Chain florey 2016 brochure by MRC London Institute of Medical Sciences

First row, left to right: Dr Amit Adlakha, Dr Julie Glanville, Dr Antonio de Marvao Second row, left to right: Dr Pratheeban Nambyiah, Dr Ceris Owen, Dr James Tomlinson Third row, left to right: Dr Jocelyn Walbridge, Dr James Ware, Dr Jennet Williams

Sir Ernst Boris Chain (1906-1979) Biochemist and co-recipient of the 1945 Nobel Prize for Physiology or Medicine for his work on Penicillin. (Image courtesy of Professor Benjamin Chain)

CHAIN-FLOREY Clinical Research Scheme MRC Clinical Sciences Centre

3 Introduction 4

Dr Julie Glanville Dr Antonio de Marvao Dr James Tomlinson Dr James Ware

Foundation Year 2

Sponsors and Advocates Professor Sir John Savill Professor Dame Sally Davies Professor Jonathan Weber Professor Sir Keith Peters Professor Sir Robert Lechler Professor Robert Souhami Professor Dame Kay Davies Professor Sir Andrew McMichael Professor Chris Bunce Professor Sir Stephen Oâ&#x20AC;&#x2122;Rahilly Professor Benjamin Chain

30 Lecturers

Scheme Details

20 Fellows Dr Jocelyn Walbridge Dr Ceris Owen Dr Amit Adlakha Dr Pratheeban Nambyiah Dr Jennet Williams

Dr Harry Leitch Dr Wilson To Dr Phil Ostrowski

42 Alumni

Dr Allifia Abbas Newsholme Dr Tomoki Arichi Dr Parvin Begum Dr Jonathan Bond Dr Elizabeth Byrne Dr Andrew Innes Dr Harpreet Lota Dr Thomas Oates Dr Amit Patel Dr Eleanor Sandhu Dr Philip Webster Dr Jess Zhao

INTRODUCTION medical world. From the first miraculous demonstrations of the life-saving potential of penicillin in mice in May 1940, Ernst Chain and Howard Florey worked tirelessly to optimise its production, saving millions of human lives.Their achievements were recognised in 1945, when they shared the Nobel Prize in Physiology or Medicine with Alexander Fleming. It is in celebration of this unique collaboration that the Chain-Florey Clinical Research Scheme is named. Antibiotics – perhaps the most important 20th Century drug discovery – stand as a tribute to the importance of the culmination of scientific endeavour and medical purpose. In previous decades, the relationship between science and medicine was arguably more transparent. This scheme reignites that longstanding collaborative tradition and provides medical graduates with the opportunity to undertake cutting edge fundamental research. It was founded to spur the development of the next generation of world-class academic clinicians in the UK.

PROFESSOR AMANDA FISHER Director, MRC Clinical Sciences Centre, Imperial College London

The Chain-Florey Scheme brings medical graduates into the basic science laboratories of the MRC Clinical Sciences Centre (CSC) at Imperial College. The scheme is jointly funded by the MRC and NIHR through the Imperial Biomedical Research Centre.

In 1940, Howard Florey, Professor of Pathology at the University of Oxford, elevated penicillin from scientific curiosity to medical revolution. The collaboration between Florey and the biochemist Ernst Chain, supported by the practical knowledge of Norman Heatley, resulted in the isolation and first medical application of an antibiotic. Against the backdrop of World War II, Chain and Florey worked in a makeshift lab on a shoestring budget to unravel the secrets of penicillin.

Since the scheme’s inception in 2009, 18 Fellowships have been awarded and graduates have emerged ready to tackle clinical research questions with scientific precision. Chain-Florey Lectureships allow academic clinicians to go even further. The first Lectureship was awarded in 2014, and 4 Lecturers are now in place. Our new Foundation Year 2 Programme allows exceptional clinical trainees to undertake four months of research in a CSC laboratory. Close mentoring on both the clinical and scientific side ensures Fellows, Lecturers and Trainees keep in touch with their medical roots. Awardees are allowed the time and space to develop the skills they need to bridge the boundary between the clinic and the lab, and to drive medical science forward.

Alexander Fleming had stumbled upon the antibiotic potential of penicillin a decade earlier, with no inkling that his serendipitous discovery would lay the foundation for one of the most important medical advances of the 20th Century. Its power was harnessed long after Fleming had abandoned the project. At a time when hundreds of lives were being lost every day, and a simple scratch could open the door to fatal infection, the combined expertise of a clinically trained pathologist and a biochemist changed the

SPONSORS and ADVOCATES PROFESSOR SIR JOHN SAVILL

Chief Executive, Medical Research Council

“The Chain-Florey Scheme provides a fantastic opportunity for clinical Fellows and Lecturers to work with outstanding basic biomedical scientists at the MRC Clinical Sciences Centre. A key focus for the MRC is to ensure that we are developing clinical academic leaders for the future who are grounded in excellent science, which they can link to their own clinical expertise. Such clinicians will play a critical role in developing knowledge and in ensuring translation of research findings into clinical situations.

“We are developing clinical academic leaders for the future.”

The MRC Clinical Sciences Centre is a unique discovery science laboratory embedded in Imperial College at the Hammersmith Hospital campus. This site has a long tradition of excellence in training clinicians in research and fostering cross-disciplinary collaborations. I and many of my colleagues have benefited enormously from the opportunities offered here. This scheme does a fine job of providing support for clinicians to gain robust scientific training while retaining relationships with their clinical mentors. There are many challenges in ensuring that both sides of this equation are delivered effectively and I am delighted with the success of this scheme in this regard. The Chain-Florey Scheme is a tribute to Professor Fisher, her team and of course to the Fellows, Lecturers and Trainees who have embarked on this challenging but exciting course – it is a real pleasure to read their profiles, which reflect their commitment and enthusiasm – I wish them and all their successors well.”

Sponsors and Advocates

PROFESSOR DAME SALLY DAVIES Chief Medical Officer for England

“Advances in medical practice are powered by cell and molecular biological research. Innovative medicines are reliant on fluent communication between scientists and doctors, and I am in full support of any scheme that fosters such collaboration. The training that the Chain-Florey Scheme provides in the basic science laboratories of the CSC will give them the perfect foundation to build careers that bridge the medical and scientific worlds.

“This scheme is a shining example of the sort of career-shaping programme we are in need of.”

Keeping a firm grip on their clinical work while adapting to the novel challenges of academic life is challenging. I am strongly in support of mentorship schemes for young medical professionals, and this one is paving the way for great futures. The CSC is ideally located at the Hammersmith Hospital, and the clinical mentorship ensures that while Trainees, Fellows and Lecturers grow as scientists, their clinical skills do not wane. Translational research in this country is an absolute priority, so fostering the links between the academics and practitioners of public health is vital. The Chain-Florey Fellows and Lecturers are developing strong relationships with world-class biomedical researchers, and those bonds will last throughout their careers. Training our brightest clinicians in the art of fundamental science will be productive for practical medicine and biomedical science. This scheme is a shining example of the sort of careershaping programme we are in need of.”

