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Winter 2005/06 News, views and information from the Medical Research Council

In this issue £10m boost for flu research MRC College of Experts The Medical Research Council is set to increase funding of research into influenza Promoting scientific and other emerging infections by £10m. In excellence now and in late November 2005, it put out a call for the future proposals to enhance research to tackle page 2 emerging infections with a pandemic potential. The extra money comes on top Basic thinking of the £1.6m that the MRC had already spent on influenza research in 2005. A look at the importance of This recognition that extra funds for flu fundamental science to research were needed was prompted by a human health mission of MRC experts to Vietnam and page 4 China last October, led by Professor Andrew McMichael, chair of the MRC’s Discussions in progress during an MRC international flu workshop in Infections and Immunity Board.The team

London, December 2005 Andrew StuartPhotograph by MRC wanted to discover more about the spread international of the avian flu virus and to discuss how The mission also visited several institutes in MRC scientists lead collaboration between the UK, China and Vietnam China, where biomedical research capacity is could be improved in the future. It also included growing quickly. Professor McMichael said: mission to China in Sir John Skehel – whose work at the MRC “They’re investing heavily in basic research and October 2005 National Institue for Medical Research has want to translate the findings into new products. page 6 explained how the 1918 flu virus kept its avian flu It was intriguing that there were so few human characteristics but was able to transmit between cases of H5N1 there compared to neighbouring Unit profile humans – Professor Anne Johnson, epidemiologist countries.That could be due to under-reporting, and deputy chair of the Infections and Immunity but equally it could be down to better control of Network visits the MRC Board, and Dr Xiao-Ning Xu, an expert in SARS the infection in poultry by vaccination.” The team Human Immunology at the MRC Human Immunology Unit. has backed efforts to exchange samples and Unit in Oxford information within China and south-east Asia, page 10 Opportunities for collaboration and more widely between World Health Vietnam has the highest recorded number of cases Organization laboratories.They also back short- of human infection by the H5N1 avian virus. The and long-term exchange of scientists. Schools initiatives MRC scientists visited five Vietnamese institutions Helping young people and were encouraged by the fact that officials Preparing for rapid response experience the wanted to co-ordinate the public and animal Looking ahead to the result of the call for excitement of science health responses to H5N1 both nationally and proposals, Professor McMichael said:“Some of the page 16 internationally. They identified three centres for research can begin as early as spring 2006. But we possible collaboration: the Hospital for Tropical also want to fund research which can only start if Diseases in Ho Chi Minh City, the Institute of and when influenza becomes an epidemic or Clinical Medicine and Tropical Diseases in Hanoi pandemic.” Plus and Vietnam’s National Institute of Hygiene and Opportunities, Epidemiology. The party concluded that there MRC Chief Executive Professor Colin Blakemore research roundup, were some urgent research questions, including added:“The strategy we’ve been developing here MRC people and what caused people to become so ill shows that we can move quickly when a health more… and what determined the recovery of about half crisis emerges.” of the patients. >> continues on page 12 2 MRC | network Winter 2005/06

Ensuring scientific excellence through the College of Experts

Network reports on the group of expert scientists who peer review more than 1,500 applications each year for the MRC...

