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Are biosimilars here to stay?

Molecular diagnostics

The next big thing


Genome editing


Creating a Comprehensive Catalogue of Mammalian Gene Function

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Living in a golden age Welcome to the latest edition of Bioscience Journal which looks at medical advances that are changing lives. One of the advances concerns the global biosimilars market, which is continuing to grow as products emerge to replicate the effect of branded ones coming to the end of their patented lives.

John Dean

Editor in chief

Research by analysts Technavio forecast that the global biosimilars market will grow by 55.52% during the period 2016-2020 with reasons including the rise in the number of patents that are expiring. Also driving the market is the lower cost of biosimilars, which is seen by their supporters as a crucial factor as global populations age and health services find their budgets coming under pressure like never before. However, there still remain challenges for biosimilar companies trying to gain a foothold in the market in some areas, including the UK, with reticence on the part of some health trusts and clinicians. You can understand the reticence in a way as clinicians consider changing from products that they have known for years to those that they do not know so well. However, increasingly convincing clinical trials on biosimilars, the non-availability of some branded treatments and the continuing pressure on budgets would seem to suggest that biosimilars are here to stay. Also exciting a lot of interest is molecular diagnosis, a crucial step in the move towards personalised medicine. As our piece says, one of the rapidly growing concerns in medicine is the anxiety that a lot of drugs do not work for a large number of


the patients for whom they are prescribed. The reason could well be that diseases and conditions are more complex than first thought with sub-types which mean that a one-size-fits-all approach is not effective. Finding the right drug for an individual can be a question of trial and error so a technology that increases the potential for personalised medicine based on each patient’s molecular biology is both intriguing and exciting. Our piece examines some of the work being done to advance the approach with many researchers believing that the idea of improved targeting of treatments holds massive potential. Our other features and news pages also examine work being done to improve the efficiency of treatments, work which underlines the fact that this is a golden age for health research. There have been many breakthroughs down the centuries and some great researchers and physicians have graced the field but it is fair to say that never has the pace of advance been greater. However, this pace of change brings its own challenges. Improved health care means people live longer. Good news, surely? Well, yes, but older people tend to suffer from a greater range of illnesses than younger people, more illness means more pressure on health services and their budgets and societies find themselves contemplating worrying questions. Do we want to live longer if old age depends on a regimen on drugs with their side-effects and potential to counteract each other? The answer, I think, lies in research work which both increases quality of life and promises to reduce the effects of so many illnesses. I suspect that, given those kind of assurances, most people would opt to live as long as they can, which is why we should be grateful that we are around to witness this golden age.



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Contents 28






UK News


World News

22-25 Biosimilars 28-31 Molecular Diagnostics


34-38 The next big thing 40-42 Genome editing



John Dean



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Genes discovery could save young lives

Two genes that are switched on when a child is suffering from a bacterial infection have been discovered by scientists. The team behind the discovery say that it could allow doctors to quickly distinguish between a viral or bacterial illness and allow early identification of potentially deadly infections. The international team of scientists, led by researchers at Imperial College London and funded by the NIHR Imperial Biomedical Research Centre, hope to use the findings to develop a rapid test for use in hospitals and doctors’ surgeries. They say that this would enable conditions such as meningitis, septicaemia or pneumonia - which are caused by bacterial infections - to be detected more rapidly. The test would also prevent children with viral infections being unnecessarily prescribed antibiotics, which are only effective against bacteria. At the moment, when a child arrives at a surgery or hospital with fever, doctors have no quick method of distinguishing whether he or she is suffering from bacterial or viral illness. Diagnosis relies on taking a sample of blood or spinal fluid, and seeing if bacteria grows, which can take more than 48 hours. Professor Michael Levin, from Department of Medicine at Imperial College London, who is from the section for paediatric infectious diseases and led the study, said: “Fever is one of the most common reasons children are brought to medical care. “However, every year many children are sent away from emergency departments or doctors’ surgeries because the medical team thinks

they have a viral infection when, in fact, they are suffering from life-threatening bacterial infections which are often only diagnosed too late. “Conversely, many other children are admitted to hospital and receive antibiotics because the medical team are unable to immediately exclude the possibility of a bacterial infection but, in fact, they are suffering from a virus. “Although this research is at an early stage, the results show bacterial infection can be distinguished from other causes of fever, such as a viral infection, using the pattern of genes that are switched on or off in response to the infection. The challenge is now to transform our findings into a diagnostic test that can be used in hospital emergency departments or GP surgeries, to identify those children who need antibiotics.” The team studied 240 children with an average age of 19 months, who arrived at hospitals with fever across the UK, Spain, the Netherlands and the USA. Once the children were diagnosed with a viral or bacterial infection using traditional methods, the team studied the genes that had been switched on in the children’s white blood cells. Using RNA micro arrays, which measure changes in 48,000 genes simultaneously using only a small drop of each child’s blood, the team found two genes are switched on in bacterial infections. Further tests showed these genes, called IFI44L and FAM89A, predicted a bacterial infection with 95-100 per cent accuracy.


Dr Jethro Herberg, senior lecturer in paediatric infectious diseases at Imperial, and co-author of the research, said: “We are facing a growing threat from antibiotic-resistant bacteria. A large proportion of antibiotic use is driven by our inability to reliably identify the small number of children with bacterial infection from the much larger number with viral infection, who do not need antibiotics. “Fear of missing life-threatening infections like meningitis and septicaemia result in doctors often prescribing antibiotics and undertaking investigations such as lumber punctures just to be safe. A rapid test based on the two genes we have identified could transform paediatric practice and allow us to use antibiotics only on those children who actually have a bacterial infection.” Vinny Smith, Chief Executive of Meningitis Research Foundation, said: “This latest development is very exciting. Giving health professionals the tools to rapidly determine whether an infection is bacterial or viral will enable faster detection and treatment of meningitis and septicaemia.” The research team are now working on further studies to confirm the findings in larger numbers of children. Their study was funded by the NIHR Imperial Biomedical Research Centre and patient recruitment in the UK was supported by the Meningitis Research Foundation as well as by international funders in Spain and USA.



Drug ‘slows growth of breast cancer tumour’

Cancer Research UK scientists have found a new way to slow the growth of the most aggressive type of breast cancer. The team from Oxford University and the University of Nottingham found that using a drug called JQ1 can alter how cancer cells respond to hypoxia – or low oxygen – found in more than 50% of breast tumours overall and most commonly in triple negative breast cancer, the form of the disease that is hardest to treat.

Breathing easier

Scientists at the University of Southampton have discovered a potential way of preventing asthma. The research analysed the impact of the gene ADAM33, which is associated with the development of asthma. The studies in human tissue samples and mice, led by Hans Michel Haitchi, an MRC Clinical Scientist Fellow and Associate Professor in Respiratory Medicine at the University of Southampton, suggested that if you switch off ADAM33, the features of asthma will be reduced.

Automated DNA production opens Scientists in Edinburgh have opened the first fully automated DNA production facility in the UK. The Edinburgh Genome Foundry will design, build and test large sections of DNA using robotic processes. Researchers at the facility are seeking to create and modify long strands of DNA that can be used to equip cells or organisms with new or improved functions. The products that result could lead to advances such as programming stem cells for use in personalised medicines, developing bacteria that can detect disease in the gut or altering the DNA of biofuel crops to enable a higher yield.

Blooming marvellous

Scientists at the John Innes Centre have taken a big step towards understanding how plants initiate flowering. They have uncovered a previously unidentified step in the process of vernalisation, which links a gene responsible for flowering time to the proteins that regulate it.

Housed at the University of Edinburgh’s School of Biological Sciences, the Foundry is primarily funded by the Research Councils UK’s Synthetic Biology for Growth Programme. Jo Johnson, Minister of State for Universities, Science, Research and Innovation, said: “An even greater understanding of DNA, and the ability to construct and modify it, will lead to untold scientific discoveries that could save millions of lives around the world.” Professor Susan Rosser, Co-Director of the Foundry, and Chair in Synthetic Biology at The University of Edinburgh, said: “The Edinburgh Genome Foundry will allow us to construct DNA on a large scale and will support synthetic biology in the UK. This will help us both interrogate how cells and organisms operate and realise the many economically important applications of synthetic biology.”


The new finding could contribute towards the development of new varieties of crops adapted to produce food in a changing climate.



Bioscience to play crucial role in Alzheimer’s research

Bioscience is playing a key role in a new multimillion pound project which involves the most rigorous series of tests ever staged to detect Alzheimer’s disease. The Deep and Frequent Phenotyping study, which is funded by the National Institute of Health Research and the Medical Research Council (MRC), hopes to dramatically improve the success rate of clinical trials for treatments in Alzheimer’s disease. Costing £6.9 million, the research project has been designed to identify measureable characteristics, known as biomarkers, which can detect the occurrence of Alzheimer’s disease very early on in the progression of the disease - when a person may have no obvious symptoms. Between 2002 and 2012, 99% of clinical trials into treatments for Alzheimer’s disease failed with experts identifying a probable reason as the fact that treatments are being tested on those who already have irreparable damage to the brain. They say it is likely that treatments will be more effective in slowing or stopping the further onset of dementia at earlier stages of the disease. Also, by targeting people in the earlier stages, it should be possible to design better clinical trials for new treatments. The team, led by the University of Oxford, will work with colleagues at eight UK universities and the Alzheimer’s Society, with the project also receiving support from a coalition of biopharma companies. They will perform up to 50 tests on 250 volunteers from Dementias Platform UK, including tests that have never been used before to detect dementia. The tests will include wearable devices that will give researchers detailed information on people’s movement and gait, and sophisticated retinal imaging that will look at subtle changes affecting a person’s central and peripheral vision. An estimated 46.8m people worldwide were living with dementia in 2015, and with an ageing population in most developed countries, predictions suggest this number may double by 2050. Currently, there is no known cure for the disease and the few treatments available treat symptoms, rather than slow or stop its progression. Professor Simon Lovestone, lead researcher and Professor of Translational Neuroscience at the University of Oxford, said: “We know that Alzheimer’s disease starts long before it is noticed by those with the disease or their doctor.