Sponsors and Advocates

PROFESSOR JONATHAN WEBER

Director, Imperial NIHR Biomedical Research Centre

“I am a tremendous enthusiast of the Chain-Florey Scheme. Clinician scientists are in short supply, and are a very difficult group to train. With these posts, we agreed from the very beginning that they’d have to be held in a non-clinical lab, but that there would be a clinical mentor to bridge the divide. The Fellows would need strong mentoring, but with the right support it would be an extremely productive programme. The Clinical Sciences Centre is the jewel in the crown for Imperial College in terms of fundamental discovery biology, and we’re delighted to have this landmark scheme there.We’re now using the Chain-Florey model as a template for many other schemes.

“We’re now using the Chain-Florey model as a template for many other schemes.”

The advantage of the scheme is that clinicians and scientists learn to communicate. That communication is bilateral and durable. It can last a whole career, and is the key to this sharp end of translational medicine. This experience will give Fellows not only the skills, but also the tools to ask fundamental questions about clinical issues in the most rigorous way. The next step for the Chain-Florey Fellows is for us to be able to support the most successful in their post-doctoral careers, where the restrictions of clinical training challenge time for research. I am therefore delighted by the creation of the Chain-Florey Lectureships which will guarantee the research career progression of our most able Fellows.”

Sponsors and Advocates

PROFESSOR SIR KEITH PETERS

Senior Consultant in Research and Development, GlaxoSmithKline Emeritus Regius Professor of Physic, University of Cambridge

Clinical research is not for everybody, according to Professor Peters. In fact, he describes it as “a minority taste.” With very few Chain-Florey style programmes in the UK, he says clinician scientists are much sought after. “They are a rare, but necessary, cadre of people: for teaching, to enable science in healthcare, and for the biotech and pharmaceutical industry - where they are valued because they understand scientific methodology as well as medicine.”

“High hopes for Chain-Florey alumnis: ultimately it’s this cadre of people who become the leaders of the profession.”

Professor Peters describes medicine as a very incomplete subject. “There are an awful lot of questions we don’t know the answers to, and people with curiosity want to be in the business of helping to provide those answers.” “The people who are going to make the in-roads are the ones who can pick the problems that are tractable. Physician scientists can do that because they understand that disease is not homogeneous, and they also understand what you can and cannot do with clinical research. An awful lot can be done in mice, flies and worms, but ultimately the research has got to be done on humans.” He has high hopes for Chain-Florey alumni. “Ultimately it’s this cadre of people who become the leaders of the profession. They need to have experience, in a very high quality environment, of being surrounded by those whose business all day and every day is to do research.”

Sponsors and Advocates

PROFESSOR SIR ROBERT LECHLER

Professor of Immunology, Dean, School of Medicine, King’s College London President,The Academy of Medical Sciences

Asked about the key characteristics of a successful ChainFlorey applicant, Professor Lechler is clear. First, he says, the scheme requires a serious commitment to research and discovery, as opposed to just a desire to advance your career and thinking a PhD will help. And a second requirement is “a willingness to take a risk”. This, Professor Lechler says, is because it’s a characterbuilding experience: “As a junior doctor you’re actually quite a responsible person, people listen to you and follow your instructions. You go into a laboratory when you know next to nothing and you feel a bit of an idiot.”

“Chain-Floreys will become role models, and they should themselves champion this sort of approach to help to create look-alike schemes.”

All of which he sees as hugely valuable, because it helps to inculcate modesty and to dispel certainty, which he describes as a dangerous thing. “The Chain-Florey Scheme is a really good exemplar. I don’t think that its alumni are going to change the world on their own, but they will become role models, and they should themselves champion this sort of approach to help to create look-alike schemes.” “I’m very committed to fostering the careers of clinician scientists to help to create an ecosystem that has a mixture of non-clinical basic scientists and clinician scientists working together in an academic medical centre where you’ve got the opportunity for clinical pull as well as discovery push.”

Sponsors and Advocates

PROFESSOR ROBERT SOUHAMI

Foreign Secretary,The Academy of Medical Sciences Emeritus Professor of Medicine, University College London

Professor Souhami fully supports the inspiration that comes from the original scientists at the heart of the ChainFlorey scheme. “Chain and Florey saw what Fleming had shown, and knew that this was something killing bacteria. Something in the petri dish had extraordinary importance biologically and potentially therapeutically. These days an equally important finding might arise from within a randomised trial.”

“The Chain-Florey Scheme is excellent because it sets out to train young clinical researchers within the nature and ambience of world-class molecular biology.”

As an example he cites therapeutic trials in cardiovascular disease, and the incidental finding that in patients given aspirin, the likelihood of colorectal cancer was considerably diminished. Equally interesting was that in those taking aspirin who went on to develop cancer, it was less likely to have spread. “That is an extraordinary finding. Now what is the molecular basis of that? The clinical finding is telling you something very important biologically.” It’s essential, he says, that clinicians interested in research think about, and have an understanding of, basic biology and that molecular biologists are aware of new clinical findings. “The Chain-Florey Scheme is excellent because it sets out to train young clinical researchers within the nature and ambience of world-class molecular biology. They are in a critical environment, where they share setbacks and advances with the scientists and understand what new techniques might offer within clinical research” He sees other benefits too. “At the CSC, scientists are selected from among the very best nationally and internationally, which means that a young clinical scientist can think broadly and seize opportunities.”

Sponsors and Advocates

PROFESSOR DAME KAY DAVIES

Director, MRC Functional Genomics Unit,

Dr Lee’s Professor of Anatomy, University of Oxford

“I’ve always worked very closely at the interface between science and the clinic, and I don’t think that would be possible without having clinical training fellows in the lab. When you get to the translational part of research, it’s a completely different way of thinking. That’s why the links between the clinician at the bedside, the basic scientist in the lab, and the clinical fellows in between is very important indeed.

“This is a very exciting scheme, and incredibly important.”

A gap develops when basic scientists work on a problem in isolation, with no feeling for patients’ needs. You need a full understanding of the clinical phenotype before you can design a research strategy. A clinically trained person adds a tremendous amount. They bring with them a breadth of knowledge about the whole body that simply doesn’t exist without them. Of course, many of them have no idea of the basic science, so it really is an exciting two-way process. Some of them take to it like a duck to water, but not all. But they’re consistently very bright and highly motivated, so they more than make up for it. If you’re trying to practise and do research, you need a clinic within running distance, as it is at the Hammersmith. The Chain-Florey Scheme is ideally placed to promote and support these Fellows. Now more than ever, it’s a challenge for a clinician to take time off during their career. But being in a lab broadens their outlook tremendously. This is a very exciting scheme, and incredibly important.”

Sponsors and Advocates

PROFESSOR SIR ANDREW McMICHAEL

Professor of Molecular Medicine, University of Oxford

“This scheme is very attractive and I have great admiration for the Fellows and Lecturers. They’re doing the sort of things I’ve done in science, but at a far more advanced stage in their clinical training. They will emerge highly qualified both as scientists and clinicians, and there’s always a need for more of those people. When I first went into a non-clinical institution, it was fairly accidental. It was good to be able to concentrate entirely on learning how to do research without having to worry about going to clinics and ward rounds. Now clinical training has become much more formalised, and it can be hard to meet all the requirements to keep your clinical career on track and carry on your work as a scientist. However, this kind of scheme makes it possible.

“If you’re really going to advance translational medicine, these are the people who will be the leaders.”

