Chain Florey Brochure 2015

CHAIN-FLOREY Clinical Research Scheme

FELLOWS AND LECTURERS 2015

First row, left to right: Dr Amit Adlakha, Dr Parvin Begum Second row, left to right: Dr Elizabeth Byrne, Dr Julie Glanville Third row, left to right: Dr Harpreet Lota, Dr Antonio de Marvao, Dr Pratheeban Nambyiah, Dr Eleanor Sandhu Fourth row, left to right: Dr James Tomlinson, Dr James Ware, Dr Jennet Williams

CHAIN-FLOREY Clinical Research Scheme Dr Elizabeth Byrne Dr Harpreet Lota Dr Pratheeban Nambyiah Dr Eleanor Sandhu Dr Jennet Williams

2 Introduction 3

Sponsors and Advocates Professor Sir John Savill Professor Dame Sally Davies Professor Jonathan Weber Professor Dame Kay Davies Professor Sir Andrew McMichael Professor Chris Bunce Professor Sir Stephen O’Rahilly Professor Benjamin Chain

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Advisors Professor Charles Pusey Professor Irene Roberts Professor Anne Soutar

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Chain-Florey Scheme Details

13 Fellows Dr Amit Adlakha Dr Parvin Begum

29 Lecturers

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

37 Alumni

Dr Allifia Abbas Newsholme Dr Tomoki Arichi Dr Jonathan Bond Dr Andrew Innes Dr Antonio de Marvao Dr Thomas Oates Dr Amit Patel Dr James Tomlinson Dr Philip Webster Dr Jess Zhao

- Introduction -

The Chain-Florey Fellowship Scheme brings medical graduates into the basic science laboratories of the MRC Clinical Sciences Centre at Imperial College for three-year PhDs. The scheme is jointly funded by the MRC and NIHR through the Imperial Biomedical Research Centre, and 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 (CSC) Head of the Institute of Clinical Sciences, Imperial College London “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.

“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” Since the scheme’s inception in 2009, 17 Fellowships have been awarded and graduates have emerged ready to tackle clinical research questions with scientific precision. ChainFlorey Lectureships allow academic clinicians to go even further. The first Lectureship was awarded in 2014, and 4 Lecturers are now in place. Close mentoring on both the clinical and scientific side ensures Fellows and Lecturers 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 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.

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PROFESSOR SIR JOHN SAVILL Chief Executive, Medical Research Council

CHAIN-FLOREY Clinical Research Scheme

“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 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.

SPONSORS AND ADVOCATES

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 and Lecturers 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.”

“We are developing clinical academic leaders for the future”

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- Sponsors and Advocates -

PROFESSOR DAME SALLY DAVIES Chief Medical Officer and Chief Scientific Adviser, Department of Health

“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 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.

Keeping a firm grip on their clinical work while adapting to the novel challenges of academic life is challenging for these Fellows. 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 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 are developing strong relationships with worldclass 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 and Advocates -

PROFESSOR JONATHAN WEBER Director, NIHR Imperial Biomedical Research Centre

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

“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.

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.”

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- Sponsors and Advocates -

PROFESSOR DAME KAY DAVIES Director, MRC Functional Genomics Unit, Dr Lee’s Professor of Anatomy, University of Oxford

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

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 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. 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. 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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- Sponsors and Advocates -

PROFESSOR CHRIS BUNCE Professor of Translational Cancer Biology, University of Birmingham

“It exposes talented, motivated, well-trained individuals to state-of-the-art technologies” “Schemes like the Chain-Florey Fellowship programme are essential in promoting translational research and addressing the cultural and language barriers between medicine and basic science. This pro-active 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.

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.”

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- 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 cross-disciplinary 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.

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 brainpower 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.”

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

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- Sponsors and Advocates -

PROFESSOR BENJAMIN CHAIN Professor of Immunology, UCL

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

“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.

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.”

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The mentor system of the Chain-Florey scheme is a vital part of its success.