As the UK’s leading public funder of end with reviewing funding applications – membership involved, Colin Blakemore medical research, the MRC must ensure they also have the opportunity to help asked for their views on current issues that the taxpayer’s money is spent on the Council to develop its scientific and in particular, the MRC’s policies on the highest quality science with a real strategy. Members are able to influence supporting clinical research and early- potential to improve human health. and contribute to the MRC’s work career scientists. Clearly welcoming this To achieve this, each research proposal through a range of activities, from annual opportunity for dialogue, they asked received from scientists must be workshops and participation in scientific many interesting and challenging scrutinised by at least three independent showcases to frequent consultations on questions, and offered some very useful experts before the MRC’s Research key issues.All of which means that suggestions.As a result, the members’ Boards decide whether or not to fund it. experience as a College member is an feedback has informed both the MRC’s But with applications now running at excellent grounding for scientists who plans for developing the College and its 1,500 per year across the MRC’s wide are interested in becoming a member of scientific strategy. and diverse portfolio, sourcing the a Research Board or a Training and required number of reviewers presents a Career Development Panel, or one of The workshop participants were considerable challenge. the MRC’s other expert advisory groups. particularly enthusiastic about learning more about their Research Boards’ To meet this need for expert senior scientific portfolios and contributing to scientists who can provide consistently “I look forward to being part development of the Boards’ scientific high-quality reviews and who understand of a thriving College of Experts, strategies. So the next step for the MRC the MRC’s work and strategic objectives, rather than simply one of many will be five workshops in 2006, each the Council set up a College of Experts involving College members, their in 2005.The College is made up of more reviewers working separately and individual MRC Research Board and the than 1,000 scientists who meet these without being able to see or input Board’s Strategy and Portfolio Overview demanding requirements, and who have into the bigger picture.” Group.The aim is for College members agreed to review at least six research Member of College of Experts to be able to hear more about their proposals per year. Each member is Board’s work, and to gain an insight into affiliated to one of the MRC’s five the work of the MRC’s Strategy Research Boards, so that the College’s A key relationship Overview Groups for clinical, public collective expertise spans the entire It goes without saying that building up a health and basic research.Another key range of the Council’s scientific portfolio. strong relationship with the new College theme of the day – to which members of Experts and facilitating communication will be encouraged to contribute – will Colin Blakemore, Chief Executive of the with and between its members is a key be the MRC’s priorities for funding from MRC, says:“The MRC’s reputation is built priority for the MRC. One way that the the Science Budget in the Government’s on the quality of science that it supports. MRC has been stimulating such dialogue 2007 Comprehensive Spending Review. We are very grateful to the members of and synergy was through a series of To complement these strategically the College of Experts for their central introductory workshops for new focussed workshops, individual members role in peer review, which underpins the members in summer 2005. Held in will be offered the opportunity to decisions we make.The College also Edinburgh, Birmingham, Bristol and observe their Research Board in action provides an essential link between the London and attended by more than 300 at a funding meeting. Boards of the MRC and the research members, the workshops gave them the community they serve.We look to the opportunity to meet Chief Executive Impact of Freedom of Information College to help us to develop our strategic Colin Blakemore, other MRC staff, and Act plans in ways that reflect the strengths one another.The format was a mixture Another topic of interest at the and needs of UK medical research.” of briefings, question-and-answer introductory workshops was the Freedom sessions and informal group discussions. of Information Act, which came into force Involvement in the bigger picture on 1 January 2005.The Act gives What makes the College unusual is that After the participants had learnt more individuals a legal right to obtain the members’ role does not begin and about the MRC and what their information held by public authorities and Winter 2005/06 MRC | network 3

universities, which raises serious questions about the anonymity and confidentiality of peer review reports. College members will be reassured to learn that the MRC and the other UK research councils have now agreed a common Freedom of Information peer review policy. It details what information the research councils will release, when, and to whom, Informal group discussion during an introductory College of Experts workshop in London, July 2005 throughout each stage of the peer review process.As Jerry Folkson, MRC Business CD. It will also be providing more web- – and encourage internationally Development Manager, confirmed,“The based guidance about reviewing, including competitive, appropriately costed MRC, along with the other research use of the MRC’s online reviewing system. applications, with a balance between councils, is improving the transparency of short-term and long-term programmes. its peer review process. However, we will Easing the load continue to preserve reviewers’ In 2004 the MRC made major changes to To help College members schedule their anonymity, and will not release any its funding schemes to give researchers reviewing commitments into their overall identifying details about reviewers in fewer, simpler and more flexible options. workload, the Research Management response to information requests under This has led to a dramatic increase in the Group will be highlighting peer review the Act.” number of applications, which has ‘hot-spots’ on the MRC website increased the pressure on both the MRC alongside deadlines for receiving Full economic costing and its reviewers.To help manage the applications. Many College members have asked problem, the MRC has reduced the whether the introduction of full number of reviewers per application to economic costing of applications is likely between three and five, and publishes a Interested in joining the College? to lead to any changes in what is wider range of award statistics to help Are you are a biomedical scientist at required when reviewing an application. applicants assess the likelihood of success reader or equivalent level, who is willing The answer is no – the reviewer’s role before submitting an application. to review at least six research proposals remains first and foremost to comment Applicants can now view online overall a year and to spare the time to become on the scientific quality and importance funds available, numbers of applications involved in helping to develop the MRC’s of a proposal, and then to assess its already submitted, average size of grant, scientific strategy? If so, the MRC would ‘value for money’ on the basis of award rates by MRC Research Board and be pleased to hear from you. Please whether the level of resources are university, etc. The aim is to discourage contact Anne-Marie Philp of the MRC justified – or in some cases, sufficient – low-quality or speculative applications – Research Management Group at to carry out the research effectively. which waste valuable reviewing resources [email protected].