Getting people started on this career path gives them choices. If you’re really going to advance translational medicine, these are the people who will be the leaders. They are mature, highly motivated, and learn very quickly. They have skills that are very useful for practising as a scientist, but have respect for the full time clinicians dealing with patients. Being able to appreciate their difficulties is very important. My father was a Professor of Medicine at Hammersmith Hospital, so I grew up there. I’ve seen it develop, and with this top class research centre – the CSC – in the grounds it is a fantastic place to work. This whole scheme is excellent, and I wish all the Fellows and Lecturers good luck.”

Sponsors and Advocates

PROFESSOR CHRIS BUNCE

Professor of Translational Cancer Biology, University of Birmingham

“Schemes like the Chain-Florey programme are essential in promoting translational research and addressing the cultural and language barriers between medicine and basic science. This initiative recognises that basic and clinical scientists often need some kind of encouragement to make contact with each other. Translational research has never been so strong. Today it’s possible for non-clinical and clinically trained researchers to build teams, make discoveries and personally drive them all the way to early-phase trials. It feels a bit like a ‘perfect storm’. In the past, translational research was viewed as perhaps not the highest of academic pursuits. Today the ethos across academia and industry is changing. Universities are being assessed not on publication prowess alone, but impact, the extent to which their research actually changes something. The pharmaceutical industry used to translate basic research. Today there is more of a desire to move the risk-taking into academic institutions, which empowers the whole movement towards translational medicine.

“It exposes talented, motivated, well-trained individuals to state-ofthe-art technologies.”

Science is developing at such a great pace and the technologies that are evolving alongside are challenging. If the power of those technologies is not understood within the clinical community, there is a danger that the gap between basic and clinical science will open up again. The whole concept of a scheme like this is that it exposes talented, motivated, well-trained individuals to state-of-the-art technologies. This removes the fear of these technologies and empowers clinicians to embrace the possibilities so that they can be as at home in a lab as they are in a ward.This is really exciting.”

Sponsors and Advocates

PROFESSOR SIR STEPHEN O’RAHILLY

Director, University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit

“I have benefited enormously from working in an environment where basic and clinical scientists rub shoulders with each other on a day-to-day basis. It really helps to foster crossdisciplinary thinking. It can bring to basic scientists clinical perspectives they may not have. The rigour and technologically innovative aspects of contemporary science can enlighten the clinician, who may not have previously appreciated what was possible.

“The raw brain power of many of the young doctors attracted to research training is pretty formidable.”

Some inquisitive and smart doctors have gone into science early after training in medicine and stopped practicing. Several such people such as Mike Brown, Joe Goldstein and Harold Varmus have won Nobel Prizes. What we have now is the opportunity to create a cadre of doctors whose science continues to be driven forward by their active clinical practice. The challenge is to retain clinical credibility and skills in a time of changing knowledge and pressures, while remaining at the scientific cutting-edge. The Hammersmith Campus has been a Mecca for clinical science for many decades.What it’s done very well over the past 10 or 20 years is to strengthen fundamental science, ensuring it doesn’t lose links with the hospital.The raw brain power of many of the young doctors that are attracted to undertake a period of research training is pretty formidable. When you combine that with some of the best scientists in Britain, then that’s a recipe for new ventures and points of light. This is the kind of environment that the MRC Clinical Sciences Centre and the broader Imperial College campus can provide.”

Sponsors and Advocates

PROFESSOR BENJAMIN CHAIN

Professor of Immunology, University College London

“I once met the doctor who administered the first injections of penicillin, when he was a very old man. He said it was the most exciting moment of his life. He had a patient who he knew for sure would be dead by the next morning. He gave him this stuff, and the next day the patient was sitting up in bed, chatting. At that time, the link between scientists and doctors was so close. The barrier has only emerged relatively recently. The Chain-Florey Scheme is breaking down a wall that was never there before.

“My father would have been very supportive of this scheme.”

My father felt very strongly that, in principle, it was very important to have close links between the clinic and lab. He thought that a lot of scientific discoveries of medical importance had come from medical observations. This scheme is something that he would definitely have been in favour of. He spent a lot of time saying that for the vast amount of progress in scientific understanding that he saw, the actual practical medical impact was relatively limited. It wasn’t translated, and it wasn’t clear how it could be. He felt doctors were important for showing scientists the implications for the medical world. He would have been very supportive of this scheme. My father and Florey were an early example of a very successful multidisciplinary approach. The medical profession is very resistant to change, while scientists constantly want to change things. These Fellowships bridge that divide between the conservative and progressive attitude, and get somewhere in between.”

SCHEME DETAILS The Chain-Florey Clinical Training Scheme offers worldclass research training to medical graduates at key stages of their careers. The scheme covers the whole range of clinical training with trainee positions at academic foundation year 2 level, Fellowships at specialist training level and Lectureships once specalist training is completed. Mentoring is key to the scheme’s success: Fellows have two academic mentors and an additional clinical mentor. Lecturers have two mentors, one external to the CSC and one internal mentor. “Working away in a basic science environment, it could be easy for the Fellows and Lecturers to lose track of their clinical training and future careers,” says Professor Charles Pusey, Professor of Medicine at Imperial College and one of the scheme’s advisors. “Fellows and Lecturers find it helpful and reassuring to speak to an independent and experienced clinician who understands the clinical academic career path.” “The Fellows have to learn a totally different way of thinking,” adds Professor Irene Roberts, Weatherall Institute of Molecular Medicine. “They have to employ tremendously different skills to those that make you a successful clinician. The best part of being a mentor is seeing that change in them over time. ”

The Chain-Florey Scheme combines clinical training with world-class fundamental science training. Mentoring is a vital part of its success.

“Clinical mentoring is vital for all clinical academics and especially for the Chain-Florey Scheme where the trainee will be undertaking research in a basic science laboratory. Talking with a mentor can be particularly helpful for Fellows as they start their programme and need to adapt to the steep learning curve of academic training. Later, mentors also help with making decisions about their career trajectory and provide independent support and advice”, says Professor Waljit Dhillo, Professor of Endocrinology at Imperial College. “In addition to a clinical mentor, each Fellow has two CSCbased academic mentors who are experts in the Fellow’s research area”, explains Dr Mark Ungless, Director of Postgraduate Studies at the CSC. “This adds an extra level of support, that is particularly valuable for the Fellows who will find themselves in a very different work environment, with many new challenges, and much to learn”.

Advisors to the Chain-Florey Scheme, clockwise from left: Professor Charles Pusey Professor Waljit Dhillo Professor Irene Roberts Dr Mark Ungless

Scheme Details

CHAIN-FLOREY FOUNDATION YEAR 2 (FY2) TRAINING

CHAIN-FLOREY CLINICAL LECTURESHIPS

The Chain-Florey Foundation Year 2 (FY2) Programme is a collaboration with the North West Thames Foundation School and attracts exceptional clinicians during their academic foundation years to the CSC. The scheme allows clinical trainees in their second foundation year who have completed their PhD and have a strong publication record to undertake four months of research in a CSC laboratory. The CSC provides salary funding and consumables during their research stay. The stay is designed to support a future application for Academic Clinical Fellowships.

Chain-Florey Clinical Lectureships provide support for clinician scientists who have already successfully completed a PhD or post-doctoral fellowship in basic science. The 2-year Lecturerships have been awarded since 2014 in renal medicine, cardiovascular sciences, endocrinology and metabolism and haematology. Funding is provided for the Lecturer’s salary, a consumables allocation and a technician.