Chain-Florey Advisors explain why it is so important

CHAIN-FLOREY

“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, Professor of Medicine 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.”

Clinical Research Scheme

ADVISORS

“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.”

Professor Anne Soutar Professor Charles Pusey Professor Irene Roberts

“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.”

Dr Mark Ungless becomes Director of Postgraduate Studies at the CSC in 2015, as successor to Professor Soutar.

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- Chain-Florey - Introduction Scheme-Details -

CHAIN-FLOREY CLINICAL FELLOWSHIPS

CHAIN-FLOREY CLINICAL LECTURESHIPS

ELIGIBILITY CRITERIA

RESEARCH AREAS

• NHS Doctor in Training in the UK

• Renal medicine

• Hold a National Training Number and be eligible for ‘OOPE’ (Out of Programme Clinical Experience for Postgraduate Doctors in training)

• Cardiovascular sciences • Endocrinology and metabolism • Haematology

• Would normally have passed Membership exams

Chain-Florey Clinical Research Fellowships are for medical graduates pursuing a career as an academic clinician. Fellows carry out their research in one of the MRC Clinical Sciences Centre’s world-leading 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.

Chain-Florey Clinical Lectureships provide support for clinician scientists who have already successfully completed a PhD or post-doctoral fellowship in basic science. The first Lectureship was awarded in 2014 to Dr James Tomlinson in renal medicine. Additional Lectureships have been awarded in cardiovascular sciences, endocrinology and metabolism and haematology. As a world leader in basic science, the MRC Clinical Sciences Centre strengthens its support for clinical academia through the Lectureship programme.

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

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CHAIN-FLOREY Clinical Research Scheme

FELLOWS 2015

First row, left to right: Dr Amit Adlakha, Dr Parvin Begum Second row, left to right: Dr Elizabeth Byrne, Dr Harpreet Lota Third row, left to right: Dr Pratheeban Nambyiah, Dr Eleanor Sandhu, Dr Jennet Williams

- Introduction - Fellows - -

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

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- Fellows -

DR AMIT ADLAKHA • 2014 Fellow, Computational Regulatory Genomics Group

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.

drugs, and ultimately how this prevents the immune system from fighting off the fungal infection.

“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 affects 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 transplantation. Nine in ten patients who contract it will die,” says Dr Amit Adlakha. Scientists do not yet know exactly how calcineurin inhibitors put patients at risk, which is the subject of Amit’s Chain-Florey Fellowship.

He has just passed the half-way point in his Fellowship. “It’s good fun doing the gene expression experiments because there is a real sense of completion,” says Amit. “It’s nice to go through the whole work flow – from taking blood, to extracting cells in the lab, to analysing data on a computer.

The fact that I am now able to do this from start to finish shows that I’ve learned a lot over the last year and a half.”

Amit takes blood samples from healthy volunteers and patients at Hammersmith Hospital, and extracts immune cells from the samples. He then infects the cells with Aspergillus fumigatus, and treats some of them with calcineurin inhibitors. 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.

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. Now I’m really getting results – not just perfecting my technique.”

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.

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.”

Genes drive many of the cell’s activities, so looking at gene expression in this way will help to clarify the impact of the

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- Introduction - Fellows - -

DR PARVIN BEGUM • 2012 Fellow, Gene Regulation and Chromatin Group

important in cancer,” explains Parvin. She is trying to find out more about the transcriptional regulation of this gene.

“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,” Parvin comments. “I want to look specifically at the epigenetic effects of Aurora B in lung cancer.”

“The best thing about the Chain-Florey Fellowship is having the time to concentrate on a completely new area,” says Dr Parvin Begum, now two years into her PhD with Niall Dillon in the CSC’s Gene Regulation and Chromatin Group. “As a doctor you can do some clinical research on the side of your day-to-day work, but to have robust scientific training in a place like this is a great opportunity.” With an NIHR Clinical Academic Fellowship under her belt, Parvin comes to the Institute with some previous lab experience. “I had a little time in the lab as part of my NIHR Fellowship but it was enough to give me the exposure I needed to consider a basic science PhD rather than a predominantly clinical one.”

