Ernst Boris Chain

CHAIN-FLOREYClinical Research Fellowships

4 Introduction 12 Fellows

5 Sponsors and AdvocatesProfessor Sir John Savill

Professor Dame Sally Davies

Professor Jonathan Weber

Professor Benjamin Chain

Professor Sir Andrew McMichael

Professor Dame Kay Davies

11 MentorsProfessor Irene Roberts

Professor Charles Pusey

Professor Anne Soutar

Dr Jonathan Bond

Dr Tomoki Arichi

Dr Amit Patel

Dr Jiexin Zhao

Dr James Tomlinson

Dr Thomas Oates

Dr Philip Webster

Dr Eleanor Sandhu

Dr Andrew Innes

Dr Allifia Newsholme

Dr Antonio de Marvao

Dr Elizabeth Byrne

Dr Parvin Begum

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.

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 only 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 medical world. From the first miraculous demonstrations of the life-saving potential of penicillin on mice in May 1940, Ernst Chain and howard Florey worked tirelessly to optimise its production, saving millions of human lives in the process. 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 Fellowships are named. antibiotics – perhaps the most important 20th Century

Chain-Florey Clinical Research Fellowships offer medical graduates PhD opportunities in basic science laboratories at the MRC Clinical Sciences Centre

drug discovery – stand as a tribute to the importance of the culmination of scientific endeavour and medical purpose. the Chain-Florey Fellowship scheme brings medical graduates into the basic science laboratories of the MrC Clinical sciences Centre (CsC) for three-year PhDs.

the scheme is jointly funded by the MrC and nihr through the imperial BrC. Founded to spur the development of the next generation of world-class academic clinicians in the UK, the Chain-Florey Fellowships are an investment in the future of academic medicine. in previous decades, the relationship between science and medicine was arguably more transparent. this Fellowship reignites that longstanding collaborative tradition and provides medical graduates with the opportunity to undertake cutting edge fundamental research. over three years in the CsC at the hammersmith hospital campus, Fellows develop their research skills and become as comfortable in the laboratory as they are on the ward. Close mentoring on both the clinical and scientific side ensures Fellows keep constant touch with their medical roots.

since the scheme’s inception in 2009, 14 Fellowships have been awarded. The first Fellows are now emerging, ready to apply their skills to tackling clinical research questions with scientific precision. The experience affords Fellows the skills required to bridge the boundary between the clinic and lab, and drive medical science forward by studying the basics of health and disease.

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sPonsors & aDvoCatEs

the Chain-Florey scheme provides a fantastic opportunity for clinical Fellows to work with outstanding basic biomedical scientists at the MrC Clinical sciences Centre. a key focus for 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. 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 fellowship is a tribute to Professor Fisher, her team and of course to the Fellows 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.

ProFEssor sir John saviLLChief Executive, Medical Research Council

CHAIN-FLOREYClinical Research Fellowships

“ We are developing clinical academic leaders

for the future ”

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- Sponsors & Advocates -

ProFEssor DaME saLLy DaviEsChief Medical Officer and Chief Scientific Adviser, Department of Health

Cell and molecular biological research powers advances in medical practice. the development of innovative medicine is reliant on fluent communication between scientists and doctors, and i am in full support of any scheme that fosters such collaboration. the training that these Chain-Florey Fellows receive in the basic science laboratories of the CsC will give them the perfect foundation to build careers that bridge the medical and scientific worlds.

For these Fellows, 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 they grow as scientists, the Fellows’ clinical skills don’t 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 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 career-shaping programme we are in need of.

“ This is paving the way for great futures”

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- Sponsors & Advocates -

ProFEssor Jonathan WEBErDirector of Research, Imperial NIHR BRC

“Moving into a non-clinical lab for three years transformed me in terms of my clinical science,” says Professor Jonathan Weber, Director of the imperial nihr BrC, which jointly funds the Chain-Florey Clinical research Fellowships. “i was the only clinician in the building. it was a frightening experience. But to learn the language of science and establish a dialogue with a high level scientist is invaluable, and can only be achieved by this rite of passage.

i am a tremendous enthusiast of this 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.

the advantage of these Fellowships 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.”