Training Find out more online All new members have received a basic CD-format induction into the MRC and College of Experts membership their crucial role in the Council’s work. www.mrc.ac.uk/about-college_of_experts_membership.htm Feedback from the 2005 workshops 2005 workshops: report, programme and presentations revealed that many members would find www.mrc.ac.uk/index/about/about-organisational_structure/about-college_ of_ it helpful to receive further training and experts/about-college_of_experts_annual_meetings.htm mentoring, and peer review guidelines. MRC’s Freedom of Information peer review policy The MRC will therefore be holding http://www.mrc.ac.uk/about-foi_peer_review training sessions during its 2006 College Data on MRC grant awards workshops and is looking at ways of http://www.mrc.ac.uk/index/funding.htm developing the content of the induction 4 MRC | network Winter 2005/06

Basic thinking

Although 2005 brought increased support for clinical research, basic research remains the bedrock of biomedical science, underpinning the treatments and diagnostics of the future...

As Network readers will have noticed, Meanwhile, at the LMB, Dr Matthew late 1980s, Professor Sir Gregory Winter over the last year the MRC has been a Freeman’s research into the mechanisms began applying protein engineering leading voice in discussions about taking of growth-factor receptor signalling has technologies to the long-standing problem forward translational and clinical research led to the discovery of a family of of creating ‘humanised’ monoclonal in the UK, building on the knowledge intramembrane proteases, called antibodies. His success created a revolution gained in the past 50 years of fundamental rhomboids, which are turning out to have in the pharmaceutical industry, spawning a research.With all this enthusiasm for many and varied functions in both animal new and continually expanding range of translation, it is important to remember cells and bacteria. Most excitingly, Dr antibody-based treatments. Sir Gregory’s that the clinical applications of the future Freeman’s work has suggested that discoveries have been used to create will depend on the fundamental research rhomboids play a part in a number of therapies for cancer, asthma, psoriasis, of today and tomorrow.The MRC, with medical conditions, including parasitic multiple sclerosis and arthritis, and for hundreds of its scientists engaged in infections, such as malaria, and bacterial prevention of kidney transplant rejection. world-class basic research, remains as pathogenicity. committed as ever to ‘blue skies’ Professor Mark Pepys has been studying investigations.And the Council envisages Discoveries like these are, of course, amyloidosis since the late 1970s, moving that the new efforts in clinical research – exciting in their own right. But, as with all from basic understanding to treatment. from experimental medicine to the UK the best of the MRC’s innovative basic This serious condition occurs when Biobank – will provide valuable research, they do more than simply push normally soluble proteins are deposited as information to guide the next steps in back the frontiers of intellectual abnormal insoluble fibres around and fundamental research. Basic and applied endeavour. Basic research feeds a pool of between cells, damaging the structure and research rely on each other for success – ever-increasing knowledge about cells and function of the affected organs. both are vital steps in the journey physiological systems, which in turn Amyloidosis is responsible for one per towards improved health and economic generates opportunities for translational thousand of all deaths in the UK. prosperity in the UK.This is why the work and eventual clinical application. Professor Pepys’ MRC-supported work of scientists such as Dr Matthew research, into both the basic mechanisms Freeman of the MRC Laboratory of A history of translational benefits of the condition and its clinical diagnosis Molecular Biology (LMB) in Cambridge The MRC’s history is rich with examples and treatment, led to the establishment of and Dr Steve Gamblin of the MRC of basic research that has subsequently the UK NHS National Amyloidosis Centre National Institute of Medical Research been exploited to yield improvements in at the Royal Free Hospital and University (NIMR) in north London is as important human health. One notable example from College London in 1999.The centre to the MRC’s future plans as that of the LMB started with the development of investigates the largest, most diverse clinical and public health researchers. monoclonal antibodies by César Milstein cohort of amyloidosis patients in the and Georges Köhler in the 1970s. In the world and advises about their treatment, At the NIMR, Dr Gamblin has been investigating the structures of proteins involved in cellular signalling and in infectious and metabolic diseases. His recent collaboration with Sir John Skehel’s influenza laboratory has revealed the structures of influenza haemagglutinins, which bind to receptors on the surface of animal cells and usher in the first stages of virus infection. Steve and his team have also identified the structure of haemagglutinin from the 1918 pandemic virus, providing vital clues as to why this virus spread so efficiently, with important messages about the new pandemic that we may be facing. Structure of influenza haemagglutinin Winter 2005/06 MRC | network 5