“Previous studies have shown changes to the brain as early as 10 to 20 years before symptoms arise. If we can identify the biomarkers present in this very early stage, we have the chance of treating the disease earlier, which is vital if we are to prevent damage to people’s memory and thinking.” Dr Rob Buckle, director of science programmes at the MRC, said: “Our goal is to find treatments that can slow down or even stop the progression of Alzheimer’s disease. “Finding biomarkers for clinical trials is crucial for fast-tracking decisions as to whether a trial should stop or continue, and the faster we can find out which drugs work and which ones don’t, the faster we can benefit patients.” The partners involved in the study are: University of Oxford, University of Cambridge, University College London, King’s College London, West London Mental Health Trust/ Imperial College London, Newcastle University, University of Manchester, University of Edinburgh, Cambridge Cognition, Imanova, Aridhia, Exprodo, Sage Bionetworks, TrialSpark, Optos, IXICO, Berry Consultants, AstraZeneca / MedImmune and the Alzheimer’s Society.


• In a separate development, Aducanumab, an antibody developed by the University of Zurich, has been shown to trigger a significant reduction of harmful betaamyloid plaques in patients with early-stage Alzheimer’s disease. The researchers demonstrated in an early stage clinical study that, after one year of treatment with Aducanumab, cognitive decline could be significantly slowed in antibody-treated patients as opposed to the placebo group. Roger M Nitsch, professor at the Institute for Regenerative Medicine at the university, said: “The results of this clinical study make us optimistic that we can potentially make a great step forward in treating Alzheimer’s disease.” A total of 165 patients with early-stage Alzheimer’s disease were treated in the trial and the promising effects of Aducanumab are being further investigated in two large phase three clinical studies involving more than 300 centres in 20 countries throughout North America, Europe, and Asia and taking in 2,700 patients



Cancer course launched

A new generation of cancer researchers are being taught at the University of Essex in a new course.

Funding secured for stem cell work

The MSc Cancer Biology course will be led a team of experienced cancer researchers. Clinicians at the Colchester Hospital University NHS Foundation Trust will also be involved in teaching both at the hospital and at the University’s Colchester Campus. The students will benefit from the University’s links with external cancer research organisations, including Cancer Research UK’s Cambridge Institute.

New protein

The University of Nottingham has secured £1.2m to develop injectable stem cell-carrying materials to treat and prevent fractures caused by osteoporosis and other bone-thinning diseases. The experimental materials consist of porous microspheres produced from calcium phosphates - a key component in bones – to be filled with stem cells extracted from the patient. Researchers hope that the targeted therapy could offer a quick, easy and minimallyinvasive treatment that is injected into areas considered to be at high-risk of fracture to promote bone regeneration. The funding award, from the National Institute for Health Research (NIHR Invention for Innovation (i4i) Challenge Award), also supports the development of a prototype delivery device to inject stem-cell-loaded microspheres. Research leads Dr Ifty Ahmed and Professor Brigitte Scammell say that their aim is to develop a preventive treatment to address the growing issue of fractures occurring due to bone-thinning diseases, which is becoming more prevalent due to the worldwide ageing population.

Dr Ahmed, from the Faculty of Engineering at The University of Nottingham, said, “We would advocate a national screening program, using a DEXA scan, which measures bone mineral density, to identify people at high risk of fracture due to osteoporosis. “If we could strengthen these peoples bone before they suffered from fractures, using a simple injection procedure, it would save people the pain and trauma of broken bones and associated consequences such as surgery and loss of independence.” The NIHR grant will also fund a Patient and Public Involvement study on the suitability of the technology, gauging the opinions and personal experience of people affected by osteoporosis as sufferers or carers, for example. Osteoporosis-related conditions affect three million Britons and cost the NHS over £1.73bn each year, according to the National Osteoporosis Society.


A protein which will help scientists understand why nerve cells die in people with Alzheimer’s disease has been designed in a University of Sussex laboratory. In people with Alzheimer’s, Amyloidbeta (Abeta) proteins stick together to make amyloid fibrils which form clumps between neurons in the brain. It’s believed the build-up of these clumps causes brain cells to die, leading to the cognitive decline in patients suffering from the disease. University of Sussex scientists have created a new protein which closely resembles the Abeta but contains two different amino acids. It can be used for laboratory researchers working to understand the role Abeta plays in Alzheimer’s disease.

Diversity the key

Research by University of Exeter academics shows that genetic diversity helps to reduce the spread of diseases in crops by limiting parasite evolution. The researchers used a virus that can infect and kill bacteria. The bacteria defend themselves using an immune system, known as CRISPR-Cas, which captures random DNA fragments from the virus.



New asthma treatment is a ‘game changer’ The first new asthma pill for nearly 20 years has the power to significantly reduce the severity of the condition, according to a study led by the University of Leicester. The research funded by Novartis Pharmaceuticals, National Institute for Health Research (NIHR) and the EU (AirPROM), was described by the lead researcher as “a game changer for future treatment of asthma.” Fevipiprant (QAW039) significantly decreased the symptoms, improved lung function, reduced inflammation and repaired the lining of airways. The drug is currently being evaluated in late stage clinical trials for efficacy in patients with severe asthma. A total of 61 people took part in the research. One group was given 225mg of the drug twice a day for 12 weeks and the other participants were assigned to a placebo group. Fevipiprant and the placebo were added to the medications the participants were already taking. The study was designed primarily to examine the effects on inflammation in the airway by measuring the sputum eosinophil count, an inflammation measurement of a white blood

cell that increases in asthma and is used to assess the severity of the condition. Professor Christopher Brightling, who is a NIHR Senior Research Fellow and Clinical Professor in Respiratory Medicine at the University of Leicester, led the study at the NIHR Respiratory Biomedical Research Unit, which is based at the Glenfield Hospital in Leicester. He said: “A unique feature of this study was how it included measurements of symptoms, lung function using breathing tests, sampling of the airway wall and CT scans of the chest to give a complete picture of how the new drug works. “Most treatments might improve some of these features of disease but, with Fevipiprant, improvements were seen with all of the types of tests. “We already know that using treatments to target eosinophilic airway inflammation can substantially reduce asthma attacks.

“This new treatment, Fevipiprant, could likewise help to stop preventable asthma attacks, reduce hospital admissions and improve day-to-day symptoms- making it a ‘game changer’ for future treatment.” Gaye Stokes, 54, from Grantham in Lincolnshire, who has had severe asthma for 16 years and was part of the Fevipiprant group, said: “I knew straight away that I had been given the drug. I felt like a completely different person. I had more get up and go, I was less wheezy and for the first time in years I felt really, really well. “For me, it felt like a complete wonder drug and I can’t wait for it to be available because I really think it could make a huge difference to me.” Professor Brightling said that the latest advance underpinned the work of the Leicester Precision Medicine Institute, a Centre of Excellence involving the University of Leicester and the NHS in Leicester.

“A unique feature of this study was how it included measurements of symptoms, lung function using breathing tests, sampling of the airway wall and CT scans of the chest to give a complete picture of how the new drug works.” 10



The cancer chaperones Heat shock proteins (HSPs) were originally identified as heat inducible gene products that had a role in cell survival. We now know that many HSPs are not heat inducible and that these highly conserved proteins have many roles in normal and stressed cells. In this article, Professor John HH Williams, will restrict himself to the role of HSPs in cancer cells. It has long been recognised that levels of HSPs tend to be elevated in cancer cells and as a result researchers have been interested in the role of HSPs in tumour development. At the Chester Centre for Stress Research we have been interested in the potential for HSP inhibition in cancer therapy – focusing specifically on Hsp27, Hsp72 and Hsp90. Two of the HSPs, Hsp27 and Hsp72, have been shown to be important to cell survival under a variety of stress situations – for example elevated temperature or heavy metal exposure. Both of these proteins bind to partially denatured proteins and allow refolding, they are therefore anti-apoptotic. One of the features of cancer cells is that they are resistant to apoptosis, so there is obviously potential for targeting Hsp27 or Hsp72. By using specific inhibitors or siRNA we have shown that targeting either Hsp27 or Hsp72 does reduce transformed cell line viability. However, when applied to primary cells the picture is less clear, because we see a high degree of variability in the response, although it is less pronounced in Chronic Lymphocytic Leukaemia (CLL) than in colorectal cancer. The response in colorectal cancer primary cells suggest a high degree of specificity in the dependency of the cancer cell to HSP depletion.

Cancer research has been heavily influenced by the concept of ‘The Hallmarks of Cancer’ proposed by Hanahan and Weinberg in 2001 and then renewed in 2011. Hsp90 is a protein that has chaperone activity, but also acts as a scaffold holding many receptor and signal transducer complexes in active confirmation. As many signal transduction pathways are highly active in cancer cells, Hsp90 is a target that may impact on many, if not all, the hallmarks of cancer. There are a large number of Hsp90 inhibitors and these do indeed kill cancer cells, whether used in isolation or in combination with other chemotherapeutic agents. However, we again find that the inhibitors are very efficient in transformed cells, but that there is great variability in response in primary cells.

be related to the fact that Hsp90 inhibitors tend to induce heat shock factor activity and therefore stimulate Hsp27 and Hsp72 production – making the cancer harder to kill! We would argue that the HSP inhibitors should be used with the target patient in mind and that, as highlighted in other studies, we need a personalised approach to the chemotherapeutic strategy. Most research at present focuses on the genetics of personalised therapy. We suggest that a chaperone/HSP fingerprint of the tumour may also be worth exploring.

When we examine the literature we find that there is overwhelming evidence that HSPs have an important role in the initiation, development and maintenance of the tumour phenotype. Naturally, pharmaceutical companies have put considerable effort into the development of Hsp90 inhibitors. Many of these inhibitors have entered clinical trials only to be withdrawn. Some for a lack of clinical activity, others because they seem to increase metastasis. This latter effect may




Dempsey, N.C. et al (2010) Cancer Letters 296, 257-267. Dempsey, N.C. et al. (2010) Journal of Leukocyte Biology 87, 467-476. Dempsey N.C. et al (2011) Methods Mol Biol. 2011;787:155-64. Hanahan, D. & Weinberg, R.A. (2011) Cell 144: 646-674. Lee, S.L. (2015) In Heat Shock Protein-Based Therapies (Ed A.A.A. Asea and S. K. Calderwood) Springer Lee, S.L. (2016) PhD Thesis



HIV research provides cause for optimism Research into vaccines to prevent HIV infection are offering new hope for those vulnerable to the condition, an international conference was told. Delegates attending the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa, were told about advances in the development of novel vaccines in the field of antibody mediated prevention (AMP). They heard about encouraging results from the HVTN 100 study, conducted by the USbased HIV Vaccine Trails Network (HVTN) in partnership with South African research sites. HVTN 100 tested the immune responses of South African volunteers to a modified version of the RV144 regimen, the only HIV vaccine regimen to show efficacy to date. The original RV144 vaccine reduced the HIV infection rate among study participants in Thailand by 31% over three and a half years. HVTN 100 Protocol Chair Linda-Gail Bekker, who is also Deputy Director of the Desmond Tutu HIV Centre in Cape Town and International AIDS Society President-Elect, said: “HVTN 100 used the same vaccines that RV144 tested, but made them specific to the Clade C subtype of HIV, which is widespread in southern Africa. “We also changed the adjuvant used with one of the vaccines, with the goal of eliciting a more powerful immune response, and added a booster injection to prolong the period of protection.