“ To learn the language of science is

invaluable ”

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ProFEssor BEnJaMin ChainProfessor of Immunology, UCL

“I once met the doctor who administered the first injections of penicillin, when he was a very old man,” recalls Professor Benjamin Chain, son of Ernst. “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. these Fellowships are breaking down a wall that was never there before.

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.”

“ My father would have been very supportive of this

scheme ”

- Sponsors & Advocates -

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- Sponsors & Advocates -

“ Some of them take to it like a duck to water,

but not all ”

ProFEssor DaME Kay DaviEsDirector, 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,” says Professor Dame Kay Davies. “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.

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, they 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.”

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- Sponsors & Advocates -

ProFEssor sir anDrEW McMiChaELDirector, Weatherall Institute of Molecular Medicine, University of Oxford

“this scheme is very attractive,” says Professor sir andrew McMichael. “i have great admiration for the Fellows. 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.

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. i do a lot of clinically oriented research, so interact with clinicians regularly. 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 good luck.”

“ Getting people started on this career path gives them

choices ”

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ProFEssor irEnE roBErtsProFEssor CharLEs PUsEyProFEssor annE soUtar

“the Fellows have to learn a totally different way of thinking,” says Professor irene roberts. “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 the time of the Fellowship. they all approach it in different ways, but having the best scientific training at this early stage will give them flexibility. that bedrock on which they build their way of thinking about science is vital, no matter what they go on to do.”

“Working away in a very basic science environment, it could be easy for the Fellows to lose track of their clinical training and future careers,” says Professor Charles Pusey, Director of Clinical academic training at imperial College. “having clinical mentors allows the Fellows to discuss their progress and get impartial advice from a senior academic clinician. the success of mentoring depends on the relationship that develops between mentor and mentee. the frequency of meetings is variable, and driven by the Fellows. they generally find it helpful and reassuring to speak to an independent and experienced clinician who understands the clinical academic career path.”

“of course, the Fellows have two academic mentors, as do all PhD students at the CsC, but the clinical mentors are key to the success of this scheme,” agrees Professor anne soutar, Director of Postgraduate studies at the CsC. “the Fellows are in a strange environment, completely out of their comfort zone. When they start it’s an absolute sea change for them. they go from being quite senior and responsible in the clinical arena to the bottom of the laboratory hierarchy. they’re suddenly working in an environment where they’re more expected to solve problems as an individual. having this contact with the clinical world, and with someone who speaks the same language, is extremely important.”

MEntors

CHAIN-FLOREYClinical Research Fellowships

Introduction

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Introduction

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Fellows

Introduction

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“This discovery was a very exciting moment for me,”

said Bond when he hit upon a protein-protein interaction

implicated in leukaemia

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Dr JOnaTHan BOnD • 2009

Fellow, Gene Regulation and Chromatin Group

Dr Jonathan Bond became the first Chain-Florey Fellow in 2009, although he hadn’t originally planned to do basic science. “i was interested in doing research,” he says, “but i saw myself doing something a bit more translational.” a year and a half at the institute of Child health (iCh) in London helped spark his interest in solving clinical problems using scientific methods. “For example, while working at the iCh, i discovered novel genetic mutations in a patient with pulmonary hypertension and erythrocytosis. This identified a novel disease mechanism, and was also very important for the patient’s subsequent treatment. this work triggered my decision to pursue research in a bit more depth, through a basic science PhD at the CsC”.

Jonathan completed his medical training in ireland in 1999, remaining there for a further eight years to qualify as a haematologist. When he started his Fellowship at the CsC in 2009, he hoped his experience at the institute of Child health would help him acclimatise to the lab. “i thought i would hit the ground running…that it would be straightforward. it wasn’t. i don’t think it comes naturally, and it certainly takes a while to adjust to this way of thinking.”

now fully adjusted, he nears the conclusion of his Fellowship and his research is starting to bear fruit. “i’m looking at transcriptional regulation in B cell development. My research focuses on the interplay between two transcription factors – Foxp1 and ikaros.” Building on previous work done in niall Dillon’s lab, which identified a physical interaction between

these factors, Jonathan is investigating the mechanism and functional consequences of this.