Parvin has had to get to grips with lab techniques including cloning, transfection, Western blotting, chromatin immunoprecipitation, RNA analysis and gene reporter assays. “Thanks to my former lab stint, I didn’t feel too uncomfortable at the bench,” she says. “But it’s a completely new venture. There’s a lot to learn. You do some basic science in your medical degree, although nothing this in depth.” During her two years she’s been using mouse cells.

“We had ChipSeq data for that, so I’ve been cloning and modifying parts of the genome that potentially control the Aurora B kinase gene in mouse to see what’s important.

I am now focussing on the human system and starting experiments with lung cancer cells.”

A year’s speciality training in respiratory and general medicine has led to her clinical interest in lung cancer. “I’ve always been interested in genetics, and then started to become really interested in epigenetics. That combination of interests brought me to the CSC at Imperial, because there is such a strong epigenetics section here.” She is investigating the role of a mitotic kinase in lung cancer.

“The kinase is known to be involved in cell cycle regulation, having important functions in mitosis. Recently the lab discovered that Aurora B kinase also plays a role in regulating quiescence.” Quiescence describes a resting state where cells are not actively dividing but retain the ability to re-enter the cell cycle. “It’s important in maintaining tissue homeostasis.”

“It’s fascinating to be able to physically manipulate gene sequences to try to answer questions you’re interested in.”

In the future she hopes to continue with research. “It’s great being at the CSC.There’s so much expertise and technology available if you want to use it.”

Parvin is looking at whether Aurora B may be involved in mediating the choice between cells continuing to cycle or entering quiescence. “Deregulation of that process may be

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“It’s fascinating to be able to physically manipulate gene sequences to try to answer questions you’re interested in”

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- Introduction - Fellows - -

“It’s been a very slow process.

At one point I thought it wasn’t going to work, but now it seems we’re starting to get somewhere!”

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- Fellows -

DR ELIZABETH BYRNE • 2013 Fellow, Cell Interactions and Cancer Group

the levels and diversity of RNA inside Schwann cells after injury she hopes to build up a picture of the molecular changes that result from nerve damage. “I’ve been getting to grips with RNA extraction, which is quite challenging because RNA degrades so quickly.”

After completing an Academic Clinical Fellowship at Imperial College London, Dr Elizabeth Byrne received a tip off from her supervisor about the Chain-Florey scheme. Her previous fellowship focussed on haematological malignancies. “The main goal was to characterise microRNA expression in lymphomas,” she reveals. “We wanted to know whether they could offer prognostic guidance. Lymphomas can be quite difficult to diagnose and treat, but changes in microRNA expression could help to better group patients, offering more targeted treatments and a clearer prognosis.”

In order to isolate the cells Elizabeth is using a mouse model that has red fluorescent Schwann cells. After making a cell suspension, she uses Flourescense-activated cell sorting (FACS) to extract the Schwann cells. At that stage the challenge is to get enough good quality RNA to sequence.

“I’ve got to the point where I can isolate the Schwann cells and get RNA of good quality in sufficient quantities. So I’ve reached a point where we can start sequencing now, which has just happened in the last few weeks.”

Elizabeth was sure she wanted to do something completely different for her PhD at the CSC. With a project looking at Schwann cell de-differentiation she has certainly ticked that box. Now a year into her Chain-Florey Fellowship – with Simona Parrinello (Cell Interactions and Cancer Group) – she is relieved to be getting her first results. “When I first spoke to Simona about the project I thought ‘I should be able to do this in a few months’,” she remembers. “But it’s been a very slow process. At one point I thought it wasn’t going to work, but now it seems we’re starting to get somewhere!”