“Interim results from HVTN 100 provided the green light for a Phase III efficacy trial on the modified RV144 regimen. Criteria for the goahead centred on the percentage of HVTN 100 vaccine-recipients who displayed a range of immune responses and the strength of those responses. “All the criteria were met unequivocally and, in many instances, the HVTN 100 outcomes exceeded both our own criteria and the immune responses seen in RV144.” Larry Corey, HVTN Principal Investigator, said: “It is gratifying to see vaccines that were designed and manufactured specifically for South Africa meet and even exceed the criteria established to advance them into the large efficacy trial. HVTN 702 is a pivotal study that could lead to a licensed HIV vaccine in South Africa – the first preventive HIV vaccine worldwide.” HVTN 702, a placebo-controlled study, will begin enrolling 5,400 HIV-negative men and women at 15 research sites across South Africa before the end of 2016. Participants will receive five injections over the course of a year and be followed-for two years to establish whether the vaccine elicits a sustained protective effect. The trial will also seek to confirm earlier findings from HVTN 100 that the modified RV144 regimen is safe.


The work fits in with other work in the field, the conference heard. A major difficulty in the field of HIV vaccine development is the extraordinary capacity of HIV to mutate and evade the antibodies that might block it. A landmark event in this field of research was the start of the first large-scale human trials to evaluate whether a bNAb called VRC01, given by infusion, is effective in preventing HIV. The first of the two studies, HVTN 704/HPTN 085, commenced in March in the United States. It will enrol 2,700 gay men and transgender individuals who have sex with men in the US, South America and Europe. The second study, HVTN 703/HPTN 081, began in June in South Africa and will enrol 1,500 heterosexual women in seven sub-Saharan African countries. Researchers agree that the greatest value of the studies may be the scientific insights they yield for future vaccine development. Laboratory analysis of how bNAbs block HIV’s entry into healthy cells has already provided invaluable information for vaccine scientists and more lessons are expected.


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Starfish help solve evolutionary puzzle Biologists from Queen Mary University of London (QMUL) have discovered that the history of a hormone responsible for sexual maturity in humans can be traced to genes of starfish. Puberty and sexual development in humans is triggered by the release of the brain hormone gonadotropin-releasing hormone or GnRH. It was already known that fruit flies (Drosophila) have two GnRH-like hormones – one that mobilises stored fats to power flight (adipokinetic hormone or AKH) and another that makes insect hearts beat faster (corazonin). What was missing was information from other invertebrate animals that are more closely related to humans than insects. Scientists at QMUL’s School of Biological and Chemical Sciences, working in collaboration with the University of Warwick and KU Leuven in Belgium, discovered that starfish have two GnRH-like hormones, just like in fruit flies. Professor Maurice Elphick, who led the research team, said: “About half a billion years ago there were animals swimming in the oceans that would have had just one gene that coded for a GnRH-type hormone.

GnRH-like hormones that we find in fruit flies and starfish. But somewhere along the evolutionary lineage that gave rise to humans, the corazonin-type hormone was lost.” What is not clear yet is how it is that the ancestors of humans were able to get by with just one GnRH-type hormone. First author and PhD student Shi Tian, said: “We are investigating where the genes

encoding the two GnRH-like hormones are expressed in the strange five-sided bodies of starfish. With this information it may then be possible to find out what these hormones do in starfish.” The work was supported by the Chinese Scholarship Council and grants from the Biotechnology and Biological Sciences Research Council and the Leverhulme Trust.

About half a billion years ago there were animals swimming in the oceans that would have had just one gene that coded for a GnRH-type hormone.

“But then this gene duplicated and the two copies ultimately gave rise to the two




Research increases gene understanding

Francis Crick Institute scientists have discovered that a gene in fruit flies called ‘spidey’ regulates a key lipid-metabolising enzyme involved in cell growth and proliferation. Researchers found that spidey is important for keeping the brake on PI3K, preventing it from driving the inappropriate overgrowth of liver-like cells called oenocytes. The work may be helpful in treating tumours. Alex Gould of the Crick, who led a team including scientists at the University of Nevada, said: “Our findings used the power of fruit fly genetics to identify a new regulator of the lipid-metabolising enzyme phosphoinositide 3-kinase (PI3K). PI3K is an important enzyme as it drives the growth and proliferation of many types of cells including cancer cells.”

Funding creates opportunities for African scientists African research teams in Ivory Coast, Kenya, Senegal and Uganda have been awarded support to conduct world class health research and train the next generation of the continent’s scientists.

Initiative a success in treating hepatitis B

The Wellcome Trust has committed a further £21 million to the DELTAS Africa initiative, which aims to improve health in Africa through research.

Research into Africa’s first ‘screen-and-treat’ programme for hepatitis B suggests that the initiative may reduce deadly complications of the virus.

January 2014 in a collaboration between Imperial College London, the MRC Unit The Gambia, the Gambian Ministry of Health and Social Welfare and the National Public Health Laboratories.

The new findings from researchers at a number of international institutions suggest that the initiative is also cost-effective.

The study found that 9% of individuals and 13% of potential blood donors tested positive for the hepatitis B virus. However, of those screened only 4% of the individuals tested were deemed to have infection severe enough to require treatment with antivirals.

The region most affected by hepatitis B is SubSaharan Africa, where 80 million people are infected. To catch hepatitis infection earlier, before it causes conditions such as liver damage or cancer, the research team ran a pilot study testing people for the virus in communities in The Gambia, West Africa. The programme, called PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) was carried out between December 2011 and

In the so-called ‘screen and treat’ programme, the team used a cheap instant test to screen 6,000 people for the virus and referred infected individuals for further liver tests and treatment.

Dr Stefan Wiktor, lead of the Global Hepatitis Programme at the World Health Organisation, said: “We recently adopted a global strategy with a goal to eliminate hepatitis infection by 2030. To reach this goal, we will need innovative approaches, such as that developed by the PROLIFICA team, to provide testing and treatment services to as many people as possible.”


Four new research programmes will address a range of health needs, from emerging infectious diseases to neonatal health, population health and elimination of malaria.



Scientific team develop new type of rice

A team of Chinese and British researchers have developed a new form of more resilient rice.

ammonium ions in the soil, which are taken up by the plant roots.

This enabled them to take up much more nitrogen, as well as more iron and phosphorus. As a result, the plants gave a much higher yield of rice grain, up to 54% more yield in some trials, and their nitrogen use efficiency increased by up to 40%.

Dr Xiaorong Fan and Prof Guohua Xu, from Nanjing Agricultural University, in China, working with Dr Tony Miller, from the UKbased John Innes Centre, have developed rice crops with an improved ability to manage their pH levels, enabling them to take up significantly more nitrogen, iron and phosphorous from soil and increase yields,

For the plant to thrive, getting the right balance of nitrate and ammonium is important; too much ammonium and plant cells become alkaline, too much nitrate and they become acidic. Upsetting the pH balance also means the plant’s enzymes do not work as well, affecting plant health and crop yield.

The work is important because rice feeds 50% of the world’s population and has retained the ability to survive in varied conditions, including flooded paddy fields where the soggy, anaerobic conditions favour the availability of ammonium and much drier, drained soil, where increased oxygen means more nitrate is available. Another important reason why the work is significant is that nitrogen fertilizer is a major cost in growing many cereal crops and its over-use has a negative environmental impact. The nitrogen that all plants need to grow is typically available in the form of nitrate or

The international team has been working out how rice plants can maintain pH under these changing environments. They focused on a gene in rice called OsNRT2.3, which creates a protein involved in nitrate transport. The gene makes two slightly different versions of the protein OsNRT2.3a and OsNRT2.3b. Following tests to determine the role of both versions of the protein, the researchers found that OsNRT2.3b is able to switch nitrate transport on or off, depending on the internal pH of the plant cell. When this ‘b’ protein was overexpressed in rice plants they were better able to buffer themselves against pH changes in their environment.


Dr Miller said: “Now that we know this particular protein found in rice plants can greatly increase nitrogen efficiency and yields, we can begin to produce new varieties of rice and other crops. “These findings bring us a significant step closer to being able to produce more of the world’s food with a lower environmental impact.” The new technology has been patented by PBL, the John Innes Centre’s innovation management company, and has already been licensed to three companies to develop new varieties of six different crop species. This study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and grants from the Chinese Government.



Scientific advance

Scientists at The Scripps Research Institute in the United States have taken a big step toward the laboratory re-creation of the “RNA world,” which is believed to have preceded modern life forms based on DNA and proteins. The results show that the scientists have succeeded in creating a ribozyme that can serve to amplify genetic information and generate functional molecules.

Ebola development

Scientists at The Scripps Research Institute (TSRI) in the United States have developed a high-resolution view of how the experimental therapy ZMapp targets the Ebola virus. The study is the first to show how an antibody in the ZMapp drug cocktail targets a second Ebola virus protein, called sGP, whose vulnerable spots had previously been unknown.

Bioscience sector shows its worth A new study has shown that employment within the US bioscience industry has increased for the past four years. The report shows a growth in employment in the sector of nearly 10% since 2001, making it the best performing of the country’s technology sectors. The report, The Value of Bioscience Innovation in Growing Jobs and Improving Quality of Life 2016, launched as part of the BIO International Convention in San Francisco, found that US bioscience firms employ 1.66 million people, including nearly 147,000 high-paying jobs created since 2001. The average annual wage for a US bioscience worker reached $94,543 in 2014, earnings that are $43,000 greater, on average, than the overall US private sector wage of $51,148. The report further shows that since 2012, the bioscience industry has grown by 2.2% with four of its five major subsectors contributing to this overall job gain. Two of the subsectors—research, testing, and medical labs and drugs and pharmaceuticals—

led growth during the two-year period with both increasing employment by more than 3%. The survey is the seventh in a biennial series developed in partnership by TEConomy and the Biotechnology Innovation Organization (BIO). Jim Greenwood, President and CEO of the BIO, said: “This report highlights the long-term expansion of our industry and the significant impact of the high-paying jobs that come with developing the innovative technologies that are helping to heal, fuel and feed the world.” Ryan Helwig, Principal and Project Director with TEConomy Partners, said: “The bioscience industry continues to prove its economic value by driving US economic growth through innovation but beyond this economic value the industry is contributing value to patients every day through improvements to their quality of life.”