Eligibility criteria - Clinical trainee in academic foundation year 2 - Completed PhD - Strong publication record

Eligibility criteria - Clinician scientist - Hold a PhD or post-doctoral fellowship in basic science

CHAIN-FLOREY CLINICAL RESEARCH FELLOWSHIPS Chain-Florey Clinical Research Fellowships are for medical graduates pursuing a career as an academic clinician during their specialist training. Fellows carry out 3 years of PhD research in one of the MRC Clinical Sciences Centre’s worldleading basic science groups. Chain-Florey projects must involve human tissues or samples or be otherwise related to human disease of relevance to the Academic Health Science Centre strategy. Fellows have 3 years to complete their PhD before returning to their postgraduate clinical training. Funding is provided for salary and consumables. Eligibility criteria - NHS Doctor in Training in the UK - Hold a National Training Number and be eligible for ‘OOPE’ (Out of Programme Clinical Experience for Postgraduate Doctors in training) - Would normally have passed Membership exams

For further information: http://csc.mrc.ac.uk/study-here/ chain-florey-clinical-research-scheme/

Scheme Details

CURRENT CHAIN-FLOREYS

â&#x20AC;&#x153;I think changing my way of thinking is going to be interesting. And for me, everything thatâ&#x20AC;&#x2122;s potentially challenging is also a positive thing.â&#x20AC;?

Fellows

DR JOCELYN WALBRIDGE • 2016 Fellow, Meiosis Group

A senior registrar often working shifts, you might think there’s never a dull moment for Jocelyn Walbridge. In the morning, she may rush into emergency surgery to help an expectant mother and her baby, before discussing the long-term care of a woman with cancer in the afternoon. But despite this drama, Walbridge is now looking forward to a new challenge.

yet know exactly where in the conveyer belt this happens, or what triggers it. Walbridge thinks that a ring-shaped complex of proteins, called cohesin, may play a role. This is because cohesin’s activity is affected by the genetic mutation that makes the worms develop tumours. Cohesin normally helps to control the way that cells transmit and express the information in our genes.Walbridge will study its role in developing egg cells, and how this links to cancer.

“Medicine can sometimes feel a bit restrictive. With the intensity and time pressure of the clinical day, you don’t necessarily have time to think around things,” says Walbridge. Now she wants to explore the root causes of ovarian cancer, which until now she has encountered only in terms of diagnoses and treatment plans. In October, she’ll join the CSC’s Meiosis group and begin her research under the supervision of group head, Enrique (Fadri) Martinez-Perez.

She says the ultimate goal of her research is to develop better treatments for her patients. “As a gynaecologist who’s interested in oncology, I’m lucky to have found a project looking at some really fundamental science which could eventually have implications for my clinical practice,” says Walbridge. She will be the first obstetrics and gynaecology clinician to join the CSC on the Chain-Florey Scheme. “It’s slightly out on a limb, and I rather like that.”

Walbridge will focus on a rare type of ovarian cancer, called ovarian germ cell tumours. These tumours originate in a woman’s egg cells, though scientists don’t understand exactly how or why this happens. It’s difficult to study in people, so Walbridge will use the nematode worm Caenorhabditis elegans as a model system. Some of these worms carry a genetic mutation that makes them grow tumours in their developing eggs. Similar mutations can be found in people, and play a role in Cornelia de Lange syndrome, a developmental disorder in which people have a greater than normal risk of cancer.

Walbridge says she’s excited to begin her research and to have the intellectual freedom to ask questions and pursue interesting lines of thought. “I’m a little bit nervous about knowing so little in comparison to everybody around me, but that’s also what’s exciting,” says Walbridge. “I think changing my way of thinking is going to be interesting. And for me, everything that’s potentially challenging is also a positive thing.”

Inside the worms, early egg cells grow and develop in part of a process called meiosis. This happens continuously along a sort-of biological ‘conveyor belt’. However, in worms with the genetic mutation, the cells cannot enter meiosis and instead grow uncontrollably and become cancerous. Scientists don’t

â&#x20AC;&#x153;Iâ&#x20AC;&#x2122;d like to go in that place between the very hard scientific research and looking to try and develop novel therapies, particularly for cancer.â&#x20AC;?

Fellows

DR CERIS OWEN • 2016 Fellow, Lymphocyte Development Group

“It’s very interesting to try to unpick what the changes are that lead from normal cell function, to cancer cells. If you can understand these changes, then that potentially leads to interventions to block some of them, and stop the cells from becoming cancerous,” says Owen.

The childhood cancer, Wilm’s tumour, mostly affects those younger than five. It grows in the kidneys and was the focus of Ceris Owen’s early investigations as a research graduate. In a cancer laboratory based in Bristol, Owen and colleagues looked at a receptor that sits on the surface of kidney cells. They found that the genes which are used to produce these receptors are turned off, or ‘silenced’, in Wilm’s tumour. According to Owen, it’s now known that the same silencing can occur in cancers that affect adults, such as colorectal cancer.

Owen says it’s important for clinicians to have an understanding of how medicines can develop from an initial idea, through basic research, into clinical trials and on to become a drug that’s used to treat patients. “In fact, ultimately, the kind of work I’d like to do is to go in that place between the very hard scientific research, and looking to try to develop novel therapies, particularly for cancer,” says Owen.

In the ten years since his initial research, Owen has stepped away from the laboratory and trained as a physician, specialising in clinical genetics. Now a Registrar at St George’s Hospital, London, he focuses on patients with inherited cancers. This year he will return to his research roots when he joins the CSC as a Chain-Florey Fellow to explore cancer at the cellular level.

Traditional chemotherapy drugs target all fast growing cells, but can kill healthy cells too, and often cause distressing side effects such as ulcers, immunosuppression and hair loss. “The aim now is to look at each cancer individually and say, well, what cell type does this come from, what are the mechanisms by which this cancer is reliant for turning over rapidly, and how can we target specific treatments for this specific cancer,” says Owen. “The aim is to individualise treatments and minimise side effects.”

Owen says he feels a bit nervous because he’s had such a long break from laboratory work. “It’ll take me a little bit of time to find my feet, but hopefully it’s still in there somewhere and the techniques are still there, and thinking about things in a more scientific way will still be there too. We’ll see!” He will join the Lymphocyte Development group, supervised by CSC director Amanda Fisher. Owen says he’s interested in exploring the signals sent inside a cell that trigger it to make copies of its genetic information, and to divide to create ‘daughter’ cells. By understanding how this happens in healthy cells, he aims to better understand how it can go wrong and make some cells divide uncontrollably, ultimately developing into cancer.

Fellows

“I’m learning techniques that I’d only read about when I was in medical school.”

Fellows

DR AMIT ADLAKHA • 2014 Fellow, Computational Regulatory Genomics Group

Genes drive many of the cell’s activities, so looking at gene expression in this way will help to clarify the impact of the drugs, and ultimately how this prevents the immune system from fighting off the fungal infection.

A lung transplant can save patients’ lives. But if a patient’s immune system recognises the new organ as foreign, it may attack and destroy it. Drugs called calcineurin inhibitors suppress the immune system, but these same drugs increase susceptibility to a deadly infection with the fungus Aspergillus fumigatus.