“i’ve been looking at how the proteins interact by using co-immunoprecipitation, in vitro assays and cell culture. We’ve explored the functional aspect by overexpressing the proteins to see how the cells respond, and we’ve looked at how these factors bind Dna directly.” His investigations have identified a key link to leukaemia. the transcription factors together interact with a gene which codes for a protein called G2a. this protein is involved in leukaemia patients’ treatment response. “this discovery was a very exciting moment for me,” Jonathan recalls. “it helped link the research back to the clinical side of things. and it was quite serendipitous; none of us knew the gene before.”

Jonathan doesn’t regret making the leap to basic science. “to become a credible clinical scientist, you need to do a basic science PhD at this stage. i don’t think you’d otherwise embrace the scientific rigour and way of thinking.” now at peace with the “occasional disappointments” that come with lab life challenges, Jonathan plans to stay in science. “avenues have opened up because of the work i’ve done here. i’m going to do a postdoc in Paris, working in a similar area, but focussing on t-cells. Ultimately i want to work as a clinician scientist, with a combined clinical and scientific interest in paediatric leukaemia, and hope to continue to use basic science approaches to address key clinical questions.”

Introduction

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a prize-winning undergraduate in neurosciences, Dr tomoki arichi has set his sights on clinical science. “My undergraduate project employed visual experiments to investigate the underlying biophysics of the pathways involved in visual perception.” the link to his current research on functional magnetic resonance imaging (fMri) is clear.

tomoki worked in the Birmingham Children’s hospital, at Great ormond street hospital, and at the Johns hopkins University in Baltimore, led by his interest in neurology and paediatrics. an academic Clinical Fellowship programme introduced him to research at the CsC. after 9 months, a

Dr TOmOkI arICHI • 2009

Fellow, Neonatal Medicine and Cognitive Neuroimaging Groups

“ What’s very exciting about MR imaging is that we can

use it as a tool to understand what’s going on in the

developing, living brain ”

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- Fellows -

Chain-Florey Fellowship was the obvious move. “i’d done the preliminary work and had questions i wanted to look into more deeply.”

the challenging adjustment to the comparatively unstructured daily life of bench research came early. But for Tomoki, this flexibility has been key. His move to science was accompanied by the arrival of his two children, now 4 years and 18 months old. “i can manage my day in a more flexible way. Doing computer-based work at home means I can take my daughter to school.”

Dr arichi works between the neonatal Medicine and Cognitive neuroimaging Groups. “i’m developing and optimising fMri techniques for premature and newborn babies,” he explains. “Babies born prematurely have a high risk of lifetime difficulties with all the different capacities of the brain, such as movement and learning. What’s very exciting about imaging is that we can use it as a tool to understand what’s going on in the developing brain in a completely non-invasive way. it’s a compelling and important field. Were they born 30 years ago, these babies wouldn’t have survived.”

the work has two strands – optimisation of various fMri techniques, and their application. “Getting accurate fMri data from babies has always been a problem, both from the analysis and physics side, and in terms of using the right stimuli for the babies. We’ve been designing and testing tools that might help.” these tools include a device that moves the baby’s hand or wrist, and a technique for presenting different smells to the baby. “and it’s fully automated,” he adds. “in the past, someone might stand in the room and lift the baby’s hand up. But now the stimulus can be very reliable, fully repeatable and carefully controlled.”

tomoki’s work on improving the data acquisition and analysis process has already yielded a published paper. “We’re getting some promising results. We’ve found premature babies have a simpler pattern of activation in their brain than older children. if we move the right wrist of a premature baby, only one side of the brain activates. the pattern of responses is more complex in older children.” tomoki has high hopes for the future. “at the moment we’re still testing things, but i’d really like to be able to apply them in the clinical setting as time goes on.”

t2-weighted Mr brain scan from preterm infant showing an area of activation (red to yellow) identified following movement of the right wrist

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Dr amIT PaTel • 2010

Fellow, Cell Cycle Group

“the whole experience is very different to what i have been used to in practising clinical medicine.” Dr amit Patel received a poster prize for his clinical research work last year, but approached the Chain-Florey Fellowship with little previous practical experience of basic science research. swapping the ward for the wet-lab has presented novel challenges.