TSRI Professor Erica Ollmann Saphire, who co-led the study with TSRI Associate Professor Andrew Ward, said: “This is the roadmap we need to target the right molecules in infection.”

Study confirms healthy eating benefits

An American study has confirmed that consuming higher amounts of unsaturated fats is associated with lower mortality. The study by Harvard T.H. Chan School of Public Health, which followed people for more than three decades, found that higher consumption of saturated and trans fats was linked with higher mortality compared with the same number of calories from carbohydrates. Replacing saturated fats with unsaturated fats brought about substantial health benefits.



Polymer containment provides advantage for biologic drug delivery By Graham Reynolds,

Vice President & GM, Global Biologics West Pharmaceutical Services, Inc. For drug manufacturers, one of the early considerations for any container system is likely to be the interaction between the drug and the container closure system. Many companies evaluate both a glass and plastic option at an early stage of the development process to ensure that they have an appropriate solution that may help to optimize time to market and ultimate effectiveness and quality of the product. As part of compatibility testing, interaction with any materials that might be present in the system are examined. With more than 90 years’ experience as a leader in containment for injectable medicines, West is keenly aware that using the wrong container and container closure system can put patients in jeopardy, or cause delays in getting the drug to market. Because of potential incompatibility with biologics and other complex or high-viscosity drug products—that can inhibit progress through the drug development and commercialization process--glass may not be the right choice for highly sensitive molecules. West’s Daikyo Crystal Zenith cyclic olefin polymer offers a break-resistant, high-performance alternative to glass for complex drugs. Large molecule drugs require a level of stability that must be considered at every step of the manufacturing and packaging process. In cases of a combination product (when a drug container is incorporated into a mechanical delivery device) there needs to be a consideration of the tolerances of the various

elements, and the impact on functionality. Daikyo Crystal Zenith offers the ability to create custom shapes and designs with tighter dimensional tolerances, and has benefits when considering combination systems. Polymer components are also more resistant to breakage during the shipping, handling, manufacturing and throughout the overall supply chain, drastically reducing patient risk. The larger doses and high viscosity of biologics must also be considered when determining how to deliver biologics to patients comfortably and effectively. For example, the traditional volume limit for a conventional glass syringe and auto-injector is 1mL, but the high concentrations necessary of a novel biologic often exceed that limitation. In addition, a higher dose volume may enable less-frequent dosing, and the improvement of patient adherence and outcomes. Manufacturers should consider the final method of drug delivery at an early stage in the development process in addition, if the drug container has to be integrated into a delivery system as part of a combination product, early understanding is essential to ensure that the necessary work is done to support regulatory submissions. An example of an integrated solution for containment and delivery is West’s SmartDose technology platform, which allows patients to self-administer large volumes of medication in accordance with their prescribed treatment over a longer period of time. Featuring a silicone-free Daikyo Crystal Zenith® cartridge and a Flurotec® coated piston containment system, the SmartDose platform was


developed through extensive human factors testing and analysis to understand the interaction between the patient and the delivery system. The SmartDose platform adheres to the patient’s body, usually on the abdomen, so patients can be hands free during administration. Following extensive development, validation and scale-up, West was able to announce earlier this year the first FDA-approval of a biologic drug using the SmartDose technology. This followed the first approval of a biologic in a Daikyo Crystal Zenith vial, further validating the significant opportunity that polymer containment systems provide. As more attention is paid to the interaction between biologic therapies and primary drug containers, finding solutions to these challenges has taken on an increased urgency in order to protect patients, enhance therapeutic outcomes, and to prevent costly recalls. By closely collaborating early in the drug development process, pharmaceutical manufacturing companies and their packaging and delivery system partners can identify the specific needs around containment and delivery of both the drug product and the patients who will be using it. The result is an opportunity to effectively develop and optimize the manufacturing process accordingly to ensure a container closure system that facilitates quality, effectiveness and patient safety. SmartDose® is a registered trademark of Medimop Medical Projects Ltd., a subsidiary of West Pharmaceutical Services, Inc. West seeks partners for its SmartDose® injector technology platform. This platform is intended to be used as an integrated system with drug filling and final assembly completed by the pharmaceutical/biotechnology company.

When Performance Is on the Line No silicone oil, no tungsten, no glue Reduced protein aggregation Increased drug stability Highly resistant to breakage Tight dimensional control Flurotec film coated piston If these are the qualities your high-value biologic demands from a delivery system, look to West. The Daikyo Crystal Zenith® 1 mL long insert needle syringe system is the innovative solution that meets all these requirements and more.

Learn how West can help you deliver your high-value biologics safely. (800) 345-9800

West and the diamond logo and By your side for a healthier world™ are registered trademarks or trademarks of West Pharmaceutical Services, Inc., in the United States and other jurisdictions. Daikyo Crystal Zenith® is a registered trademark of Daikyo Seiko, Ltd. Daikyo Crystal Zenith and Flurotec technologies are licensed from Daikyo Seiko, Ltd. For complete contact information please visit Copyright © 2015 West Pharmaceutical Services, Inc. #9532 0216



Sequencing project targets diseases An exciting new project will see 1,000 people undergo whole genome sequencing and whole transcriptome sequencing using a novel testing platform provided by American company NantHealth. NantHealth has partnered with the University of Utah in to analyse the genomic profiles of people who have a history of rare and lifethreatening diseases and conditions in their families. The project will focus on researching the genetic causes of 25 conditions, including, breast, colon, ovarian, and prostate cancers, amyotrophic lateral sclerosis, chronic lymphocytic leukemia, autism, preterm birth, epilepsy, and other hereditary conditions. Genomic sequencing will be conducted with unique, comprehensive molecular tests offered by NantHealth. Researchers will use NantHealth’s genomic sequencing platform which integrates whole genome (DNA) sequencing, and RNA sequencing. By carrying out extensive testing, including analysis of germline and somatic samples, researchers will be able to explore the underlying genetic causes of conditions and diseases at the cellular level. Patrick Soon-Shiong, MD, Chairman and CEO of NantHealth, said: “Understanding the molecular profile and underlying genetic basis of various conditions and diseases, including cancer, will be accelerated through our

partnership with the University of Utah and its Utah Genome Project. “As the industry continues to focus on personalized medicine, it has become more important to have tests which can not only provide clinicians with information necessary to develop personalized treatment strategies for their patients, but also has the potential to help physicians identify treatments for debilitating diseases at a targeted level.” The university’s Utah Genome Project is a large-scale, genome sequencing and analysis initiative to discover new disease-causing genes and to develop genetic diagnostics and precision therapies that will transform healthcare. The project is unique among genome initiatives because, instead of studying unrelated individuals, it uncovers genetic signatures of disease and drug response in large families. It uses information from the Utah Population Database, the world’s largest repository of genealogies, public health and medical records, housed at the university. Dr Vivian S. Lee, Senior Vice President for Health Sciences and Dean of the School of


Medicine, University of Utah, and CEO of University of Utah Health Care, said: “By partnering with NantHealth and leveraging the power of genome sequencing, our researchers are now transforming our understanding of common diseases and how they should be treated.” Academic and industry genome experts in the US have joined together to launch iGenomX, a precision library construction company for next-generation sequencing (NGS) applications. Working within The Scripps Research Institute (TSRI), one of the world’s most notable research organisations, iGenomX has developed a patent-pending library platform that offers scientists increased control over the manipulation of DNA molecules. By applying precision biochemistry to digital biology, the company aims to deliver affordable and accurate applications including droplet-based linked-read assembly of human genomes.



Computational centre launched

Brown University, in Rhode Island in America, has launched a Center for Biomedical Research Excellence in Computational Biology of Human Disease to expand its research using computer analyses to fight disease. A new five-year $11.5 million grant from the National Institutes of Health means that Brown University can expand its research in computational biology. The work will support five early career faculty members as they tackle the genomics underlying diseases such cancer, preeclampsia and severe lung infections.

Agreement is signed

Swedish company Sprint Bioscience has signed an agreement with the Center for Hematology and Regenerative Medicine (HERM) at the Karolinska Institute in Stockholm to evaluate Sprint Bioscience drug candidates for the treatment of acute myeloid leukaemia, one of the most common forms of blood cancer.

Unlocking the secrets of the brain Scientists in America have more than doubled the number of known regions in the brain’s outer mantle, known as the cortex.

The findings could help add to the understanding of how the regions evolved and how they contribute to health and disease. The new map, based on research funded by the National Institutes of Health Human Connectome Project (HCP), divides the left and right cerebral hemisphere into 180 different areas. This can enable scientists to understand differences in the brains of patients with diseases such autism, schizophrenia, compared to healthy subjects. The team used MRI imaging to measure connectivity, topography, architecture and activity in the brains of 210 healthy male and female participants, and confirmed the findings in another independent group of 210 people.

They took MRIs of people both engaged in a task, such as listening to a story, and in a resting state. Nighty-seven new cortex areas were identified, and an additional 83 previously known areas were confirmed. Some areas found were located or oriented differently in a small number of participants, but the software algorithms were still able to map them correctly, providing a ‘fingerprint’ of each area. Lead study author Matthew Glasser, Ph.D., of Washington University in St. Louis said: “The ability to discriminate individual differences in the location, size and topology of cortical areas from differences in their activity or connectivity should facilitate understanding of how each property is related to behavior and genetic underpinnings.” The Human Connectome Project is a five year, large-scale attempt led by David Van Essen, Ph.D., that aims to usher in new information about the human brain by creating a map of neural connectivity to be shared with neuroscientists. The project used a specialized MRI machine to map the brains of 1,200 young adults.


The partnership enables the identification of patients who may benefit from a future drug and the work will be conducted on HERM’s and Sprint Biosciences’ respective research laboratories at Novum in Huddinge, Sweden.

Acquisition announced

Australian company Sasmar Pharmaceuticals has acquired Aquatrove Biosciences, an American biotechnology company focused on discovery, research and development in human reproductive health and fertility. Sasmar’s President and CEO John-Michael Mancini said “The acquisition captures the capability and know-how built up over many years by the specialised team at Aquatrove and facilitates the realisation of our plans for growth.”




biosimilars here to stay?