While Elizabeth is on track with her project, she is also expecting her second child. “I should be back by January of my final year though, and I’ll be working up until 38 weeks if I can!” Once she has completed her project she plans to resume her clinical work in histopathology on a parttime basis to give her enough time to write up. “I think my specialty is quite compatible with a career in basic research.

Histopathology and research go hand in hand. Since you’re looking at changes in different tissues during disease, you naturally want to know more about the underlying molecular process.” Elizabeth has already decided she wants to specialise in neuropathology once she finishes, so her PhD will provide her with a good grounding in this research arena.

Schwann cells surround the axons of peripheral nerves, producing myelin, which helps insulate the nerve fibre to facilitate signal conduction. “When you get an injury to a peripheral nerve, the Schwann cells de-differentiate. They go back into a stem-cell like progenitor state,” explains Elizabeth. She is trying to characterise the repair process from the perspective of the transcriptome. By measuring

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- Introduction - Fellows - -

DR HARPREET LOTA • 2013 Fellow, Nitric Oxide Signalling and Single Molecule Imaging Groups

“I’ve always wanted to do a PhD,” reveals Dr Harpreet Lota, who took up her Chain-Florey Fellowship a year ago under James Leiper (Nitric Oxide Signalling Group) and David Rueda (Single Molecule Imaging Group). “I wanted to understand the underlying pathogenetic mechanisms of the diseases that as a doctor I have been coming across daily.”

Harpreet finished her fourth year as a respiratory registrar at North West Thames after completing her medical degree at Imperial College London.

a normal feature of wound healing, as Harpreet points out, “the process goes wrong in pulmonary fibrosis.”

“I’m working on a human alveolar epithelial cell line, currently using an iNOS (inducible nitric-oxide synthase) inhibitor to manipulate the tail end of the pathway to see if I can alter the EMT process.” The initiative is geared towards finding a therapeutic application down the line.

“Once I’m done with the cell line, I’ll be able to take the work into a mouse model using the well-known bleomycin murine model of pulmonary fibrosis.” The project requires Harpreet to learn many new techniques including PCR, Western blots, mass spectrometry and cell culture. “I’d done a little bit of PCR before, but everything else is new!”

“When I was a respiratory registrar at the Royal Brompton Hospital, I became particularly interested in fibrotic lung disease, which led to a short-term project at the National Heart and Lung Institute (NHLI) looking at single nucleotide polymorphisms in the hypoxia-induced factor 1 alpha (HIF1A) gene in patients with systemic sclerosis.” This first taste of basic science confirmed Harpreet’s desire to pursue opportunities to carry out research. “I came across an advert for the Chain-Florey Fellowship scheme and thought I would apply.”

IPF is a chronic progressive, fibrotic lung disease with no known cure. “We think it starts from an unknown alveolar epithelial cell injury,” explains Harpreet, “which leads to aberrant wound healing.” The disease is characterised by a honeycomb fibrosis of the lungs, which leads to restricted lung function and severely impaired gas exchange. “Patients get very breathless since thickening and scarring reduces the amount of oxygen that can pass into the blood vessels in affected regions of the lung.” While there are some new therapeutic agents that can potentially slow disease progression, there is no known way to reverse the damage once it happens. “And we don’t know anything about how the DDAH/NO pathway operates in EMT,” says Harpreet.

While her project will help to characterise a well-known pathway in a novel context, there is also the possibility of therapeutic benefit for the 3 in 10,000 people that will develop IPF.

Harpreet’s PhD thesis is borne out of her clinical interest.

“I’m trying to identify the mechanistic pathways linking dimethylarginine dimethylaminohydrolase (DDAH) activity to Idiopathic Pulmonary Fibrosis (IPF).” The DDAH enzymes help to mop up the methylarginines that are produced when proteins are naturally degraded in our cells. Recent research has linked increases in DDAH with epithelial cell proliferation. “At the moment, I’m focussing on epithelial to mesenchymal transition (EMT),” explains Harpreet. During EMT epithelial cells take on a fibroblastic phenotype and lay down extracellular matrix. While this is

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- Fellows -

“I’d done a little bit of PCR before, but everything else is new!”

