minikidney, for instance a viral infection that often occurs in patients after a kidney transplant. We can then test different treatments and study which of these are effective in curing the infection. ‘We are also able to produce mini-kidneys out of tissue taken from patients with kidney cancer, to study that form of cancer and test treatments for it. Ultimately, we hope to make fully functional organs using minikidneys. A ‘kidney made to measure’, as the Dutch Kidney Foundation calls it. For now,

Utrecht Life Sciences | New Scientist | 33


that is quite complicated. We can’t just sow a mini-kidney and watch it grow into a beautiful, functioning organ.' What remains to be done, until we will be able to produce custom-made kidneys?

‘Apart from the need for all the right kinds of cells, they all have to end up in the right places. The functioning of a kidney, depends largely on the arrangement of its cell structures. One potential strategy to realise this is to make a kind of mould, which you could make out of an organ donor’s kidney of insufficient quality to transplant. ‘By rinsing such a donor kidney with a special soap solution, it’s possible to remove all cells inside it. That leaves you with a sort of skeleton, retaining the original tissue structure but devoid of cells. You can then reintroduce new cells cultured from a patient . Currently, this method is not sufficiently developed as to be viable; it yields a kidney that barely functions.' Are there options apart from the method using a mould?

‘A structure like that, with specific cells in the right places, might also conceivably be printed. The printer you would use actually isn’t that different from an inkjet printer, except that it prints a sort of gel with cells in it instead of ink. For small structures it’s already working reasonably well, but printing larger cell structures is much more complex. A prominent nephrologist has demonstrated before that it is possible to print an entire kidney in form, yet without any functionality whatsoever. And it’s the function we need in the first place! ‘One further option that’s promising is the use of biomaterials: smart materials that can influence cells’ behaviours. By secreting certain substances, for instance; substances that steer cells in a certain direction or have them perform functions. To this end, we cooperate intensively with the Technical Universities of Eindhoven and Twente, among others.’

CV

interview

Marianne Verhaar Born 1967 in Rotterdam 2017 NWO Gravitation grant: Materials-driven regeneration and start of RegMedXB consortium 2015 Principal Investigator at CVON-Dutch Heart Foundation consortium RECONNECT 2015 President of spearhead Regenerative Medicine and Stem Cells, one of UMC Utrecht’s six Spearhead Programmes 2009 Professor of Experimental Nephrology, Utrecht University 2008 NWO VIDI grant and ASPASIA grant 2003 Head of the research laboratory for regenerative nephrology and vascular biology, UMC Utrecht 1999 PhD, cum laude, ‘Determination and pharmocological modulation of endothelial function in patients’, Utrecht University

Are such partnerships common within regenerative medicine?

‘Working together is important in many fields, but it is crucial to regenerative medicine, as many parts of the puzzle have to be put together. That means working with doctors, fundamental researchers, technical and material experts and a plethora of other specialists. ‘The recently opened Regenerative Medicine Center Utrecht concentrates most of Utrecht’s regenerative medicine researchers under one roof, together with the Hubrecht Institute. This has given our research an immense boost. In this new re-

‘The term ‘mini-kidney’ is a bit robust, we don’t have boxes full of tiny kidneys’ 34 | New Scientist | Utrecht Life Sciences

search centre, the printers are literally next door to the scientists working on miniorgans. Soon we will be joined there by researchers from the Faculty of Veterinary Medicine. Morever, scientists of the Univerisity of Twente and Eindhoven University frequently visit our center. Being able to cooperate with so many different experts is incredibly motivating. ‘It is wonderful that this field of research is currently receiving a lot of attention and funding. The NWO Gravitation Grant, for example, allows to expand our collaborative research in biomaterials-driven medicine together with Eindhoven and Maastricht Universities. In partnership with these institutions, and those in Leiden and Leuven, a consortium called RegMedXB has been set up, to find solutions to such issues as kidney damage and diabetes. Altogether, we can muster a lot of brain power.’ Will that impact patients directly?

‘One imminent result that certainly will is the portable artificial kidney. That too is being developed through team effort in this case, together with the University of Twente and the Kidney Foundation, amongst others. Improved technology has allowed us to build an artificial kidney that’s smaller and lighter than today’s dialysis machines. We hope this piece of technology will significantly improve kidney patients’ lives, by providing them with a lot more freedom of movement than they currently have.’ What else may we expect from regenerative medicine, in say, the next ten years?

‘That’s hard to predict. It’s a little like the smartphone: who could have thought, in its early years, that a phone would bring about such drastic changes? That’s what science is like as well. I am convinced that in ten years’ time we will have a much more comprehensive understanding of how the body heals, and we will be able to better study disease and their potential treatments using mini-organs. ‘A complete, functioning kidney may not be within our reach within a decade, but we may develop functioning kidney tissue on a smaller scale. Moreover, we can use mini-kidney cells to further improve the portable artificial kidney. Whatever happens, I hope we will make important progress in improving the lives of kidney patients in coming years.'


Graduate School of Life Sciences The Graduate School organises all Utrecht University Master’s and PhD programmes focused on microorganisms, plants, animals, humans, the molecules of life, and health & disease. uu.nl/lifesciences

3 faculties -

Faculty of Science Faculty of Veterinary Medicine University Medical Center Utrecht

Over 1,750 PhD candidates

We offer 14 PhD programmes

One of the largest Graduate Schools in Europe

30% of our candidates are of international origin


back matter

Fungus This is an image of a colony of the Aspergillus restrictus fungus. It is a rather modest fungus. It isn’t the fastest grower, but an excellent survivalist in parched environments. The fungus was photographed in a deep frozen state (at -140 °C) with an electron microscope. At this magnification, images can only be recorded in black and white; artist Wim van Egmond added realistic colour to the photo. IMAGE AND TEXT JAN DIJKSTERHUIS

Utrecht Life Sciences special New Scientist  
Utrecht Life Sciences special New Scientist