The global biosimilars market is continuing to grow as it changes the face of medical science, according to a number of new reports. Those working in the field argue that the growth can be attributed to the many benefits of using biosimilars, which are the follow-on versions of original biological medicines that are separately developed after the patent protecting the original product has expired. Biosimilars are designed to treat the same diseases as the original product but, although they have many similarities, they are not identical. Research by analysts Technavio forecast that the global market will grow by 55.52% during the period 2016-2020 with reasons including the rise in the number of patents expiring. Similar trends are acknowledged in another report, this time by Grand View Research in America, whose researchers also cite the importance of a number of major biological drugs nearing the end of their patents. They says that other advantages include the lower cost of the drugs as compared to patented biologics, the increasing demand to

reduce healthcare costs across the world and favourable outcomes in clinical trials for a range of drugs. Grand View estimate that, in 2015, Europe accounted for the largest market share of the global biosimilars market, followed by Asia Pacific. Indeed, the European market is the most advanced as it has been, according to the researchers, who say that is because Europe was the first to formulate a regulatory pathway and adopt the use of biosimilars more than eight years ago. Germany accounts for the maximum share followed by the UK, France, Spain, and Italy. North America is anticipated to be the fastest growing market over the next eight years with the Asia Pacific market expected to witness a lucrative growth as well with India and China leading the way.







Biosimilars ‘making progress in the UK’ However, there still remain challenges for biosimilar companies trying to gain a foothold in the market, with reticence on the part of health trusts and clinicians taking time to break down. The UK is an example according to the British Biosimilars Association (BBA), the expert sector group of the British Generic Manufacturers Association exclusively focused on biosimilars. The BBA, whose members include manufacturers in the development and production of biosimilar medicines, says that despite use in the UK since 2006, supportive NICE guidance and NHS England backing for the appropriate use of biosimilars, there remains a low up-take in some fields, compared to a number of other European countries. Warwick Smith, British Biosimilar Associations Director General, said: “We are seeing an increasing take-up of biosimilars in the UK but there is still some way to go. “I think one of the reasons take-up has not been as fast as it could have been is about culture. You have doctors who have been trained to prescribe a branded drug with which they are familiar and it has been an education process to persuade them to use a biosimilar instead. “In addition, in most cases the clinical trial data relates to the original patented product and clinicians have had to understand that those data apply to the biosimilar product as well.” The association says that, given that five of the top seven biologics will lose patent by 2020, biosimilars can play a profound role in the future of healthcare in the UK by offering more choice at competitive prices. According to the BBA, competition from biosimilars can free up resources to help fund new medical breakthroughs, with competition motivating producers of patent protected medicines to develop innovative products.

Warwick Smith Warwick said: “If you are a health trust under pressure to cut costs and you have a biosimilar that does the same job as a more expensive branded version, why would you not make the change? Indeed, NICE guidance says that if you have two drugs that do the same job a trust should go for the most costeffective option.” The BBA points as an example to data based on 2010 usage of human growth hormone (hGH) at The North Central London Formulary and Medicines Management Group at University College London Hospitals NHS Trust. The data suggests annual cost savings in excess of £200,000 per annum are

possible from a single centre if all patients were switched from originator hGH3 to biosimilar hGH. Warwick said: “Trusts can be assured that the regulators have ensured that the biosimilar is safe to use, although you can understand the view of patients concerned that there may be some variability in the way the biosimilar works. The point we make is that those variabilities exist in the originator as well. “I think we are making progress and more recent biosimilar products have had much stronger take-ups than the early ones.”

I think one of the reasons take-up has not been as fast as it could have been is about culture. You have doctors who have been trained to prescribe a branded drug with which they are familiar and it has been an education process to persuade them to use a biosimilar instead. Warwick Smith

British Biosimilar Associations Director General,




Conference to turn spotlight on biosimilars market

Biosimilars offering encouraging results in rheumatology One of the other areas in which biosimilars are attracting attention is rheumatology and an example of new products coming online was highlighted at the recent Annual European Congress of Rheumatology in London. Data demonstrating long-term efficacy, safety and immunogenicity for Benepali® (etanercept) and Flixabi® (infliximab) were presented to delegates by Samsung Bioepis, the joint venture between Samsung BioLogics and Biogen. Results of studies showed that in patients who were switched to Benepali there were no treatment, safety or immunogenicity issues and efficacy was sustained for up to two years. It was a similar picture with Flixabi. Both were both approved by the European Commission earlier this year and are commercialised in Europe by Biogen. Alpna Seth, Ph.D., Senior Vice President and Global Head of the Biosimilars Business Unit at Biogen, said: “Biosimilars can help more patients gain access and benefit from biologic therapies, while providing cost savings to healthcare systems and supporting future healthcare innovation.” Professor John Isaacs, Director of the Institute of Cellular Medicine at Newcastle University and consultant rheumatologist at the Freeman Hospital, said: “The integration of biosimilars in routine clinical practice is a crucial step to help patients’ access disease-modifying

biologic therapies from which they can significantly benefit. “Patient safety is of the utmost importance, and we are beginning to see a solid bank of data that, together with real-world evidence, will further establish the role of biosimilars.” Among those organisations offering a view on the increasing use of biosimilars is the British Society for Rheumatology, which supports the BSRBR Rheumatoid Arthritis Register run by the Arthritis Research UK Epidemiology Unit at the University of Manchester. The register tracks the progress of patients with severe rheumatoid arthritis, who are receiving biologic agents, to help monitor the safety and effectiveness of the treatments. A spokesman said: “We strongly recommend that all patients starting or switching to biosimilars should be registered with the BSRBR to allow the capture of the same robust systematic data on adverse effects that have been collected for the reference medicines. The data will ultimately allow clinicians and patients to make informed choices about treatment options.”


Biologics and biosimilars researchers from around the globe will gather for the 7th European Biosimilars Congress 2017 in Munich between May 15-17. The congress will bring together everyone from scientists, researchers and business development managers to CEOs, directors, IP Attorneys and Regulatory Officials. Themes due for discussion will include how biosimilar product development can deliver safe and efficacious biologic products to the market, how emerging biologics are helping patients with psoriasis, rheumatic arthritis, certain cancers, inflammatory bowel disease and how emerging biosimilar insulins are likely to become more important as patents for major branded insulin products start to expire in the next few years. Other themes will include how regulation impacts on the biosimilars market and what effect Brexit will have on the industry. More information is available at http://biosimilars-biologics. europe/



LacZ expression in adipose tissue in mice with the gene Sik1 inactivated. Mice have increased lean body mass and decreased total body fat amount

Creating an encyclopaedia of mammalian gene function The International Mouse Phenotyping Consortium (IMPC) is working to provide freely available information about the function of every gene in the mouse genome, based on the focused efforts of its 18 member organisations. Understanding health and disease in humans depends on knowing the function of some 20,000 protein-coding genes – yet the scope of our knowledge is limited to only a small fraction of these. To increase our understanding in this area, scientists at 18 research organisations in 11 countries have joined forces to systematically determine the function of every protein-coding gene in the mouse genome. The knowledge generated based on this resource will inform more targeted research into human disease. IMPC researchers are cataloguing gene function by creating knock-out mouse lines, in which a single gene has been inactivated, and collecting key molecular and phenotypic (i.e., physical features, health status) information in a consistent manner. For each knock-out, they conduct a series of tests to identify any abnormal characteristics relating to factors such as development, anatomy and behaviour. This provides valuable insights into the potential function of the inactivated gene.

Over the past five years the IMPC has produced data for more than 5,000 genes, and determined that approximately one third of all mammalian genes are essential for life.


Anyone visiting the IMPC web portal can search for data by gene, phenotype or human disease. Mouse lines and embryonic stem cells can be ordered for research through established repositories. To date more than 650 publications have used IMPC resources in their research with the list growing every week. If you are interested in a particular gene that the IMPC has not yet studied, you can register your interest, which helps the consortium prioritise. As the data resource grows and new findings emerge, it will be increasingly important for the IMPC to ensure the interface and software are clear, intuitive and fit for purpose. For example, they recently updated


their web interface to offer landing pages for different disciplines (e.g., bone, cardiovascular), which helps users find relevant information more quickly. IMPC researchers have also developed software for comparing images of embryos, both in 2D cross-sections and in 3D that can be rotated and zoomed in. The interface allows users to view embryos with inactivated genes alongside healthy embryos, which makes it easier to spot differences.


IMPC researchers are also developing automated algorithms that identify associations between mouse and human data. So far, they have discovered 129 human disease models – this is where the mice display many of the features of a certain human disease. 81 associations have been found between ‘lethal’ knock-out genes in mice and humans,



further exploration of these will help bridge an important gap in the study of rare and developmental disorders. The IMPC resource has also enabled new discoveries, for example very little was known about the gene FAM53B in mice or humans. Mice in which this gene had been deactivated had a decreased number of red blood cells and other phenotypes, which suggests that FAM53B is involved in growth and maturation of blood cells – and could be involved in certain types of anaemia. The researchers have also found links between this gene and Diamond-Blackfan anaemia, for which the genetic causes are unknown in 46% of patients.

Fourteen and a half day old embryonic mice. Micro-CT scans are of many embryos averaged into one where varying transparency reveals different layers of internal organs and structure


The data is now being harnessed by other scientists to identify genes implicated in specific areas and then look at them with ‘secondary phenotyping’ – that is performing more specific tests relevant to their research area. DMDD (Deciphering the Mechanisms of Developmental Disorders) is a project dedicated to understanding the genetic causes of developmental disorders and rare diseases. DMDD takes lethal lines produced by the IMPC and performs in-depth phenotyping, identifying abnormalities ranging from organ malformations down to problems at the level of individual nerves and blood vessels. Their image and phenotype data is also freely available online for further study.

The 3i project (Infection, Immunity, Immunophenotyping) is performing in-depth analysis of the immune system and looking at responses to infection. In both cases, hundreds of strains have been analysed.


The IMPC plans to generate 3,000 new mouse lines in the next five years. Using powerful gene editing technologies such as CRISPR/ Cas9, they will accelerate progress at reduced cost and higher efficiency than ever before. In addition, they will be phenotyping mice at later stages of life to better understand diseases associated with ageing.