amit is experienced within his two specialties, and the transition from this familiar clinical environment to the relatively foreign world of the lab came as a significant culture shock. “i had experience of clinical research, but i’d had little practical exposure to cutting edge fundamental science. it was certainly challenging when i started,” admits amit. “But being at the hammersmith hospital site means there are always people you know that can help you. it’s a perfect set up.”

amit has little time to spare, between the demands of professional and family life. he is widely involved in all aspects of medical education, and was recognised this year as a Local teaching hero by imperial College London for undergraduate teaching at imperial College healthcare nhs trust. he also manages a small medical education company, holds leadership roles for medical professional organisations, and still finds time to entertain his three year-old daughter.

Dr Patel is a specialist registrar in haematology and intensive care medicine on the imperial and Pan-thames

London Deanery schemes. starting his Fellowship in 2010, he elected to pursue a project in the Cell Cycle Group at CsC, run by luis aragon. after finding his feet he started using a yeast model of Dna damage and repair to understand fundamental processes common to many diseases he has treated. “the project i’m pursuing is centred around repair of the most toxic type of Dna damage, where both strands of the Dna duplex are broken just prior to cell division. in a clinical setting such chromosome breakages can occur, for example following exposure to oxygen therapy or medications. Deciphering repair mechanisms and their control helps us understand how damage might be repaired or therapeutically induced during treatment, and provides insights into how cancer might develop. it could therefore lead to new therapeutic targets being identified.”

“having a fundamental look at a major clinical problem is great,” says Dr Patel, excited by the prospect of delving deep into the molecular basis relevant to a broad range of diseases rather than just one in particular. he remains grounded in clinical practice, working on-call once a week. “that maintains the essential connection to patients. it enables you to focus on the ultimate aim of the research, to translate advances in scientific knowledge into improved treatments for patients. It also keeps your clinical skills sharp.” amit plans to continue as a clinical academic on completion of his Fellowship, building on the foundation established here at the CsC. “the Chain-Florey scheme paves the way for you to be as comfortable in the research lab as you are in the hospital.”

Introduction

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“ The Chain-Florey scheme paves the way for you to be as comfortable in the research lab

as you are in the hospital ”

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- Fellows -

“ I can almost see a glimpse of the mechanism I’m looking for. It’s

exhilarating… ”

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Jess Zhao is unfazed by being the youngest Chain-Florey Fellow. at 26 she comes to the scheme relatively early in her career, having completed her two foundation years. “there is no structured route towards academic medicine, and everyone does this at different times in their careers,” she says. “I’m sure I’ll catch up. It’s definitely the right thing for me to be doing now.”

starting her Fellowship in 2010 meant a geographical and professional change. Born in shanghai, Jess moved to edinburgh aged 13 and later completed her medical degree and foundation years in scotland. “London is a massive city. i had doubts about moving here, but i am enjoying it. still getting my head around how long it takes to get anywhere, though. now i’ve got to know people here, i’m not sure if i’ll return to scotland after my Fellowship.”

Jess is no stranger to the lab. “i did a lot of summer student jobs in labs in scotland,” she recalls. “i’d always wanted to integrate research into my medical career.” that goal has been realised, and she is currently working in the Cellular stress Group at the CsC, looking at the basic science of septic shock.

“septic shock arises following an infection,” she explains. “The body produces an inflammatory response. Cytokines and metabolites cause the blood vessels to dilate, and the blood pressure drops dramatically.” her research involves

an investigation into a protein kinase called CaMKK beta. “We stumbled upon quite an exciting finding,” she reveals. “in a cohort of mice where we’ve ‘knocked out’ CaMKK beta, the animals seem to be resistant to septic shock.”

the role of this enzyme in the development of septic shock requires further research. “We need to work out the mechanism underlying the resistance. this involves a huge number of approaches: cell culture, flow cytometry, protein kinase activity assays, animal studies.” the list goes on. “i think i have it narrowed down to the fact that the knockout mice can maintain their blood pressure. if we can translate this into a human treatment,” adds Jess, “it will be very exciting.”

this prospect is far from fantasy. a pharmacological inhibitor of CaMKK beta already exists, so her project has the potential to yield very tangible results. Jess is approaching the end of her Fellowship, and has enjoyed the change in scenery. “Practically and socially, it’s been a very different experience. in a lab you’re with the same group of people all the time, and there is a constant exchange of ideas.” she does not see the end of her PhD as the end of her work, however. “i can almost see a glimpse of the mechanism i’m looking for. it’s exhilarating, but once i get there, that will open up a whole world of different areas to go into. there’s never an end!”