under the clinical directorship of “We recognise the vital need to safeguard the interests of fundamental Professor Philip Hawkins, and has greatly bioscience and we are continuing actively to develop our basic research improved their diagnosis, management and portfolio. Maintaining world-class research that extends from the most survival. Professors Pepys and Hawkins have developed a new drug, CPHPC, that basic to the most applied puts the MRC in a strong position to fulfil its specifically targets serum amyloid P mission to improve the health and wealth of the nation.” component, a protein universally present Professor Colin Blakemore, Chief Executive of the MRC in amyloid deposits. CPHPC is being developed for large-scale clinical testing preventive measures for these devastating To maintain the existing community and and may find application in Alzheimer’s conditions. nurture the next generation of skilled disease as well as systemic amyloidosis. researchers, the MRC provides career Strategic perspectives development training schemes, along with Long-term approaches No-one can foresee where the next increasing investment in state-of-the-art Recognising that it can sometimes take major discoveries and technical facilities and equipment. many years for the translational benefits developments in basic research will come of basic research to become apparent, the from, or their possible impacts in diverse The Basic Research Overview Group: MRC believes that long-term funding of and apparently unrelated fields. So, in The MRC is actively developing its basic basic research is essential. For example, addition to its long-term strategic vision research portfolio and in October 2005 the MRC’s support for research into set up a new advisory body – the Basic synaptic plasticity reaches back to the Research Overview Group – to help achieve 1970s, when Professor Tim Bliss of the this aim.The group is responsible for cross- MRC National Institute for Medical research board oversight of the MRC’s Research, together with Terje Lømo of the basic portfolio, and sits alongside two University of Oslo, published the first other overview groups – for clinical research detailed account of long-term and public health research. It is chaired by potentiation (LTP) – the rapid and Professor Kay Davies, MRC Council sustained increase in the efficiency of member and Honorary Director of the synapses in a brain structure called the MRC Functional Genetics Unit in Oxford. hippocampus. In 1986, the link between such synaptic ‘plasticity’ and behaviour The Basic Research Overview Group will was established by another MRC- monitor trends in research and funding supported scientist, Professor Richard patterns and advise the Council about Morris of the University of Edinburgh, the balance of scientific areas within the who discovered that interference with basic portfolio.To ensure a coherent LTP disturbs spatial learning in rodents. approach, it will foster links with the The field received a further boost in 1999 clinical research and public health when the MRC Centre for Synaptic research overview groups and its Plasticity was established at the University discussions will incorporate views that of Bristol, with Professor Graham emerge from the individual research Collingridge as Director. Graham has Microscopic images of amyloid deposits in the kidney board strategy groups.The group is also made a major contribution to our responsible for identifying opportunities understanding of the complex molecular for the funding of basic research, the MRC for increasing the effectiveness of the mechanisms that underlie LTP and other must also be able to recognise opportunities MRC’s links with the biotech and forms of synaptic plasticity. Dysfunction and to take risks in curiosity-driven pharmaceutical industries, with overseas of synaptic plasticity is now believed to science, for these can hold the key to research partners and with other UK be involved in various psychiatric and significant improvements in treatments. funders of basic biomedical research. neurological disorders, including The MRC focuses on funding a broad Alzheimer’s disease, epilepsy and portfolio of innovative and high-quality To support the work of the Basic ischaemic brain injury. The efforts of research that underpins key translational Research Overview Group, the MRC Professors Bliss, Morris, Collingridge areas and takes advantage of expertise in regularly looks at the range of expertise and colleagues could prove key to the both the biological and physical sciences. on its Research Boards to ensure a development of new treatments and Developing research talent is also vital. balance between basic and more applied disciplines. For example, the Physiological “Biomedical science is evolving very rapidly.The work of the Basic Research Systems and Clinical Sciences Board is Overview Group will ensure that the MRC continually reviews its basic currently recruiting an additional member research portfolio, and so remains at the international forefront of with expertise in basic cell biology and its application to physiological systems and bioscience and a leading player in innovations in healthcare.” the maintenance of health. For further Professor Kay Davies, Chair of the MRC Basic Research Overview Group details, see “Opportunities” on page 7. 6 MRC | network Winter 2005/06 mrc international mrc international mrc international

MRC visit shows time is right for collaboration with China

Chief Executive Colin Blakemore recently led an MRC delegation to China to explore opportunities for research partnerships. Network finds out more…