Helmholtz Zentrum Munich (GMC)

PHENOMIN Jackson Lab

UC Davis

National Institute of Health (NIH)

MARC, Nanjing

Czech Centre for Phenogenomics (IMG)

Charles River Laboratories


MRC Harwell Institute Sanger Institute EBI

Toronto Centre for Phenogenomics (TCP) Children’s Hospital Oakland Research Institute

As the IMPC’s data resource grows, it will become an increasingly important tool for precision medicine – customising healthcare for individuals based on their genetic makeup. The IMPC is a good example of what can be achieved when scientists collaborate to achieve a common goal. The results of their efforts are freely available to spur exploration and discoveries that benefit humankind.

CNR Monterotondo (IMC)

Korean Mouse Phenotype Consortium

Riken BRC (JMC) NLAC NARLabs, Taiwan

Universitat Autònoma de Barcelona (UAB)

Baylor College of Medicine


Australian Phenomics Network



Targeting the

right treatment

at the right patient

One of the rapidly growing concerns in medicine is the anxiety that a lot of drugs do not work for a large number of the patients for whom they are prescribed. By Frances Griss Finding the right drug for an individual can be a question of trial and error so the future of treatment is for personalised medicine based on each patient’s molecular biology and an approach that splits diseases into sub-types according to their treatment, not the symptoms. Molecular diagnostics uses genetic markers or the proteins by which they express themselves to point clinicians towards an effective treatment first time. In addition the technique can be used to provide a firm diagnosis to differentiate between conditions exhibiting similar symptoms. The chemistry behind molecular diagnostics relies on the ability to amplify a sample of DNA before it can be accurately identified

and this is carried out using a polymerase chain reaction (PCR). Reactions require a repeated heating and cooling cycle in the presence of a primer, a short section of DNA which is complementary to the section you wish to amplify, and DNA polymerase. Hardware for carrying out the tests is constantly evolving with plenty of competition to develop everything from large-scale platforms to tiny portable, battery-operated versions weighing less than 500g, although the latter is not really intended for clinical use. The potential of the approach is that it removes guesswork, allowing specific diagnosis of individual pathogens which leads to more targeted treatment.







Companies announce

new developments

An example of the new approach is seen in the way that several companies have been working to accurately and speedily diagnose zika virus. In March, the US Food and Drug Administration gave authorisation to Roche for its Cobas Zika test which detects the infection using a newly-developed assay test in the company’s commercially available cobas 6800/8800 machinery. It is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from individual human blood donors. Roland Digglemann, Chief Operating Officer of Roche Diagnostics, said: “These fullyautomated high-volume systems provide solutions for blood services to detect the virus and ensure that potentially infected blood units are not made available for transfusion. “ The same platforms will process tests for a range of healthcare-acquired infections including Clostridium difficile and Methicillinresistant Staphylococcus aureus. More efficient diagnosis of these conditions enables infection control protocols to be implemented quickly as well as allowing for better-targeted treatment. Other infectious diseases where similar tests have been developed include both viruses and bacteria. They range from cytomegalovirus and Human papillomavirus to Mycobacterium tuberculosis. Sexually transmitted infections such as herpes and gonorrhoea can also be diagnosed using this technique. Markets are opening up for machinery which can process tests almost instantaneously, in close proximity to the patient and are as reliable as a major laboratory. Patients visiting a clinic or a hospital could, if the right machinery was installed, be tested, receive an accurate diagnosis and be prescribed the best treatment within a few hours. In February, Bristol-based company Atlas Genetics announced EU approval for a Chlamydia trachomatis test on its ultra-rapid io platform and has plans to introduce similar tests for other sexually transmitted infections including Gonorrhoea and Trichomonas vaginalis. The sample is placed in a disposable cartridge and an answer is produced in only 30 minutes, according to the company, all without compromising reliability.

CEO John Clarkson said: “STIs are on the rise and the rise and the faster a diagnosis can be made, the faster treatment can be given, not only benefiting the patient but also saving time and money.” The medical imperative has led to systems which can process large volumes of tests in only two or three hours. Even when sample have to be sent to outside laboratories, results can come back in much shorter timescales than with previous testing systems. The capacity of molecular diagnosis to achieve better outcomes for patients has been acknowledged by the World Health Organisation, particularly in relation to multidrug-resistant tuberculosis (MDR-TB). In May, the WHO announced that it was recommending the use of molecular diagnostic tests to identify patients who would benefit from a shorter, cheaper treatment regimen. The WHO said it would lead to better outcomes because patients would be more likely to see the treatment through to the end. Conversely, those patients resistant to some drugs would not be needlessly prescribed therapy to which they would not respond and which would only increase the likelihood of further drug-resistant strains of TB developing.


Dr Karin Weyer, co-ordinator of laboratories, diagnostics and drug resistance for the WHO global TB programme, said: “We hope that the faster diagnosis and shorter treatment will accelerate the much-needed global MDR-TB response. “Anticipated cost savings from the roll out of this regimen could be re-invested in MDR-TB services to enable more patients to be tested and retained on treatment.” In 2015, Arthritis Research UK announced that a consortium of scientists from around the world would be investigating the reasons some patients struggle to find a treatment for rheumatoid arthritis which works for them. One stream of research is looking for biomarkers which predict which drug will be effective, reducing the time between diagnosis and treatment. The charity says that more accurate prescription could save the NHS £13 to £18 million a year on its drugs bill. Professor Costantino Pitzalis, of Queen Mary University, London, joint leader of the MARURA Consortium, said: “We can’t continue to use biological therapy on a trial and error basis. We need to find biological markers to identify



patients who are likely to respond to the drugs they’re given. “As well as improving diagnostics and finding better outcome measures, we can accelerate the discovery of new targets and develop new drugs.” Advances are also being made in the diagnosis and treatment of various cancers including oesophageal cancer, which has recently been found to come in three distinct types, as identified by the International Cancer Genome Consortium. Each type has identifiable DNA differences. Professor Rebecca Fitzgerald, lead researcher on the project and based at the MRC Cancer Unit, University of Cambridge, said: “Our study suggests we could make changes to the way we treat oesophageal cancer.

We can’t continue to use biological therapy on a trial and error basis. We need to find biological markers to identify patients who are likely to respond to the drugs they’re given. Professor Costantino Pitzalis

“Targeted treatments for the disease have so far not been successful and this is mostly down to the lack of ways to determine which patients might benefit from different treatments. These new findings give us a greater understanding of the DNA signatures that underpin different sub-types of the disease and means we could better tailor treatment. “The next step is to test the best approach in a clinical trial. The trial would use a DNA test to categorise patients into one of three groups to determine the best treatment for each group and move away from a one-size-fits-all approach.” New disease-specific assays are being released all the time in this exciting and fast-paced branch of diagnostics. Competition is brisk as companies seek to tie assays into their analytical platform or produce a general assay for use across many different devices. In 2015, for example, Wirral-based Biofortuna appointed a new chairman, Ian Johnson, to oversee future growth in the company, which specialises in freeze-dried molecular diagnostic assays and offers a contract development service for in vitro diagnostics. It is not alone in taking an optimistic view of opportunities in the sector.




Trials offer hope to Duchenne Muscular Dystrophy patients Research into the rare disease, Duchenne Muscular Dystrophy, has changed dramatically. Ten years ago there were no clinical trials available and patients with the disease were unlikely to live beyond their early twenties. Today, thanks to the support of patients, researchers, charities, life sciences companies and support provided by the National Institute for Health Research, the outlook is very different. Duchenne Muscular Dystrophy (DMD) is a severe form of muscular dystrophy, characterised by progressive muscle weakness and wasting affecting legs and arms. It is caused by a mutation in the dystrophin gene and is typically diagnosed around the age of four years. Parents often first notice their son - the vast majority of those affected are boys - cannot run and jump around like other children. Steroids can only delay the progression of symptoms, there is currently no cure. Research into the condition is currently being carried out in several centres around the UK. The John Walton Muscular Dystrophy Research Centre – a collaboration between Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust - plays a leading role and is home to several trials into DMD, including studies with interventional drugs. Taking a drug from development to the point where it can be prescribed is a complex and time intensive process. Dr Michela Guglieri from the Centre tells us more about

the challenges and the human impact on those involved: “Clinical research is not easy, it often comes with an ethical dilemma [sic] and it’s important to present a study in a way that does not seem to be offering false or unrealistic hopes to families. You should offer people the chance to take part but not incentivise them to take part. I’ve learned that getting the correct outcome measure is very important; what do you want to measure and how can you measure it with all the appropriate safeguards in place. I’ve also learnt a lot about the commitment to taking part from the patient perspective.” What is the impact on patients and their families? Dr Guglieri explains: “We have families who are committed to travel from Ireland every week. In the ten years that I’ve practised here I’ve been able to work with the families of boys with DMD throughout the progress of the disease. I meet them at


the point they are diagnosed, throughout their ongoing care and management, and of course work with them as participants in our clinical trials. This has allowed me to develop experience of the disease and its progression and to build very strong relationships with the families. We have families travelling from Northern Ireland, Scotland and further afield who come to see us weekly or monthly.” One such family is the Johnston’s. Linda Johnston’s son, Pascal was diagnosed with DMD at the age of four. Linda became aware of clinical trials taking place into her son’s condition and Pascal is currently participating in a DMD clinical trial in Newcastle: “Pascal has a diagnosis of DMD and is aware that it is life limiting, however, you always have hope as a mam. I was told when he was four that he probably wouldn’t reach 14, but he will be 14 this year. After the diagnosis we spoke to consultants and were told that medical science is moving fast and that there are a lot of exciting things coming up. They



didn’t want to give us false hope but said things are in the pipeline, and sure enough ten years down the line, Pascal is on a drugs trial.” It can be a difficult decision for a parent to agree for their children to be involved in clinical research as there is always an element of the unknown. But parents like Linda understand that treatments will only progress and improve if people take part in research. She says: “We were guided all the way through and all of the checks were very rigorous. They explained that Pascal is the most important thing in this trial.” Such clinical trials are often the result of collaboration between healthcare providers like the NHS and the life sciences industry. Sophie Evett PhD, is the Country Study Start Up Lead for Pfizer UK and has set up DMD trials for Pfizer in Newcastle and other UK sites: “The current Pfizer DMD study is unique because it is a paediatric study and is time intensive for both patients and parents, the doctors, nurses, and pharmacists. The study also involves physiotherapists and MRI technicians, all of whom need to be trained prior to being able to perform our study. Because of the investment of time and energy required, we needed sites and research teams that could meet these requirements.” So how did Pfizer identify potential sites in the UK? Sophie continues: “The support that the National Institute for Health Research (NIHR) Clinical Research Network gave us was invaluable. They helped us identify suitable investigator sites, and when we decided to open more sites in the UK we asked them to go back out to their network and find some additional sites. We are very fortunate and in a unique position in England to have the NIHR Clinical Research Network.” “Through the Pfizer INSPIRE (Investigator Networks, Site Partnerships and Infrastructure for Research Excellence) Site Programme, Pfizer and the NIHR Clinical Research Network will work together to bring more clinical trials to the UK.”