“We’re not aiming to change the drugs that are used to prevent rejection. It’s more to see if there are other ways, other immune-based treatments, that might boost the fungus-killing effects of the immune cells themselves, whilst the patient is on the drugs,” says Amit. This could eventually reduce the number of transplant patients who die from fungal infections, but such a treatment is a long way off.

“It’s a key cause of death within the first year after lung transplantation. Nine in ten patients who contract it will die, despite appropriate anti-fungal treatment,” says Dr Amit Adlakha. Scientists do not yet fully know how calcineurin inhibitors put patients at risk, which is the subject of Amit’s Chain-Florey Fellowship.

Amit is in the final year of his Fellowship. “There is a real sense of completion in going through the whole work-flow – from taking blood, to differentiating cells in the lab, to then performing computational analysis on the sequencing data.” But he admits that it’s been a steep learning curve. “I’m performing techniques that I’d only read about when I was in medical school. It’s great to be actually doing them.”

Amit takes blood samples from healthy volunteers and patients, and extracts immune cells from the samples. He then exposes the cells to calcineurin inhibitors and infects the cells with Aspergillus fumigatus. This way he can analyse how the drugs affect the way that the infected cells mature, function and fight off the infection, compared to controls.

He finds the pace of science is also very different to the hospital ward. “Often in a hospital environment, we can’t plan very far in advance, but respond to things happening in front of us. The Fellowship has been really good for teaching me to think ahead.”

Amit is also investigating how the immune-suppressing drugs affect which genes are turned on, or ‘expressed’, in the cells. When a particular gene is expressed, the cell produces messenger molecules that carry instructions from that gene to other parts of the cell. Amit extracts these molecules and uses computer software to track how their levels change over time, to find out when certain genes are expressed.

Fellows

“One of the great things about being here is that it’s really opened my mind to the fact that so many aspects of science interact and fertilise each other.”

Fellows

DR PRATHEEBAN NAMBYIAH • 2014 Fellow, Behavioural Genomics Group nervous system.” Studying an organism with a short lifespan allows Pratheeban to investigate questions he can’t answer with human studies because of confounding external factors and ethical concerns.

“If you’d asked me before I started this PhD, I would’ve had a very restrictive idea about what is acceptable research pertaining to paediatric anaesthesia. But one of the great things about being here is that it’s really opened my mind to the fact that so many aspects of science interact and fertilise each other.”

“There’s a definite culture shock as a doctor coming to research. It’s a very different environment, particularly basic science research. Scientists think very differently, they discuss differently, the way they ask questions is quite different.” As a clinician, Pratheeban finds his days are very busy, and handson. There’s little time to think about the future, and speculate on how to advance his speciality. But he finds a great sense of satisfaction from counting off the number of patients seen and operations done.“Research is different. It requires a much greater degree of motivation in many respects, because you don’t have that instant satisfaction at the end of each day. You do have a lot more time to think and plan, and then write and ask questions. But certainly if you’re new to it, it’s not so easy to use that time efficiently, and I think that’s one of the skills that scientists build up.”

Born in Sri Lanka, Pratheeban Nambyiah spent a few years of his childhood living in South America before his family moved to East London. He finished his specialist training in anaesthetics last year, and worked as a local consultant at Great Ormond Street Hospital. “I came to do this PhD to explore some of the actions of anaesthetics that we don’t think about quite so much in day-to-day practice. Generally speaking, people think about an anaesthetic as something that puts them to sleep and keeps them asleep, and then once they’re awake everything’s back to normal- that’s how we’ve thought about it for many years. The analogy is like being on an aeroplane flight: everyone’s aware that there’s a certain level of risk while you’re taking off, while you’re in the air, and while you’re landing, but then when it’s done it’s done. But now there’s more and more evidence that anaesthetics might have longer term actions and effects that persist beyond the actual episode of the anaesthetic itself.”

Pratheeban is an unusual Chain-Florey Fellow in that he’s starting his academic career at a relatively late stage, most doctors who pursue a PhD will do it before their medical training is finished. But Pratheeban feels there is an advantage to waiting: “I know now what I want to do with my career, and I’m able to match that to my research interests. It’s great to find something else that challenges you and pushes you that bit further.”

Pratheeban is doing his research in Andre Brown’s Behavioural Genomics Group using the nematode worm C. elegans as a model organism to match behaviours with genetics. “I can expose these worms to anaesthetics, and then look for subtle changes in behaviour long after the obvious effect of the anaesthetic is worn off. If I can show these subtle changes of behaviour, then I can look further to see what might have changed within the functional architecture of that worm’s

Fellows

“It’s incredibly challenging, but do-able!”

Fellows

DR JENNET WILLIAMS • 2013 Fellow, Cellular Stress Group

may well do different things in different types of cancer or at different stages in the disease.”

“As a Medical oncologist you’re familiar with reading about and interpreting Western blots but when you actually do your own for the first time it feels like a really big achievement,” says Jennet Williams, who started her Chain-Florey Fellowship in March 2013.

Having completed one fellowship already at The Wellcome Trust Centre for Human Genetics in Oxford, Jennet was no stranger to the lab. “The Chain-Florey Fellowship has provided an excellent opportunity for me to combine basic science training with my interest in cancer metabolism, while continuing to work as a clinician” she says. One of the biggest challenges of the Fellowship has been adapting from being one of the most experienced people in her job as a Medical oncology Registrar, to the least experienced person in the lab – and therefore being dependent on other people. But she enjoys lab work and hopes to continue her current line of research.

Jennet studied medicine in Wales. Caring for cancer patients as a Palliative Care Registrar in Bristol, she developed a desire to specialise in Medical oncology. During her Academic Clinical Fellowship at Imperial College London she heard about the Chain-Florey scheme. Jennet now works in the Cellular Stress Group under Dave Carling, whose research aims to understand the regulation and roles of AMP-activated protein kinase (AMPK), a key governor of energy metabolism. She is fascinated by a phenomenon known as the Warburg effect – the observation that cancer cells metabolise glucose differently to normal cells. Although first discovered in the 1920s, the significance of the Warburg effect was neglected until very recently, when ‘reprogrammed energy metabolism’ was added to the original six hallmarks of cancer. Given the key role that AMPK plays in metabolism and the metabolic changes that occur in tumours, AMPK is likely to be important in cancer so she’s looking specifically at the effects of activating AMPK in the liver during the development and progression of liver cancer.

“You know the work you’re doing in the lab is going to generate results, and whether positive or negative, they’ll answer questions. Cancer research is evolving rapidly and much of the progress made has been at the basic science level. As a specialty, Medical oncology really lends itself to a career as a clinician scientist. It’s incredibly challenging, but do-able.” Jennet has already got results and some of her findings have been surprising. “Our model hasn’t behaved as we expected it to, given what we know about AMPK, but that’s exciting – it suggests things are more complex than we originally thought and that there’s more to investigate.”

“If AMPK inhibits cancer, then you could use drugs that activate AMPK in patients with hepatocellular cancer so that there is more AMPK around in the liver cells. This could slow tumour growth,” explains Jennet. “But the evidence as to whether AMPK is a friend or foe to cancer is conflicting. It

DR JULIE GLANVILLE • 2015 Clinical Lecturer “This has been a challenging year” Dr Julie Glanville admits, “establishing a lab is full of new hurdles. The tissue culture is now up and running, and the Chain-Florey Scheme provides a research assistant which is invaluable.”