As mentioned in our front page story, in and its increasing investment in science.” being redrawn and nowhere faster than in October 2005 a team of scientific experts On visits to Beijing, Shanghai, Guangzhou China.” from the MRC visited China to meet with and Shantou, MRC delegates were struck their Chinese counterparts.The aim of by the intensive investment being targeted Professor Ron Laskey and Professor the two-week mission was to raise the at new buildings and state-of-the art Ashok Venkitaraman of the MRC Cancer MRC’s profile in China and to assess the equipment – currently running at around Cell Unit, and Professor Qimin Zhan of potential for scientific collaboration in 1.4 per cent of China’s GDP.It is clear the National Laboratory of Oncology, research into cancer, neuroscience, that China’s strategy is to attract back Beijing, hosted a British Council Café infectious diseases and biotechnology. expatriates to help develop a knowledge- Sceintifique event.The evening involved based economy. three talks and more than two hours of questions from the audience of around After a second Memorandum of 120 students, academics and members of Understanding had been signed – this time the general public.As Professor Laskey with the Chinese Academy of Sciences later pointed out, the enthusiastic (CAS) in Beijing – an MRC delegation participation of this last group was visited several CAS institutes in Shanghai. evidence of growing public interest in Professor Brian Anderton, who led the science in China. group, said about the Academy’s neuroscience activities: “There is considerable complementarity of science between the UK and China… establishing Professor Chen Zhu,Vice-President of the Chinese stronger links has the potential to enhance Academy of Sciences, and Professor Colin Blakemore with the Memorandum of Understanding the international position of both countries.”

The mission was part of the UK-China Public engagement was another important Partners in Science 2005 initiative, a year- strand of the MRC visit. Freelance artist long event supported by the Chinese and Judith Devons held workshops in two UK Governments. Led by MRC Chief Beijing high schools, inspired by research Executive Colin Blakemore, the 20 at the MRC Toxicology Unit in Leicester. delegates included directors of UK More than 50 pupils and teachers research centres, research programme explored the interface between science Artist Judith Devons and a pupil of Ba Yi High School, leaders, clinicians and MRC head office and art through screen-printing – with Beijing, during one of the screen-printing workshops staff.The fortnight’s activities ranged from Colin Blakemore joining in with gusto to scientific workshops on cancer and produce his own souvenir print.The As the MRC mission prepared to return neuroscience and fact-finding site visits, to pupils’ group artwork, a brightly coloured to the UK after two fascinating weeks, public engagement events with schools wallhanging displaying their individual Colin Blakemore summed up the group’s and the public. screen-prints, was exhibited in the British experience in China: “We have seen some Ambassador’s residence during a impressive developments in science during The group’s visit began with the signing of reception in honour of the MRC mission. our visit, and there are great opportunities a Memorandum of Understanding with Commenting on the MRC’s visit and the for collaboration with UK scientists. the National Natural Science Foundation signing of the Memoranda of During 2006, the MRC will be developing of China (NNSFC), during which Colin Understanding, the Ambassador, Sir a series of initiatives with key agencies Blakemore told the MRC’s hosts that Charles Hum, said: “We think these such as NNSFC and CAS to foster new “The UK is watching with admiration the developments are very exciting and very science programmes between our two impressive growth in China’s economy timely…The map of world science is countries.” Winter 2005/06 MRC | network 7

Opportunities

Research Board applications – MRC Research Board October/November 2006 vacancy

All applications must be costed on a full economic basis. The Physiological Systems and Clinical Sciences Board has a Molecular and Cellular Medicine vacancy for a senior scientist with Full application Peer Review Board meeting* expertise in basic cell biology and 4.5.06 May–July 2006 12–13.10.06 its application to physiological systems and maintenance of health, Infections and immunity and research interests in one or Full application Peer Review Board meeting* more of the following areas: 11.5.06 June–August 2006 19–20.10.06  The regulation of cellular Physiological Systems and Clinical Sciences function Full application Peer Review Board meeting*  Cell signalling and signalling 18.5.06 June–August 2006 24–25.10.06 pathways

Neurosciences and Mental Health  Ion channel regulation

Full application Peer Review Board meeting*  Cellular and molecular imaging. 25.5.06 June–August 2006 6–7.11.06 For further details see Health Services and Public Health Research http://www.mrc.ac.uk/about- Full application Peer Review Board meeting* board_recruitment 1.6.06 June–August 2006 8–9.11.06 Closing date for applications: * Normal decision point 9 February 2006.