The Johnston family, with Pascal, centre

The government-funded NIHR is the research arm of the NHS. The NIHR’s Clinical Research Network has a specific focus around supporting the delivery of clinical trials and studies - its mission is to make sure that clinical research is an integral part of healthcare for all. The approach of the Network is to provide the NHS with the support and facilities needed to make it easier for research to happen in England. Over the last decade it has worked hard to create a thriving environment for conducting large scale commercial contract clinical research. For example, since 2010/11 the median time for getting a study running in the NHS has dropped from 115 days to just 18 days in 2015/16 - an 82 per cent decrease. Supporting the life sciences in this and other ways is a priority for the NIHR. Commercial involvement in research into treatments

for diseases such as DMD can speed up the development and availability of new treatments, therapies and diagnostics for NHS patients like Pascal. As Linda Johnston says: “This trial may not be 100 per cent successful but it could lead on to something that is a medical breakthrough - it could be step one of a cure or a permanent plaster over the deletion (of the dystrophin gene). So for my part as Pascal’s mam, it gives me hope. It’s not a cure, but it’s hope.” “I discussed with Pascal that it may well be that at the end of the trial, they might not achieve what they hope to achieve. However, it won’t be a disaster because it will advise and steer them in other directions and to try other things. But fingers crossed, things seem to be going fine.” For further information about the NIHR study support service visit

I’ve learned that getting the correct outcome measure is very important; what do you want to measure and how can you measure it with all the appropriate safeguards in place. I’ve also learnt a lot about the commitment to taking part from the patient perspective. Dr Michela Guglieri




Technologies that promise to

change our world

These are exciting times in the world of bioscience with breakthroughs being announced in fields ranging from health research to biofuels development.

Since much of this edition of the Bioscience Journal is devoted to technologies promising to change the world in which we live, we asked a number of experts to make some predictions.




Exciting times in the field of asthma research One of the areas in which truly exciting advances are being made is asthma, one of the commonest chronic diseases on the planet. Professor Stephen Holgate, CBE, Chair of the Research Committee of the British Lung Foundation, said: “We are about to embark on a new and exciting phase in medicine and in the case of asthma we are seeing new therapeutics which target the specific pathways of the condition. “Up until now, we have used medicine to control the symptoms like wheezing when they come on, which is fine, but much more attention is now being paid to preventing it, “There is some exciting work being done. The UBIOPRED project is a good example. It is a research project using information and samples from adults and children to learn more about different types of asthma to ensure better diagnosis and treatment and they have identified six or eight subtypes of asthma.

concentrations of bio-organisms, so if we can find ways of reproducing the protective effects in susceptible families asthma and allergies might be prevented. “I do think that the next five years will see a string of breakthroughs in the way we treat and prevent respiratory diseases. “While COPD is behind asthma in terms of research, we could prevent a lot of it if we stopped smoking or intervened earlier in its development.”

Prof Stephen Holgate “That is exciting because current treatments treat just one or two so we can now do more to identify the specific nature of each subtype of the condition. “There is also some interesting research which shows that children in the womb who are exposed to animals on farms are protected from allergies and asthma. “We think that is down to pregnant mothers and young children being exposed to high


There is also some interesting research which shows that children in the womb who are exposed to animals on farms are protected from allergies and asthma.



Fledgling printing technology offers hope One of the big medical changes ahead could relate to the production of tissue for implants, combining 3-D printing technology and bioscience. Among those leading the way are scientists at the University of Bristol who have developed a new kind of bio-ink, which they say could eventually allow the production of complex tissues for surgical implants. The ink, which contains stem cells, allows 3D printing of living tissue, a process known as bio-printing, and contains two different polymer components, a natural polymer extracted from seaweed, and a synthetic polymer used in the medical industry. The synthetic polymer causes the bio-ink to change from liquid to solid when the temperature is raised and the seaweed polymer provides structural support when the cell nutrients are introduced. Lead researcher Dr Adam Perriman, from the School of Cellular and Molecular Medicine, said: “This kind of technology is at the cutting edge, but we are already seeing major benefits. For example, we can bioprint living tissue-like structures that can be used by other scientists or drug companies to reduce the need for animal testing. “Designing the new bio-ink was extremely challenging. You need a material that is printable, strong enough to maintain its shape

when immersed in nutrients, and that is not harmful to the cells. We managed to do this, but there was a lot of trial and error before we cracked the final formulation. “What was really astonishing for us was when the cell nutrients were introduced, the synthetic polymer was completely expelled from the 3D structure, leaving only the stem cells and the natural seaweed polymer. This, in turn, created microscopic pores in the structure, which provided more effective nutrient access for the stem cells.” The team’s findings could eventually lead to the ability to print complex tissues using the patient’s own stem cells for surgical bone or cartilage implants, which in turn could used in knee and hip surgeries. Adam said: “I think we are still at an early stage with these kind of technologies. Having said that, we are seeing big companies investing a lot of money into research and the past twelve months have seen an explosion, not just in technology, but in the applications for which it can be used. “I think the technology has potential and there is a lot of research being carried out. I have just started working, for instance, with a surgeon

Dr Adam Perriman in Bristol on a project which uses 3-D printing to create micro-tumours that start growing in 3-4 days which allows us to investigate which drugs they respond to. We expect that this will have major implications for cost effective personalised medicine in the treatment of cancer.”

A new approach to reduce the impact of ageing For Newcastle University Professor Thomas Zglinicki the biggest challenge that lies ahead for medical researchers is tackling age-related multimorbidity, the incidence of people living with several long-term conditions at a time.

Professor Thomas Zglinicki The professor, who works in the university’s Institute for Cell and Molecular Biology and also Newcastle University’s Institute for Ageing, believes that we stand on the brink of a whole new way of thinking which will reduce the

incidence of age-related chronic diseases such as arthritis, dementia and diabetes.

less drugs and the cost is reduced for the health service.

According to research conducted by the King’s Fund, fifteen million people in England alone have a chronic condition, which is most prevalent in older people; 58% in the over-sixties compared with 14% in the underforties. The research says that the number of people with three or more such conditions is predicted to rise from 1.9 million in 2008 to 2.9 million by 2018.

“It is a new way of thinking in treating humans. What we are seeing now is the developments of drugs that can postpone the onset of these conditions together by slowing down the ageing process.

Professor Zglinicki said: “What tends to happen is that these diseases come as a package. One follows another. You get to 85 and you have four or five conditions. “Realistically, we are not going to cure all these diseases but we can reduce their onset so that someone may get to 85 and only have two conditions, which means they are taking


“One way of doing this is better lifestyles but for many people the idea of a drug that can slow down the onset of chronic conditions may be more acceptable. “This approach offers great potential and is important as populations get older and older. Life expectancy is extending every year. “I am convinced that in a few years from now we will have the first drug that effectively slow down the effects of ageing and delays the onset of age-related diseases, disability and frailty. ”



Hope in the treatment of kidney disease Research into kidney disease is offering hope for sufferers in the years to come.

Another new scientific study gives hope to people suffering from cystinuria, a rare form of kidney stones. The disease is hereditary and if left untreated can lead to kidney failure. The research project saw Dr Hannah Rhodes, a Kidney Research UK fellow, and Professor Richard Coward, of Bristol University, collaborate with Dr John Sayer, Senior Clinical Lecturer in Nephrology at Newcastle University. The team studied the genetic information from a large number of patients who had been diagnosed with the disease.

One piece of research by a Kidney Research UK-funded scientist has made some vital advances in helping to understand a virus which can cause kidney transplants to fail. The work was carried out by Dr Andrew Macdonald, Associate Professor in Virology, and his colleagues at the University of Leeds’ School of Molecular and Cellular Biology and Astbury Centre for Structural Biology. BK polyomavirus infects approximately 90% of all adults without any noticeable effects. However, infection with BK is associated with significant damage to kidney transplants in up to 10% of renal transplant patients. There are currently no treatments targeting BK virus directly so it is seen as a pressing need to better understand the basic biology of this virus in order to find new targets for therapy. In collaboration with Dr Neil Ranson, a worldleading structural biologist at Leeds, the team used cryo-electron microscopy (cryo-EM) to study the virus frozen at -180ºC and produced the clearest picture of the structure of BK virus to date. Rather than staining or fixing the specimens as many observation techniques do, the highly specialised technique allows for the virus to be frozen and imaged in its natural state.

Dr Andrew Macdonald and Janice Richardson, who has had the virus, pictured at a reception Kidney Research held at the House of Lords Dr Macdonald said: “The structure gave us unprecedented access to the inner workings of this virus and provided new understanding of the architecture of both the viral proteins and genetic material. “Looking forward, a solid understanding of the structure of BK will be a vital resource to guide scientists in their efforts to develop targeted therapies against BK associated disease.” Elaine Davies, Director of Research Operations at Kidney Research UK, said: “This work demonstrates how funding from Kidney Research UK allows researchers to push the boundaries of science, and provide essential building blocks of research that will eventually form the pathway to new treatment for patients.”

Dr Sayer said: “This is a rare but important condition, and information in medical textbooks does not describe this condition accurately. There is a need to understand and treat this patient group better. My longstanding interest in stones means that I have been looking after patients with cystinuria for years and the research means I can help them more specifically.” The research study involved analysing the causes and effects of cystinuria and the severity of the disease in the UK. Patients were studied over a period of two2 years in the North East and South West of the UK. The research showed that the disease is severe and treatments need to be more targeted to prevent stone formation. The recording and monitoring of this genetic information will help to achieve an early diagnosis for future generations who are likely to inherit this disease. The team’s next step is to test the findings in clinical trials.

The structure gave us unprecedented access to the inner workings of this virus and provided new understanding of the architecture of both the viral proteins and genetic material.