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- Introduction - 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”

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- Fellows -

DR PRATHEEBAN NAMBYIAH • 2014 Fellow, Behavioural Genomics Group It’s early days in the research career of Dr Pratheeban Nambyiah, a paediatric anaesthesiologist and current Chain-Florey Fellow. “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.”

these subtle changes of behaviour, then I can look further to see what might have changed within the functional architecture of that worm’s 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.

“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 hands-on. 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 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 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

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- Introduction - Fellows - -

DR ELEANOR SANDHU • 2012 Fellow, Neurophysiology and Metabolic Signalling Groups

“It’s fun being involved with setting up a new technique and then getting it to work,” says Dr Eleanor Sandhu who is now approaching the end of her Chain-Florey Fellowship.

Working with Mark Ungless (Neurophysiology) and Dominic Withers (Metabolic Signalling), she is investigating what networks are involved in regulating salt appetite. “I’ve been very lucky that I’ve had the freedom to create my own project.” With an undergraduate medical degree from the University of Cambridge and clinical training at UCL, she moved to North Thames to specialise in Nephrology.

Eleanor comes to the CSC with only a little former lab experience.

is probing this region of the brain with a view to uncovering the networks at play in driving salt seeking behaviour. “From the survival point of view, reward pathways have developed in our brain to drive us to get things we need like food, salt and water,” says Eleanor, “so it looks like drugs of addiction hijack the normal reward system.”

Eleanor explains how she is approaching the research. “I induce a salt appetite in mice using a diuretic – furosemide – to make them salt deplete.” The mice then feed on jellies with differing salt concentrations. “Then I can measure their salt appetite and preference.” With mice genetically modified to express Cre in dopamine neurons, Eleanor is using a virus to transfect a light sensitive channel into the dopamine neurons of the VTA. “The Cre-expressing cells then also express the light-sensitive channel. I then embed a fibreoptic into the VTA.” This allows dopamine neurons to be illuminated and stimulated in situ so that their effect on behaviour can be studied.

As a doctor Eleanor has worked with patients who require dialysis because their kidneys no longer work. “People with heart failure salt retain,” she explains. “They should be on a low-salt diet but seem to have an abnormal salt preference making it very difficult for them.” Patients with kidney failure have a similar problem. Regular dialysis relieves these patients of the water, salt and by-products that they are unable to excrete. “But some of them just can’t stick to the low-salt diet,” says Eleanor, “so they drink too much.

The excess fluid can put huge pressure on the circulatory system and heart, and they often end up with pulmonary oedema.”

The optogenetic system has allowed Eleanor to see what happens to salt appetite when dopamine neurons are stimulated. “Interestingly my results went in the opposite direction to that which I expected. Based on the results of the optogenic and pharmogenetic experiments I am now using electrophysiology to test the hypothesis that salt appetite is a withdrawal state with hypoactive dopamine neurons. This is similar to alcohol withdrawal.” 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.

Finding out what makes salt attractive could reveal a way to help these patients. Previous studies have suggested that dopamine neurons are involved. The Ventral Tegmental Area (VTA) of the brain, where the dopamine neurons sit, is tied up with addiction, wanting and reward, so Eleanor’s project

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- Fellows -

“It’s fun being involved with setting up a new technique and then getting it to work”

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- Introduction - Fellows - -

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

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- Fellows -

DR JENNET WILLIAMS • 2013 Fellow, Cellular Stress Group

slow tumour growth,” explains Jennet. “But the evidence as to whether AMPK is a friend or foe to cancer is conflicting.

It 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 ChainFlorey 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 instead of them upon her. But she enjoys lab work and hopes to continue her current line of research.