Calls for proposals Good news for those

Influenza research seeking funding Intentions to apply: n/a Deadline for full applications: 20.2.06 Traditionally, if a scientist works in a research institute that receives Methodology and implementation support from a funding The aim of this call is to pump-prime and strengthen the Health Services and organisation, they are prevented Public Health Research Board portfolio of methodological research. from applying to another funder The budget for the call is £4m and the Board anticipates that between 10 and 20 for response-mode funding. proposals will be funded. Intentions to apply: 27.1.06 Deadline for full applications: 1.3.06 The good news is that this barrier to funding is beginning to disappear For further information visit www.mrc.ac.uk/funding – the MRC, the Biotechnology and Biological Sciences Research Council and the Wellcome Trust Milstein Fund have finalised agreements with one The Milstein Fund aims to provide support for innovative research with potential another to extend eligibility for for high payback.A budget of £3m has been allocated and it is hoped that up to response-mode support to 10 awards will be made.The initiative is being piloted in 2006/07, although the researchers based in institutes MRC intends to continue to make funds available for this type of research in supported by these funders. subsequent years. We hope that other organisations Full details of the call and eligibility to apply will be announced on the MRC will soon be following our lead in website in early March with an application deadline of 21 April 2006. removing obstacles to funding. 8 MRC | network Winter 2005/06

Body fat – there’s more to it than meets the eye Few of us would question the health risks of obesity. But there is another side to the body fat issue, as researchers at the MRC Clinical Sciences Centre are showing…

Nowadays, virtually all of us are aware of application of MRI scanning.The new resistance and type 2 diabetes, compared the relationship between obesity and ill technique enables them to create whole- to subjects who have similar levels of health.An increased risk of insulin body-fat maps of volunteers and patients body fat but have deposited most of it resistance, heart disease, type 2 diabetes, in a matter of minutes, including for externally. And, as Dr Jimmy Bell told stroke, high blood pressure and neonates and premature infants. It is giving Network, "Through a series of osteoarthritis are just some of the proven the researchers a unique insight into the interventional studies we are beginning to hazards of obesity. But scientists still don’t environmental and genetic factors that find that different life-style modifications fully understand the mechanisms contribute to how a person’s body can impact differently on different fat underlying this association, which is deposits and mobilises fat. depots and hence on health and disease. limiting their ability to develop new, more effective treatments. Nor have they fully indentified the equally important benefits of body fat.To help throw light on these issues, the MRC Clinical Sciences Centre (CSC) and Imperial College London have brought together researchers from a range of disciplines – basic scientists Dr Jimmy Bell and Dr Louise Thomas, clinical researchers Professor Gary Frost and Professor Neena Modi, and physicist Professor Jo Hajnal. Using MRI and PET imaging techniques, molecular genomic investigation and clinical research, the team aims to uncover the role of adipose tissue in health and disease.

Moving beyond the body mass index During the last 10 years or so, there has been a growing awareness that there is more to body fat than meets the eye. In other words, the health risks of body fat can be as much to do with where it is distributed in a person's body as with the Thin on the outside, fat on the This is leading to new treatment amount of fat that they show externally. inside strategies that focus on achieving the The body deposits fat in at least eight As a result of their investigations, the optimum benefits for health – such as different places, within adipose tissue team has found themselves faced with a combining changes in diet and in physical depots or ectopic fat depots.Adipose surprising new body type, one which activity – rather than concentrating on tissue depots include external reveals the limitations of the traditional maximum weight loss.” subcutaneous fat, fat within the abdominal body mass index (BMI) as a tool for cavity, popliteal fat and that between understanding the relationship between The good, the bad and the ‘ugly’ muscle fibres, while ectopic depots are fat body fat and disease.They have identified The team now believes that adipose within muscle, liver, pancreatic and heart the ‘thin on the outside, fat on the inside’ tissue is much more than a simple cells. Each of these depots appears to individual, who has a normal BMI and low storage organ for excess energy.They contribute differently to the body’s external body fat content, but see it is a highly refined, physiologically homeostasis.To find out more about disproportionately high levels of intra- tuned organ that has significant effects them, including their role in the abdominal fat and ectopic fat deposition. on many of the body’s functions, development of insulin sensitivity and type These people have been shown to have including total energy homeostasis, 2 diabetes, the team has pioneered a new an increased risk of developing insulin appetite, satiety, fertility, immune Winter 2005/06 MRC | network 9