“The idea is to develop some of the ideas from my PhD into optimising T-cells for adoptive therapy, but at a really basic science level which is where the CSC platform excels.”

Julie’s path towards becoming a Chain-Florey Lecturer began when she was still an undergraduate student in Cambridge. “I loved immunology right from the beginning. David Weatherall helped me to organize an elective in Vietnam. Out there, I was fascinated by the interplay of the immune system and tropical diseases. I met a haematologist who inspired me: haematology is such a unique specialty, and it allows me to bring together my love for immunology, tropical medicine, adventurous places

Lecturers

and great science.” Julie trained as a haematologist in London and spent nine months in Africa setting up a MSc course and haematology service. “I had always enjoyed bone marrow transplantation and adoptive T-cell therapy, and when I came back from Africa, I wanted to specialize in T-cells. I went to Oxford to do a DPhil with Andrew McMichael. I was very interested in how you can use T-cells therapeutically to treat viral infections post transplantation, and target T-cells to attack the leukaemia. Over the last few years technology has been developed where the T-cell is engineered to express a chimeric antigen receptor (CAR) that targets B-cells. The results are impressive.”

“Institutes that integrate medicine and science are rare in the UK. It’s a great challenge as these are two specialties in their own right with their own languages. That’s the benefit of the Chain-Florey Scheme.”

The field of adoptive T-cell therapy – transferring improved immune cells into a patient – is relatively new, and ripe with opportunities for junior researchers. “I am trying to develop some of the ideas from my PhD to optimize T-cells for adoptive therapy. This is at a basic science level which is where the CSC platform excels.” Julie believes that the integration of medicine and basic science enriches both fields. “Institutes that integrate medicine and science are rare in the UK- these are two specialties in their own right with their own languages. That’s the benefit of the Chain-Florey Scheme but it’s also a great challenge. This year I have had to think about how to set up the infrastructure to work on human T-cells. Now I can study the signaling molecules we’ve identified and see if these enhance killing, and if the epigenetic state impacts function. Practicing medicine puts you in the path of great people needing cures, and this can open new directions in science”. “The opportunity to look at things differently, to stop and think about the practice of medicine are some of the luxuries that the Chain-Florey programme provides.”

Lecturers

DR ANTONIO DE MARVAO • 2015 Clinical Lecturer

Antonio is a cardiologist. He’s trying to understand the factors in our genetic make-up and in our environment that influence the shape of our hearts and how they function, both when we’re healthy and when things go wrong.

“The Chain-Florey Scheme is so special because it allows you to just keep going – with research and clinical training in tandem.”

“During my first 3 years, as a Chain-Florey Fellow, I focussed on finding a better way to phenotype the heart.We developed a new Magnetic Resonance Imaging (MRI) technique that allows us to image the heart in 3D, thereby acquiring a huge amount of information about the organ in one go.” Antonio worked with colleagues to develop a computer programme that automatically analyses these high-resolution images, by measuring the heart at 46,000 individual points. The current standard is just a couple. They recruited some

Lecturers

2,000 healthy volunteers, scanned their hearts and gathered data on their genetic sequences, levels of physical activity, smoking and past medical history.

“Once I have developed credible foundations in clinical practice and science I hope to influence health and medical sciences’ policy and drive improvement in patient care.”

This novel method was first applied in a study of the effects of blood pressure. “We know that people with very high blood pressure develop typical changes in the heart…the muscle walls get much thicker. With standard imaging of the heart we are only able to detect those with severe disease. However, using our high-resolution models we found that these changes start much earlier, even in people with normal blood pressure.” The next step is to combine all the information they’ve amassed to try to work out the specific genetic variants that influence heart function and shape across a healthy population.

trainee. Then your academic development is assessed using criteria such as publications in high impact journals, securing your own funding and demonstrating research excellence in your field, despite the ever increasing pressure to provide clinical services.”

“We’re also studying NHS patients with diseases of the heart muscle, or cardiomyopathies. Using advanced statistical modelling we are trying to find which genes and which specific characteristics in their heart scans better predict how well they’re going to do in the longer term.”

“Having a research project closely aligned with your clinical interest helps to improve your productivity. Securing a clinical Lectureship at an institution such as Imperial College, where I’m in daily contact with so many successful and inspirational senior clinical academics is a fantastic training opportunity.”

Antonio views the clinical lectureships as unique because there are so few opportunities like this that provide time to dedicate to research. “Normally this period after the PhD is the hardest, and the time that most people fail on their academic progression, because you don’t have enough research under your belt to set up on your own, and you have to finish your clinical training. The Chain-Florey scheme is so special because it allows you to just keep going – with research and clinical training in tandem.”

And in the long term? “I aim to continue as a clinical academic, to look after patients and from them gain inspiration to lead my own bedside-to-bench-to-bedside programme in translational research.” Though his overarching scientific goal is to define the genes and biological pathways that lead to heart disease, he has other goals too. “Once I have developed credible foundations in clinical practice and science I hope to influence health and medical sciences’ policy and drive improvement in patient care.”

He finds combining clinical and academic training extremely demanding, but thinks tensions between the two lines of work may prove good preparation, because clinical academics need excellent time management. “On the clinical side you have to acquire all the skills and knowledge expected from a full time

Lecturers

DR JAMES TOMLINSON • 2015 Clinical Lecturer

“To develop a novel drug, that would be the ultimate aim – the gold star,” says Dr James Tomlinson, of his research on chronic kidney disease.

“To develop a novel drug, that would be the ultimate aim – the gold star.”

Kidney disease can increase your risk of having a heart attack or stroke, and some people are more susceptible to it than others, though scientists don’t yet fully understand why. It’s also difficult to study the disease in people because it can be caused by a variety of factors, such as environmental stresses, illness and genetics. It’s also tricky to pin point the precise onset because kidney damage builds up over time.

Lecturers

But James has an eloquent solution. He plans to study patients who receive kidney transplants at Hammersmith Hospital. Although the procedure ultimately helps patients recover from kidney disease, it can also damage the kidney that’s being donated because the new kidney has been out of the body and deprived of a blood supply for many hours. James will be able to identify exactly when this damage begins and track the progress of individual patients from this point onwards.

DDAH1 is the nasty culprit and you have to reign it right in. It’s more that the background level of DDAH1 is not a good thing in people who suffer an injury,” says James. The ultimate goal is to develop a drug to inhibit DDAH1, but this is a long way off. Scientists first need to understand its role in our kidneys’ cells. James uses mice and rats to investigate its function, and his early results are promising. “We have some data that show it’s very specific to a certain cell type in the kidney, within the proximal tubules.”

The Hammersmith campus is an ideal location for the research. “The population of patients with kidney conditions here is massive. The numbers coming through are high for kidney transplants, chronic kidney disease and many other types of kidney conditions,” says James.

Of course, the Lectureship is not without its challenges. “The transition period – switching between the lab and clinic – can be difficult. One moment your pipetting clear fluids and then the next you’re going off to do various clinical procedures on the wards. It’s difficult to make that mental switch,” says James.