Hygiene breakthroughs provide promise of success For Dr Pattanathu Rahman, Director of TeeGene Biotech, a Teesside University spinout venture based at the Wilton Centre in Redcar, some of the biggest breakthroughs in the next few years will involve hygiene research and recycling. The doctor, a senior lecturer at the university with 20 years of research experience in novel biotechnological approaches to bioproduct development, said that TeeGene Biotech is focusing its efforts on three core projects which they feel offer some of the biggest potential within the field of bioscience. The first involves the creation of sustainable and high-performance biosurfactants. The biosurfactant market in Europe is already worth £511 million and is expected to grow to £1.35billion by 2030 and Dr Rahman said: “We have developed unique strains of bacteria which produce biosurfactants which work like soap and help to emulsify different liquids. While most people consider soap an effective way of removing bacteria from their skin, we have flipped this idea on its head by discovering a way to create soap from bacteria. “Unlike, traditional surfactants which are made using synthetic materials, biosurfactants can be manufactured in a laboratory and are fully biodegradable and have minimal impact upon the environment, making them much more economical and efficient.”

Dr Pattanathu Rahman

Biosurfactants have anti-microbial and antiaging properties which make them suitable for biopharmaceuticals, cosmetic products and biotherapeutics. However, they can be utilised in a range of industries including oil recovery, pollution reduction and food processing.

at the side of motorways, with the support of BBSRC CBMNet funding. As vehicles pass along the road, tiny amounts of metal, such as platinum, are emitted through their exhausts and absorbed and stored by verge-side plants at a nano level.

Dr Rahman said: “The levels of purity needed for biosurfactants in the industries in which they are used is extremely high. Because of this, they can be very expensive. However, the unique way in which we manufacture biosurfactants means we are able to scale production to meet the demands of the industry.

Dr Rahman said: “We are researching how these nanoparticles are transported inside the plant body - at a membrane level - so they can be extracted and reused. If our research is successful, important elements, which might otherwise be lost, could be reused and recycled. This could have important implications as this method is much less damaging to the environment than mining or conventional methods of extraction.”

“This makes the process much more economical and cost efficient. It’s a very exciting technology with tremendous potential for applications in a range of industries.” His team is also looking at ways in which high value metals can be extracted from plants

The team’s final project, supported by BBSRC– HVCfP, involves using controlled conditions to grow micro algae, containing high-value materials, which have a high temperature threshold and can then be used in biofuels and soil conditioner.


Dr Rahman said: “Although significant challenges remain in the commercial exploitation of algal routes to high value chemicals, the project has established the viability, in principle, of an integrated biorefinery based upon a hydrothermalenabling technology. “This concept is focused on the deployment of integrated biorefinery in the context of waste water treatment and the project has also established that there is technical viability for the recovery of phosphorus from waste water and the production of lipids that are of value to the biofuels, cosmeceuticals and nutraceutical industries. “As biotechnology develops, the range of different applications for which it can be used is constantly growing. These next few years promise to be very interesting for this particular branch of science.”



Setting up a BioScience Business – Policies and Procedures

This is the final part of our short series on setting up a business in the bioscience sector. Previous articles have looked at intellectual property, the management team and finance. In this article we consider what happens next With your funding in place you can now start to hire staff or place contracts with third party service providers to move your business idea forward. As the numbers of people involved grow however so must your administrative structures. Some things are obvious – hiring staff means running a payroll, sorting out contracts, arranging pensions and so on. It is likely too that as you grow keeping your financial records will become more burdensome. Bookkeeping and HR services can however be outsourced but some policies need to be addressed and managed internally. You will need to look at certain health and safety issues and should set up and practice an evacuation procedure in case of emergency – even if you are in rented premises on the ground floor. You should also consider a policy to report safety concerns regarding your processes or technologies. This should go beyond reporting adverse reactions on your own clinical trials but should also address concerns raised by the literature and third parties. In addition to keeping your staff and customers safe you will also want to keep your data safe. Firstly set up a standard operating procedure (“SOP”) to record and manage innovation. This should cover internally generated ideas and those created by your

contractors. Ensure third parties to whom this is relevant are made aware of the policy and commit to following it. Another useful SOP would be one relating to the use of personal devices at work ( “BYOD”). BYOD policies are designed to ensure that only compatible devices and software are used, that viruses are not transferred and that the company can access company data on an employee’s device where use for company business is permitted. The policy might also cover payment for use of a personal mobile phone on company business and use of the internet during business hours. Generally in a business’ early days personal devices are likely to be heavily used but this should be limited or stopped once the company is decently established. The passing of the General Data Protection Regulation means that this is also a good time to review your SOPS for the protection of personal data. It is also wise to review your cyber security as the business grows and becomes more complex. Other common SOPS relate to openness in financial dealings. It is now commonplace to have an anti bribery SOP which should be drawn sufficiently closely to require the divulgence and ideally supervisor or more senior approval, of gifts and hospitality. It is

also good practice to have something about the process for hiring close family members or placing work with their businesses if it is to be permitted at all. Particular care should be taken if it is proposed that family members be involved in product testing or other areas where outcomes must not only be clean of any inappropriate bias but must be seen to be clean. Try to design your SOPs at an early stage so that you are trying them out with just a few people then if you have not quite got them right it is fairly easy to make adjustments but do remember to write them in such a way that they can cope as the company grows. Bonaccord is a law firm specialising in the life science sector. We would be delighted to help you draft appropriate SOPS or to provide further guidance on any of the other issues raised by this series of articles.

Bonaccord – UK Life Science Law Firm of the Year 39


Genome editing


offers hope for leukaemia sufferers

The science of gene editing continues to advance with the announcement by researchers from the Wellcome Trust Sanger Institute of a new approach to tackling myeloid leukaemia (AML). The Cambridgeshire-based Trust and its collaborators have adapted a CRISPR gene editing technique to find new therapeutic targets for the condition. In their research, the team identified a large number of genes that could serve as potential targets for anti-AML treatments and showed how the inhibition of one of them, KAT2A, can destroy AML cells without harming nonleukaemic blood cells. AML, which crowds out healthy cells in the bone marrow, develops rapidly and interferes with the bone marrow’s ability to make normal blood cells, leading to dangerous infections and bleeding. Fewer than one in three people survive the cancer. The team sought new ways to treat AML and used CRISPR-Cas9 gene-editing technology to screen cancer cells for their vulnerable points. They refined a CRISPR-Cas9 technique to disrupt all genes in the leukaemia cell genome individually. This allowed them to identify genes whose disruption was harmful to AML cells. Dr Kosuke Yusa, joint project leader from the Sanger Institute, said: “Previous studies showed proof of principle but this is one of the first systematic attempts to identify

the genetic vulnerabilities of AML. We have improved and applied CRISPR-Cas 9 technology to look at what actually kills cells. CRISPR is becoming a powerful technique in cancer research because it overcomes some of the limitations of earlier tools.” The human genome contains about 20,000 genes but by refining CRISPR-Cas9 technology and using it to screen the leukaemia genome the team uncovered about 500 genes that are essential for cancer cell survival, including more than 200 for which drugs could be designed. They say that, whilst a handful of these genes including DOT1L, BCL2 and MEN1 are already established therapeutic targets, most of them are novel and open up many new possibilities for developing effective treatments against the disease. Dr Konstantinos Tzelepis, a first author on the paper from the Sanger Institute, said: “This is an exciting finding, as KAT2A inhibition worked on a number of primary AML cells with diverse genotypes. Whilst the gene needs to be studied in greater depth to understand its potential for use in the clinic, we show that targeting KAT2A destroyed AML cells in the laboratory while sparing healthy blood cells.”


The team validated this finding, by disrupting the KAT2A gene from leukaemia cells in transgenic mice and observing the effect on the cancer. They found that the mice lived longer when the KAT2A gene was disrupted. Dr George Vassiliou, joint project leader from the Sanger Institute and Consultant Haematologist at Cambridge University Hospitals NHS Trust, said: “This research has led to the identification of many potential gene targets for future AML therapy, which we are making available to other researchers to explore. “Whilst KAT2A inhibition now needs to be investigated as a treatment strategy for acute myeloid leukaemia, there are many more candidates to pursue by the leukaemia research community. Our hope is that this work will lead to more effective treatments against AML that will improve both the survival and the quality of life of patients.” The work was supported by the Kay Kendall Leukaemia Fund, which was established in 1984 under the will of James Sainsbury CBE and awards grants for research on aspects of leukaemia and related haematological malignancies.






Research deepens understanding of genes

Central to effective gene therapies is understanding the way genes work and a new yeast study has suggested that a third of them are involved in metabolism. Metabolism is the biochemical processes that occur inside a cell to maintain life. It includes the breakdown of nutrients to provide energy and produce small molecules such as sugars, amino acids, fatty acids and vitamins, as well as the use of the energy to create the proteins and other molecules the cell needs to carry out its functions. Scientists at the Francis Crick Institute and the University of Cambridge have grown 5,000 strains of yeast, each missing a different gene, to find out what role each one plays. The work led to the discovery that a third of genes are involved in metabolism. The researchers used the findings to create a map of gene functions for yeast genes for which function was previously unknown. Yeast cells have about 6,000 genes, compared with about 20,000 in humans. Prior to this study, scientists did not know the exact role of many of the genes in either species. First author of the study Michael Mülleder was responsible for growing the 5,000 yeast strains

that lacked one gene each, called ‘deletion strains’. He then used mass spectrometry - an analytical technique that allowed him to determine whether there were any differences in the content of amino acids between each strain of yeast. Dr Mülleder of the Francis Crick Institute and the University of Cambridge, said: “Amino acids are very crucial components for metabolism, so the cells need to make sure that they are taken up, broken down or made in the right quantities. That’s why we thought that by measuring them in all of the accessible yeast gene-deletion strains, we would reveal the set of mechanisms that control metabolism.” Dr Markus Ralser, who led the work at the Crick and Cambridge, says: “We found that a third of the missing genes impacted amino acid metabolism, many of them strongly. This is much higher than anyone expected. “We know of no other biological process that requires as many genes to function. Obviously, metabolism played a fundamental role in shaping the way our biologically systems


work. It seems the genome is basically structured around it. “Amino acids play a crucial role in our diet, are implicated in metabolic diseases such as diabetes, and their imbalance causes several rare clinical conditions. Knowing more about how cells deal with them will eventually improve the way we treat these conditions. Further, it will allow us to refine dietary recommendations, perhaps even to tailor them to individuals based on their genetic information.” The scientists will now work on improving the technology so that they can address other parts of metabolism, such as those linked to sugars and fatty acids. They say that because many yeast genes have human counterparts that also have unknown functions, identifying yeast gene functions can help us understand what human genes do. This, they say, can be the first step towards drugs or therapies for conditions that result when genes go wrong.

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