response, growth and a sense of well- Researchers and public join being. For example, popliteal depots include fat cells surrounding the forces over autism lymph glands shown to be essential in the process of immune response in In September 2005 the MRC and the for interventions.We are here, as parents, inflammation and disease.And if National Autistic Society hosted their to learn more about autism and influence adipose tissue malfunctions or is second Autism Forum in London. More the scientists.They need to marry parents’ absent – as happens in some than 120 parents and others with an priorities with science and take it forward environmental or genetic conditions interest in autism from there.” – this can lead to severe health spectrum disorder complications by causing excess (ASD) came to meet Research highlights internal (ectopic) fat to be deposited. MRC-funded autism The research “Through the use of MRI techniques researchers and highlighted included we have recently reported that nearly discuss where their several of the newly- 40 per cent of the UK population needs fitted into the funded studies.The shows mild to severe fat deposits in research agenda. Pre-school Autism the liver,” said Dr Bell,“while human Communications Trial, subjects with newly identified genetic Background to led by Dr Jonathan mutations, with little or no external the event Green of Manchester adipose tissue, show significant deposits Dialogue between University, is the David Braunsberg, an artist with Asperger’s in the liver, pancreas and muscle.” MRC-funded largest randomised syndrome, displaying some of his etchings scientists and the and hand-painted scarves at the Forum. controlled trial of a This scientific appreciation of the value public began in 2001, non-drug treatment for of adipose tissue contrasts strikingly when the MRC’s Review into the Causes autism yet undertaken. Professor Declan with the western world’s current and Epidemiology of Autism sought Murphy of the Institute of Psychiatry in aversion to body fat.While scientists expertise and opinion from outside the London outlined approaches to brain such as the team at CSC marvel at the scientific community.The Department of imaging to identify differences in neural hidden ‘beauty’ of adipose tissue, the Health and the Scottish Executive networks between individuals with autism increase in obesity in the general provided £2.75m to take forward the and those with Asperger’s syndrome. population and our constant review’s recommendations. The MRC Professor Jean Golding of Bristol bombardment with unrealistically slim then set up an Autism Steering Group, University described how data from the role-models by the media has made chaired by Professor Carol Dezateux of “Children of the Nineties” study, which external body fat public enemy London’s Institute of Child Health, to looked at how environment, experiences number one for both sexes. encourage the spread of research and genes influence children’s health, networks and multidisciplinary approaches behaviour and development, is being used Restoring a sense of balance in order to stimulate new thinking in to explore environmental-genetic The flip-side of this increasing obsession autism research. By summer 2005 the interaction in children with ASD. Dr with obesity is the ‘ideal’ of low/zero MRC had funded six high-quality research Francesca Happe of the MRC Social and body-fat, a paradoxical state of affairs proposals, covering: environmental risk Genetic Developmental Psychiatry Centre through which our society is in danger factors, cognition and behaviour, brain at the Institute of Psychiatry, discussed her of losing a sense of the self and the imaging, language and communication, research exploring how the autistic mind human body as a fully functioning whole. memory and Asperger’s syndrome, and a functions.The overall context for these clinical trial investigating the effects of studies was provided by Dr Tony Charman One all too graphic illustration of this enhanced parental communication on pre- of the Institute of Child Health, who is the fact that liposuction, one of the school children with autism.These grants reviewed the UK scene for autism most extreme (and increasingly totalled £3.1m, almost doubling the MRC’s research, and by Dr Rob Buckle of the popular) forms of body fat reduction, investment in ASD research. MRC and Angie Lee Foster of the National is now so common that in some Autistic Society, who discussed the national countries the waste fat from these Forum activities policy context for research priorities and operations is becoming an During the day MRC-funded researchers reported on current efforts to enhance environmental hazard! So it is introduced their early-stage work.The collaboration between funding agencies. heartening to know that, through the audience ranged from patient group The breadth and depth of the research use of cutting-edge imaging and representatives to parents of recently presented illustrated the challenges faced molecular methodology, scientists at diagnosed children, with differing levels of by autism researchers. Nevertheless, most the Clinical Sciences Centre are knowledge about ASD.They were eager to participants thought that progress was helping to redress this worrying make contact with others in similar being made, and that the MRC is making a imbalance, by revealing the importance situations and to quiz the researchers. As significant contribution to autism research of body-fat and its true relationship to one parent said,“Ever since my child was and is helping to promote communication our health and well-being. diagnosed with ASD we have been looking between families and researchers. 10 MRC | network Winter 2005/06

Centre profile: MRC Human Immunolog

The increasing globalisation of infectious disease is a major challenge to human health. T Immunology Unit is a key player in international efforts to combat this threat, and in rese diseases involving the immune system...