Jennet studied medicine in Wales before heading to London’s Hammersmith Hospital. 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 AMPactivated 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 hepatocellular 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 to

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CHAIN-FLOREY Clinical Research Scheme

LECTURERS 2015

Top row, left to right: Dr Julie Glanville, Dr Antonio de Marvao Bottom row, left to right: Dr James Tomlinson, Dr James Ware

DR JULIE GLANVILLE • 2015 Clinical Lecturer As she sits at her desk in a laboratory she hopes will soon be filled with the whirring of refrigerators and incubators, and the whooshing of ventilated workbenches, Dr Julia Glanville prepares for her two-year Chain-Florey Lectureship. “It’s enormously challenging, but I’m still at a very early stage in this exciting opportunity.”

“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 the platform that the CSC provides”

Julie comes to the CSC after completing her PhD training at the University of Oxford, but her path towards becoming a Chain-Florey Lecturer began when she was still an undergraduate student. “I loved tropical medicine and travelling, so I decided to go to Vietnam as an elective student. I wanted to work on research related to infectious

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- Lecturers -

diseases, and then I met a haematologist over there who was doing everything I wanted to do. She was looking at tropical medicine but in a really practical way.”

“The institutes where you really mingle medicine and science are rare in the UK”

After she returned to the UK from her studies abroad, Julie trained as a haematologist in London. “I wanted to do a T cell PhD, so I went to Oxford to do that with Andrew McMichael, looking at HIV. Basically, I got really interested in transplant medicine and how you can use T cells therapeutically to treat viral infections post-transplant, when you are immune-suppressed. But now over the last couple of years this really incredible technology has been developing called chimeric antigen receptor (CAR) engineering, where the T cell changes and recognises other cells and the results are amazing. For example, with some really difficult to treat leukemias CAR engineering can result in an 87 per cent cure rate.”

“The way my brain works when I’m being a doctor is completely different from the way I think about things when I’m being a scientist. It’s the speed of thinking. In medicine you have to make a lot of decisions very quickly. Whereas in science you really need to understand something, and take the time to think about it and work out why it’s not working.

I think the opportunity to look at things differently, and to stop and think about the practice of medicine are some of the luxuries that the Chain-Florey programme provides.”

Julie feels that the field of adoptiveT cell therapy – transferring improved immune cells into a patient – is relatively new, and ripe with opportunities for junior researchers. “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 the platform that the CSC provides.”

Julie believes that the integration of medicine and basic science is important not only to improve the translation of research from the bench to the bedside, but also for training great doctors. “The institutes where you really mingle medicine and science are rare in the UK. In medicine, the training has become very structured and it’s really hard to get the time off to finish your science. That’s the benefit of these MD-PhD Fellowships like Chain-Florey, you can really think about a disease and where it comes from, and break it down to find new, interesting themes to develop in the science. From the medicine you are coming up with genuine problems that people face, and from the science you understand how to pull that problem apart in the lab.”

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- Introduction - 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.

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- Lecturers -

The current standard is just a couple. They recruited some 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.”

academics need excellent time management. “On the clinical side you have to acquire all the skills and knowledge expected from a full time 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.”

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.

“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

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- Introduction - 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.

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.

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

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- Lecturers -

Fibrosis is scarring of the kidney, and usually occurs following an injury or illness, such as diabetes. “It’s not necessarily that 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.

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.

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.

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”

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.

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.”

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- Introduction - Lecturers - -

DR JAMES WARE • 2015 Clinical Lecturer

This year we are delighted to welcome Dr James Ware, who will be sponsored by the Wellcome Trust and joins the CSC as a Chain-Florey Lecturer equivalent. James will join Professor Stuart Cook, who leads the CSC’s Cardiovascular Magnetic Resonance Imaging and Genetics research group. 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 will be exploring computational methods for genome interpretation, with a particular focus on inherited cardiac conditions, and gene discovery in patients with unexplained cardiomyopathies. “We will also be 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.

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CHAIN-FLOREY Clinical Research Scheme

ALUMNI

DR ALLIFIA ABBAS NEWSHOLME • 2011-2015

“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 says she has the confidence of a clinician, able to “talk the language of science.”