He also explores the extent to which the long-term health of the transplanted kidney is affected by the genes within the kidney itself, which come from the donor, and the genes in the tissues that surround it, which come from the recipient. A gene that encodes an enzyme, called DDAH1, is of particular interest. There are many versions of this gene and some put you at greater risk of developing chronic kidney disease.

“It’s not necessarily that DDAH1 is the nasty culprit and you have to reign it right in.”

By comparing genes in the transplanted kidney with the recipient’s genes, James can explore how different versions of DDAH1 contribute to an individual’s risk of developing fibrosis, and ultimately chronic kidney disease. But the exact role of DDAH1 is not clear.“It has been thought that DDAH1 in the blood vessels is a good thing, because it lowers blood pressure and so helps to keep us healthy,” says James. “But we’re not convinced that it’s necessarily as simple as that, because in the kidney, the same version of the enzyme can make fibrosis worse.” Fibrosis is scarring of the kidney, and usually occurs following an injury or illness, such as diabetes. “It’s not necessarily that

Lecturers

DR JAMES WARE • 2016 Clinical Lecturer

Picture a heart that is ‘baggy’ and stretched on one side. Its thin muscle is too weak to pump blood around the body. This disease, called dilated cardiomyopathy, affects 1 in 250 people and can lead to sudden death. Earlier diagnosis may help to save lives.

“We can use this information to screen patients’ relatives to identify those at risk of developing the disease, and help them to manage their condition early.”

Cardiologist James Ware seeks to understand the genetics of the disease. James is sponsored by the Wellcome Trust and has joined the CSC as a Chain-Florey Lecturer equivalent. He is also a group head at the Imperial College National Heart & Lung Institute and consultant cardiologist at Royal Brompton

Lecturers

Hospital, and works with Professor Stuart Cook, who leads the CSC’s Cardiovascular Magnetic Resonance Imaging and Genetics research group.

facilities in Hammersmith Hospital, the first place in the world to have a commercial MRI scanner. “We also hope to carry on with our gene discovery projects, particularly early onset childhood dilated cardiomyopathy,” said Ware. If scientists can find out more about titin, they may one day be able to develop new ways to treat dilated cardiomyopathy.

The pair first worked together in 2008, when James completed his PhD at the CSC. He went on to post-doctoral research at the CSC, Imperial College, Harvard Medical School, and the Broad Institute. James is exploring computational methods for genome interpretation, with a particular focus on inherited cardiac conditions, and gene discovery in patients with unexplained cardiomyopathies. “We are also studying a large cohort of healthy volunteers who have had cardiac MRI and gene sequencing at the CSC, looking for genetic determinants of heart structure and function,” James said. Dilated cardiomyopathy can be caused by mutations in a gene that produces a protein called titin. It is the largest protein in the human body, and acts like a spring within muscle tissue, including the heart. Many patients with dilated cardiomyopathy have DNA mutations in the Titin gene, that disrupt formation of the Titin protein. But about 1 in 100 people have similar mutations and remain healthy. “That really threw a spanner in the works,” said Ware. By examining the differences between the two groups, he’s been able to work out why some mutations cause disease, and others don’t. “We can use this information to screen patients’ relatives to identify those at risk of developing the disease, and help them to manage their condition early,” explains James. Together with Stuart Cook, he is now finding out more about the role of titin in the healthy heart by creating 3D images using the cutting-edge magnetic resonance imaging (MRI)

Foundation Year 2

DR HARRY LEITCH • 2015

DR WILSON TO • 2015

Foundation Year 2 Trainee

Dr Harry Leitch came to the CSC from Cambridge where he held a position as an academic foundation trainee. At the CSC, Harry worked with Petra Hajkova in the Reprogramming and Chromatin group where he has been studying epigenetic reprogramming in the mouse germline. He has been using a range of techniques - from cell and organ culture, next generation sequencing techniques to mass spectrometry. The FY2 programme allowed him to set up experimental systems and to generate preliminary data which he hopes will fuel a successful academic clinical fellowship.

Dr Wilson To gained his PhD in Physiology in Birmingham before completing clinical school. He then joined North Central Thames as an academic foundation trainee. Being awarded an FY2 position under the Chain-Florey scheme, Wilson worked with Amanda Fisher’s group on developing and utilising a new generation imaging system to study epigenetic change. The FY2 programme provided him with an opportunity to explore an area of science that he believes will be influential in shaping patients’ care in the future. “The experience and contacts have been invaluable”, Wilson says about his time at the CSC.

Harry will be staying at Imperial NHS Trust and the CSC for an Academical Clinical Fellowship in paediatrics.

Wilson will be an Urology Academic Clinical Fellow at the London Deanery.

Foundation Year 2

DR PHIL OSTROWSKI • 2016 Foundation Year 2 Trainee

Having previously completed his FY1 year at the Royal Surrey County Hospital in Guildford, Dr Phil Ostrowski is now working as an FY2 trainee with Prof Stuart Cook and Dr Declan O’Regan, looking into myocardial structure and function in healthy volunteers and subjects with mutations of the titin (TTN) gene. The group has a large cohort of subjects who have had both detailed genomic studies and cardiac MRI scans. Phil uses a variety of commercial and in-house software to interpret the imaging studies and to look for links between genetic variability and cardiac phenotype. “The most enjoyable element of my work at the CSC is having a clearly defined translational aspect to my research”, Phil says. Phil will move on to Core Medical Training at the Royal Brompton Hospital and Chelsea and Westminster Hospital.

Foundation Year 2

CHAIN-FLOREY ALUMNI 41

Alumni

DR ALLIFIA ABBAS NEWSHOLME • 2011-2015

DR TOMOKI ARICHI • 2009-2012

“Learning the language of science has been a real eyeopener,” says Dr Allifia Abbas Newsholme. Her PhD project involved developing a system to image gene expression changes in real time. The system will be useful for looking at how environmental factors influence changes in gene expression during pregnancy. “It’s an uncomfortable thing to unfetter yourself from your clinical preoccupations,” Allifia says, as she reflects on her Fellowship. But now she has the confidence of a clinician, able to “talk the language of science.”

Since completing his Fellowship, Dr Tomoko Arichi remains committed to clinical academia, and was appointed an NIHR Clinical Lecturer at King’s College London in 2012. This post has given him the funds and time to build on the MRI work he started during his PhD and has led to the award of a Starter grant by the Academy of Medical Sciences in 2014. The experience gained in Imaging Sciences at the CSC was vital to his fundamental understanding of the techniques required for this work. Currently he is developing functional MRI techniques to study activity in the developing brain of infants born prematurely and affected by stroke.Tomoki also holds a visiting position in the Bioengineering Department at Imperial College, where they are developing new robotic tools for assessing infant motor function.

Allifia is currently a Renal Registrar at Canterbury Hospital.

Tomoki is currently a Clinical Lecturer in Paediatric Neurology at King’s College London.

Alumni

DR PARVIN BEGUM • 2012-2015

DR JONATHAN BOND • 2009-2012

“The best thing about the Chain-Florey Fellowship is having the time to concentrate on research, not having to do research on the side of your day-to-day work”, says Dr Parvin Begum. Her interest in genetics and epigenetics brought her to the CSC’s Epigenetics section, where she worked with Niall Dillon’s Gene Regulation and Chromatin Group. In her PhD project, Parvin investigated the role of the mitotic kinase Aurora B in lung cancer. “Cancer patients with tumours that overexpress Aurora B have a poor prognosis compared to those who don’t but we know little about the mechanisms underlying this.”