Dr JIexIn ZHaO • 2010

Fellow, Cellular Stress Group

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an undergraduate research project at the William harvey research Institute gave James Tomlinson his first taste of life in the lab. “Once you’ve had a flavour of research early on and enjoyed it, you’re likely to come back to it,” he says.

James graduated from medical school and started on his training programme in London. an entertaining 18 months in australia and new Zealand helped him “get some good clinical experience in a very different environment”. returning to England, he joined a London rotation and then started his renal specialist training in 2008.

James’ Chain-Florey Fellowship began in 2010. “it was a shock to go from being quite able and responsible, relatively

Dr James TOmlInsOn • 2010

Fellow, Nitric Oxide Signalling Group

“ …every small step is a eureka moment... ”

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far down a certain career path, to having no idea at all. you’ve got to be resilient, but the sacrifice is hopefully met with significant gain.” Two years on, Tomlinson is seeing some of those benefits. “Being immersed in the scientific world gives you a deeper appreciation of good and reliable data,” he says. “In the clinical world, you take in new findings and results on a daily basis. Doing this science helps you better understand the limitations of these tests. it’s subtle, but important.”

Tomlinson is looking at the mechanisms of renal fibrosis. “almost any kind of kidney injury from an acute illness or inflammatory disease triggers scarring in the kidney. a bit like with skin, scar tissue distorts the normal architecture, affecting the function of the kidney.” he hopes to elucidate the underlying mechanisms by investigating the role nitric oxide plays in the scarring process. “We’re looking at the pathways that increase or decrease local nitric oxide. the work is mostly in vitro cell culture, using cell lines and tissue from mouse kidney. We also look at how knock-out mice with kidney diseases develop.”

the project focuses on DDah and aDMa – two critical components of the nitric oxide pathway. “the question is how important are these proteins for the progression of renal fibrosis? In theory, there are compounds that we’ve created that could target them so there could be some therapeutic potential there. For a clinician doing research, the link to the patient is important.”

During his Fellowship, dipping his toes into the waters of conference presentation has been a particular highlight for James. “often, you’re working on relatively obscure things, so to find some common ground and have some really progressive conversations is exciting. it’s rewarding and very motivating to speak to people and debate ideas on the spot.”

too engrossed in his ongoing work to yet focus on the future, tomlinson is enjoying the unique satisfaction that science provides. “When you’re embroiled in it, every small step is a eureka moment, and that’s half the fun. in a sea of frustration you get occasional leaps forward, which are hugely satisfying.”

Introduction

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“…my goal is to develop more tailored therapies, and reduce side-effects ”

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Dr THOmas OaTes • 2010

Fellow, Integrative Genomics and Medicine Group

Dr thomas oates was wooed by the intrigue of science during the summer of 2001. “i’ve always felt strongly compelled to do research,” he says. he spent a summer in Paul Greengard’s lab at the rockefeller University, new york, the same year Greengard won the nobel Prize. “they call it ‘big-shot science’,” he smiles, “i was just some 21 year old who got a salary and an apartment. it was great fun. they were all very driven, so it gave me an insight into goal-oriented science.”

renal specialist tom oates started his Chain-Florey Fellowship in september 2010. “i’m far enough down the line with my medical career to know what is useful and interesting for me, and now seemed the best time.” the CsC was an important part of the attraction for oates. “the highest quality research is always going to come from people trained in high quality labs, from the basics upwards.”

the work life of a scientist is not the same as that of a medic. “in medicine the work never stops – it comes to you. When you start in science, the self-start determination is a challenge. the experiments don’t do themselves, choose themselves, or make themselves work. But now i’m used to that, i enjoy it.”