Allifia is currently a Renal Registrar at Canterbury Hospital.

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- Introduction - Alumni - -

DR TOMOKI ARICHI • 2009-2012

DR JONATHAN BOND • 2009-2012

Since completing his Fellowship, Dr 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. He also holds a visiting position in the Bioengineering Department at Imperial College, where they are developing new robotic tools for assessing infant motor function.

“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.”

Jonathan works in Elizabeth Macintyre’s lab at l’Hôpital NeckerEnfants Malades Paris supported by a Kay Kendall Leukaemia Fund Intermediate Research Fellowship. Soon he hopes to take up a Clinician Scientist role in London.

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

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- Alumni -

DR ANDREW INNES • 2012-2015

DR ANTONIO DE MARVAO • 2012-2015

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!”

Dr Antonio de Marvao has just been awarded a PhD for his work in the field of cardiac imaging and genetics under the supervision of Professor Stuart Cook and Dr Declan O’Regan at the CSC. Antonio, in collaboration with a large multi-disciplinary team across the CSC and Imperial College London, developed a new approach for highly detailed cardiac phenotyping. He demonstrated that combining 3D cardiovascular magnetic resonance with computational modelling provides high-resolution insights into the earliest stages of heart disease. Having been awarded a Chain-Florey Lectureship, Antonio will now focus his research on the integration of genomic information into his computational models to better understand the factors that influence cardiovascular health and disease.

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

Antonio is a Specialist Registrar in Cardiology in North West London and was recently appointed as a Chain-Florey Clinical Lecturer in Cardiology at Imperial College London.

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- Introduction - Alumni - -

DR THOMAS OATES • 2010-2013

DR AMIT PATEL • 2010-2013

Amit started his Chain-Florey Fellowship in 2010 under Luis Aragon in the Cell Cycle Group. Using 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. Amit completed his PhD in 2013 and returned to clinical training in stem cell transplantation at Imperial College Healthcare NHS Trust in 2014, before moving to the Royal Marsden NHS Foundation Trust in 2015.

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 bioinformatics 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.”

Amit is a Specialist Registrar in Haematology and Intensive Care Medicine based in West London. He also continues translational research on cellular immunotherapy for sepsis and haematological cancer, in his roles as an NIHR Clinical Lecturer at the Institute of Cancer Research and an Honorary Clinical Lecturer at Imperial College London.

Thomas is an NIHR Clinical Lecturer at University College London, and a Specialist Registrar in General Internal Medicine at the North Middlesex University Hospital.

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- Alumni -

DR JAMES TOMLINSON • 2010-2013

DR PHILIP WEBSTER • 2011-2014

“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.

During his PhD, James Tomlinson focused on nitric oxide (NO) signalling in kidney physiology and disease. Using in vitro and transgenic in vivo approaches, James discovered that enzymes acting to increase NO biosynthesis, the dimethylarginine dimethylaminohydrolases (DDAHs), have a significant impact upon both acute inflammatory and chronic fibrotic kidney disease.

James recently began a Clinical Lectureship under the ChainFlorey Scheme and continues to focus on NO signaling. He is also exploring new fields, such as developing a novel technique to better understand gene expression in kidney fibrosis. James will complete his registrar clinical training at the Imperial College Healthcare NHS Trust. He intends to apply for an intermediate fellowship that would fund future research activity while he begins a nephrology consultant role.

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

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- Introduction - Alumni - -

DR JESS ZHAO • 2010-2013

“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.

Jess is currently a trust doctor in the stroke unit at Charing Cross Hospital, Imperial College Healthcare NHS Trust.

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Inside back cover images courtesy of Professor Benjamin Chain and the National Portrait Gallery, London.

Produced by the Grants, Engagement and Communications Facility, MRC Clinical Sciences Centre. Printed by ScanPlus.

CHAIN-FLOREY Clinical Research Scheme

ERNST BORIS CHAIN

ERNST BORIS CHAIN

HOWARD WALTER FLOREY