“The chemotherapy used for leukaemia treatment hasn’t changed much in the last 40 years,” explains Dr Jonathan Bond – the first ever Chain-Florey Fellow. “I’m looking at very immature leukaemia cells to understand why normal blood cell development gets blocked and causes leukaemia.” Jonathan is particularly interested in the role of the Core Binding Factor (CBF) protein in these immature leukaemias. “Around 20% of myeloid leukaemias have abnormalities in CBF,” he explains, “so I’m currently exploring how genetic abnormalities in this transcription factor affect early blood cell development.”

Parvin has continued her respiratory specialist registrar training in the London Deanery South program, with a post at King College NHS Trust.

Jonathan works in Elizabeth Macintyre’s lab at l’Hôpital NeckerEnfants Malades Paris supported by a Kay Kendall Leukaemia Fund Intermediate Research Fellowship.

Alumni

DR ELIZABETH BYRNE • 2012-2015

DR ANDREW INNES • 2012-2015

Dr Elizabeth Byrne looked at the changes that occur in Schwann cells after nerve injury. Elizabeth developed a method for separating the Schwann cells from the rest of the nerve in order to look at the RNA expression levels. The results showed differences in gene expression between the Schwann cells from injured and uninjured nerves. This may prove key in our understanding of peripheral nerve repair. Elizabeth’s time in Simona Parrinello’s lab has helped her realize what she wants from a career in the future; she has learnt many translational skills which she feels will be useful in her role as a histopathologist.

Dr Andrew Innes spent his time as a Chain-Florey Fellow studying the molecular mechanisms of senescence – the biological ageing of cells - which plays an important role in understanding and preventing the development of cancer. “The approaches used during my PhD such as RNA sequencing and genome editing with CRISPR technology are key tools in research, and experience with these will improve my understanding of other research as well as being useful techniques going forward into a postdoc project.” His advice for current and future Fellows: “Learn from the others in your lab and don’t be reticent to ask!”

Elizabeth has recently submitted her MPhil and is about to return to her role as a histopathologist at Northwick Park hospital. She plans to apply for a subspeciality training in neuropathology.

Andrew is a Sub-Specialty Trainee in Haematopoietic Stem Cell Transplantation within the Imperial College NHS Trust based at Hammersmith Hospital.

Alumni

DR HARPREET LOTA • 2013-2015

DR THOMAS OATES • 2010-2013

Dr Thomas Oates has no doubt that the three years spent in research has added to his clinical practice. “I feel more able to take an analytical approach to clinical questions based on my scientific training.” During his PhD, Thomas looked at single base resolution analysis of DNA methylation in crescentic glomerulonephritis using bioinformatic methods. “This now means I can tackle clinical projects with much greater ease than previously. Genomic technologies and analysis are seen as a key part of the future of medicine, and my first hand insight into this fast-expanding topic will be extremely useful in appraising the introduction of these techniques into the NHS.”

“I’ve always wanted to understand the underlying mechanisms of the diseases that as a doctor I have been coming across daily”, explains Dr Harpreet Lota about her motivation to join the Chain-Florey Scheme. Her research on fibrotic lung disease was connected to her time as a respiratory registrar at the Royal Brompton Hospital. Her early experimental findings formed the basis of a targeted genetic study investigating the association between single nucleotide polymorphisms, longitudinal lung function decline and survival in a well-phenotyped cohort of patients with idiopathic pulmonary fibrosis. Her time as a ChainFlorey Fellow has been an invaluable foundation for future translational research.

Thomas is currently an NIHR Clinical Lecturer in Nephrology & Transplantation at the University College London Centre for Nephrology.

Harpreet will be moving back to clinical medicine to complete her training in 2017.

Alumni

DR AMIT PATEL • 2010-2013

DR ELEANOR SANDHU • 2012-2015 What makes salt so attractive that some patients cannot stick to a medically required low-salt diet? During her Fellowship, Dr Eleanor Sandhu worked with Mark Ungless (Neurophysiology) and Dominic Withers (Metabolic Signalling) to investigate the networks involved in regulating salt appetite. Her work was inspired by dialysis patients on a low-salt diet with whom she had worked as a doctor. “I’ve been very lucky that I’ve had the freedom to create my own project”, she adds. Eleanor hopes that there might be help for dialysis and heart failure patients if research can uncover a way to reduce their salt appetite through some form of manipulation.

Dr Amit Patel completed his PhD in 2013 under Luis Aragon. He used yeast as a model system of DNA damage and repair. He found that a DNA double strand break during telophase is repaired using homologous recombination despite segregation of sister chromatids, making repair inherently mutagenic. This novel discovery has broad implications to cancer formation and relapse after treatment. Amit has since completed clinical academic subspecialty training in stem cell transplantation and intensive care medicine in 2016. He is currently developing cellular immunotherapy for patients with haematology cancers, graft versus host disease, and sepsis.

Since completing her research work, Eleanor has rejoined the London Deanery Renal program to continue her specialist registrar training. She now works as a medical registrar at North Middlesex Hospital.

Amit is a NIHR Clinical Lecturer in Haematology and Intensive Care Medicine at the Institute of Cancer Research, and an Honorary Clinical Lecturer at Imperial College London.

Alumni

DR PHILIP WEBSTER • 2011-2014

DR JESS ZHAO • 2010-2013

“The Chain-Florey Fellowship is an excellent opportunity to acquire solid, basic science training for any doctor intending to have a career in academia,” says Dr Philip Webster, who completed his PhD under Anthony Uren in the Cancer Genomics group. Phil looked at the kinetics and genomics of BCL2 driven lymphoid malignancies, focussing on B cell apoptosis. “I wanted to gain knowledge, experience and learn new techniques within the genomics of the immune system and then apply this to my interest in autoimmune diseases.” Having returned to his speciality training in renal medicine, he intends to pursue an academic career path.

“I would definitely recommend this Fellowship to doctors with an interest in basic science. It provides an excellent opportunity to carry out exciting research supported by experts in their fields.” Dr Jess Zhao completed her PhD research project in the Cellular Stress Group with Dave Carling. “The Chain-Florey Fellowship has given me the opportunity to work in a fantastic lab and has confirmed my desire to become an academic clinician. Finding the right balance of clinical and research work has been more challenging than I expected, and it’s still something I’m working on.” Having returned to complete her core medical training, she hopes to pursue a career in academic medicine in the future, and is particularly interested in specialising in care for the elderly.

Phil is currently a Renal Registrar at Imperial College Healthcare NHS trust and an Academic Clinical Lecturer at the College.

Jess is currently completing GP training in Southampton.

Dr James Tomlinson (2010-2013) and Dr Antonio De Marvao (2012-2015) took up Chain-Florey Lectureships upon completing their Chain-Florey Fellowships.

Image credit: Amanda Fisher by Robert Taylor, www.taylor-photo.co.uk Produced by: Grants, Engagement and Communications Facility, MRC Clinical Sciences Centre. Printed by ScanPlus.

Howard Walter Florey (1898-1968) Pathologist and co-recipient of the 1945 Nobel Prize for Physiology or Medicine for his role in the development of Penicillin. (Image courtesy of the Australian National University)