Dr oates works in the integrative Genomics and Medicine Group on glomerulonephritis, an inflammatory disease of the kidneys, predominantly of autoimmune aetiology. “I’m looking at how epigenetic modifications – mostly Dna methylation and histone modifications – play a role

in an animal model’s predisposition to glomerulonephritis.” oates is trying to identify differences in these epigenetic modifications between two rat strains – one that is susceptible to glomerulonephritis and one that is not.

“i started with Dna sequencing experiments. now i’m further into the project and using whole-genome sequencing to look at methylation differences between these two rat strains.” tom’s project looks at the role of macrophages in glomerulonephritis. and his project has the potential for some significant therapeutic developments. “Patients with glomerulonephritis get bombarded with treatment, so the goal is to develop more tailored therapies, and reduce side-effects. Targeting epigenetic modifications would certainly be novel as a therapeutic approach.”

the nature of his research means oates has not only had to hone his lab skills, but his computing abilities too. Previously, he asserts these extended not far beyond reading his emails. now comfortable with programming and computational statistics, oates adds that he, “got a real kick out of learning to properly harness the power of computers and the vast sources of information available.”

Being the only medic in a lab of scientists may have made Oates “the butt of a lot of scientific jokes”, but that’s done nothing to dissuade him from pursuing basic research. “Doing this very basic work provides an excellent grounding, no matter what you go on to do.”

Introduction

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“When you start, it’s a real baptism of fire,” muses Dr Philip Webster, casting his mind 11 months back to when he began his Chain-Florey Fellowship. “i’d spent a little bit of time in a lab before, but there was still plenty of floundering. You come in really knowing nothing. This is one of the hardest thing i’ve done.” and if the challenges of lab life aren’t enough, Webster has a 19-month-old daughter at home, although he finds the flexibility of lab work a boon. “in clinical medicine you’re very constrained,” he explains, “i still work long hours but i’m more in control of my time. My wife is a full time clinician, so now i can work around her if i need to.”

Dr PhiLiP WEBstEr • 2011

Fellow, Cancer Genomics Group

“ If we can find groups of genes that are interacting to produce cancer, we could produce inhibitor drugs to temper these genes, and develop

patient targeted gene therapy ”

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Dr Webster trained in nottingham and has worked all across the country and beyond, including a somewhat traumatic stint in a hospital in the australian outback: “running a hospital single-handed, hundreds of miles from anywhere was awful at the time, but brilliant in hindsight.” in 2007 he came to London, and later began his specialist training as a nephrologist. he simultaneously embarked on an academic Clinical Fellowship, before being accepted to the Chain-Florey scheme in 2011.

With an interest in immune-mediated diseases such as the immunology of organ rejection, Webster was attracted to the Cancer Genomics Group. “Lots of renal diseases are autoimmune,” he explains, “in which the body makes antibodies and literally attacks itself.” treatments squash the immune system with immunosuppressant drugs, although patients are at risk of infections. “Cancer is emerging as a more common cause of death in renal transplant patients,” he reveals, “but there aren’t many people in renal medicine who have done scientific research in oncology. It’s an unfilled niche.”

Webster is looking at the mechanisms of lymphoma – a cancer of the white blood cells that can affect

immunosuppressed patients. his project uses a technique called insertional mutagenesis to inject a retrovirus into newborn mice. insertion into the mouse genome causes mutation of neighbouring genes, which drives lymphoma development. “We identify the regions where the virus genome inserted, then sequence the nearby genes.” in this way the team can identify common insertion sites, before analysing how nearby genes are involved in lymphoma development.

One specific gene, BCL-2, is involved in preventing apoptosis (programmed cell death). if overexpressed, cells persist and proliferate for too long, leading to cancer. By identifying genes that commonly collaborate with BCL-2, Webster will alter their expression in human lymphoma cell lines, to see what role they play in lymphomagenesis. “If we can find groups of genes that are interacting to produce cancer,” he clarifies, “then we could develop patient targeted gene therapy.” Current drug treatments are highly toxic, not always effective, and have not changed for decades.

the research is still nascent, and Webster is cautious but hopeful. “there’s a lot of potential in what we’re doing here.”

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- Fellows -

Eleanor sandhu trained at Cambridge and UCL. as a senior house officer she worked all over london, and she completed a Diploma in tropical Medicine and health in thailand. now her three children are in preschool, Eleanor is taking this opportunity to commit time to research. she opted for basic science over anything more clinical, despite limited prior lab experience. she has no shortage of clinical knowledge and maturity, having almost completed her renal specialist training. a “nephrologist’s obsession” with salt, water, and blood pressure guided her choice of research project, which will deal with intake control in metabolism. analysing reward processes involved in ingestion, the work has a clear link with neurophysiology and neuropsychology. she plans to investigate the response to salt depletion and loading in a mouse model.

Dr eleanOr sanDHU • 2012

since graduating from the University of Dundee, andrew innes has gradually moved south, from preregistration house jobs in Glasgow to senior house officer work in Manchester. in London he completed his specialist registrar training, and was awarded an academic Clinical Fellow post in haematology by the London Deanery. together with his intercalated degree project on the anti-platelet effect of chocolate, andrew has some experience of the laboratory environment. this has cemented his intention to pursue an academic career, and his clinical maturity will help ease the transition. his research project involves developing an in vitro model of cellular senescence to identify the regulating factors, and help clarify the role in physiological ageing, inflammation, fibrotic disease and in graft-versus-host disease following allogeneic stem cell transplantation.

Dr anDreW Innes • 2012

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- Fellows -

in 2002 antonio de Marvao moved from Lisbon to Glasgow to complete his undergraduate medical degree. he remained in scotland for his early postgraduate training before moving to London in 2009. throughout his clinical work, de Marvao has sought to understand the fundamental basis of the diseases and therapies he has been confronted with. now he brings that curiosity to the lab. through his clinical experience as a cardiologist, he frequently encountered patients with inherited cardiac conditions. his research will investigate the genetic basis of these conditions, to help develop techniques to determine disease risk, and to allow for prevention and stratified treatments. The work also aims to generate an mrI-derived 3D atlas of the heart, helping him to map the effects of genetic variants onto ventricular function and morphology.

Dr anTOnIO De marvaO • 2012

allifia newsholme moved from Dubai to leeds to study medicine. she has a degree in infection and Molecular science and has spent time training in new Zealand, and the Uk. scientific research has always been in allifia’s sights, and during an intercalated degree she completed a project based on optimising molecular techniques for detection of Mrsa. she began renal training in 2009, and with her basic medical skills, has a sense of perspective on her research. her project aims to investigate how changes in the in utero environment, such as nutritional conditions, can alter the expression of maternally expressed imprinted genes. these might have a role in developmental programming, and the ultimate incidence of chronic diseases such as type ii diabetes mellitus and hypertension.

Dr allIFIa neWsHOlme • 2012

Dr elIZaBeTH BYrne • 2013

- Fellows -

Parvin Begum is the most recently recruited Chain-Florey Fellow. she graduated from the University of Birmingham in 2007 and spent two years working at University hospital Birmingham. her interest in research led her to take up an nihr academic Clinical Fellowship in London in 2009. Parvin did her core medical training at Guys & st thomas’ hospitals, and was an honorary research Fellow at Kings College London. in 2011 she began her specialist training in respiratory medicine. the prospect of doing research in an institute at the forefront of biomedical research drew Parvin to the CsC, where she starts her Chain-Florey fellowship in late 2012.

Dr ParvIn BeGUm • 2012

Elizabeth Byrne moved from a small village on the outskirts of Manchester into the heart of the city, to complete her medical degree and Bsc in Pathology. she undertook an academic foundation programme in East London before moving to Leeds to begin her histopathology specialist training. she returned to London to take up an academic Clinical Fellowship, and has worked at hammersmith hospital for two years. Elizabeth’s project is not yet confirmed and she approaches the Fellowship with an open mind while she decides on her speciality. she hopes that taking this time to focus on the basic science of one area in depth will equip her with the skills to grapple with both diagnostic and research work in the future.

inside cover image courtesy of Professor Benjamin Chain. inside back image © national Portrait Gallery, London. Edited and designed by anthony Lewis. Photography by richard newton. Public Engagement Media & Grants Facility, MrC Clinical science Centre.

For more information and eligibility details, visit www.csc.mrc.ac.uk/ChainFlorey

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hoWarD WaLtEr FLorEy

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