The immune system is crucial to human involving three senior MRC clinical cells, so that the immune system does not health. Our ability to identify and destroy fellows, a Wellcome Trust senior fellow, recognise them as being infected and the invading pathogens involves complex and a scientist recruited from Denmark, virus survives and replicates. networks of interacting cells and Lars Fugger. molecules. Understanding precisely how The HIU has been involved in the the system works at the cellular, genetic “The unit’s initial interest was on how the development of a number of candidate and molecular levels will help in the immune response deals with viruses, with vaccines for HIV that are currently in development of new therapies for diseases a big but not exclusive focus on HIV,” says various stages of clinical trials. It is also such as AIDS, avian flu, multiple sclerosis, Professor McMichael.“We subsequently part of a large international arthritis and eczema.This is the business broadened it to cancer programme that was recently of the MRC Human Immunology Unit immunology and studies launched with funding from the (HIU) based at the John Radcliffe Hospital on autoimmunity, with USA National Institutes of in Oxford. a strong core of basic Health to look at how immunity work.” the immune system It is no coincidence that the unit sits only responds during the a few yards from the bustling entrance of The HIU now has very early stages of one of the world’s most famous teaching eleven research infection. In some hospitals: the work of the unit lies squarely groups and people the virus gains at the intersection of fundamental employs about a foothold early on molecular science and clinical research. 100 staff in total and is present at relatively and has an annual high levels, whereas in Creating the big picture budget of between £3.5m others the initial levels are The HIU, located in the Weatherall and £4m, which includes much lower.“We think the Institute of Molecular Medicine, was funding from both the MRC immune response is playing an founded in 1998 under the directorship and external sources.While each of important role in setting these initial of Professor Andrew McMichael as a the groups carries out its own research, merger of two MRC programme grants, often into diverse aspects of the human immune system, all the research is “It could be that the (HIV) virus is contributing to a single ‘big picture’ of sitting harmlessly in the body’s cells, The human immune system human immunology, and much of the but that the immune system over- work is complementary. reacts in some way.” The human immune system consists of a remarkably elaborate series of defence HIV, influenza and the immune Professor Andrew McMichael, Director, mechanisms against potentially harmful Human Immunology Unit agents that continuously threaten the response body's health.The body takes a multi- Four HIU research groups – led by faceted approach to defending itself, from Professor McMichael,Tao Dong,Tomas levels, which can have a significant presenting straightforward physical Hanke and Xiao-Ning Xu – study the influence on the subsequent progression barriers to using highly complex adaptive human immune response to HIV. of disease,” Professor McMichael says.“If systems by which specialised cells we can identify the features of a good recognise the presence of pathogens and mobilise other cells to destroy them. “A lot of the work is trying to understand immune response as against a poor one, A key element of the human immune why patients who are infected with HIV we can use this knowledge to help us response involves Tcells.There are can progress to disease very differently,” design more effective vaccines.” different types of Tcell involved in says Professor McMichael.“In some recognising and destroying infected cells. people disease progresses very rapidly, The extensive work on HIV has yielded Tcells become activated when receptor while others can survive for 15 to 20 important insights into viral infections proteins on their surface are presented years.” One promising line of research has generally, including avian flu and the virus with antigens – small protein fragments of invading pathogens – by other specialised been into a protein produced by the virus that causes SARS (severe acute cells of the immune system. called Nef, which subtly alters the surface respiratory syndrome). One important of infected cells.This ‘camouflages’ the question with these diseases is whether it Winter 2005/06 MRC | network 11 ogy Unit

. The MRC Human research into other

is the virus itself that is causing people to die, or whether it is the immune response that is the problem. As Professor McMichael observes,“It could be that the virus is sitting harmlessly in the body’s

cells, but that the immune system over- Photograph courtesyArchitects of BG5 reacts in some way.” The Weatherall Institute of Molecular Medicine, where the HIU is based

Researchers in the unit have recently effectively barges the phosphatase out of Cutaneous immunology started a collaboration with colleagues in the way.“We believe that this exclusion of Dr Graham Ogg is interested in the Vietnam, where techniques developed in the phosphatase upsets the balance of immunology of the skin and his group has the HIV work will be applied to the avian phosphorylation and dephosphorylation, made a potentially significant flu virus (see page 1). which acts as the trigger for the breakthrough in the understanding of activation, kicking off the proliferation of what causes eczema.“We believe that the Professor John Bell’s group, meanwhile, is Tcells,” Professor Davis says.“What this root cause could be because some people making significant advances in understanding suggests is that we might be able to use have increased populations of a common the immune response to the influenza other ways to cause the segregation of bacterium, Staphylococcus aureus, on their virus.When a virus invades the body, the phosphatase from the receptor – with skin,” Dr Ogg says. Most of us have this fragments of its protein coat are antibodies, for example – and thereby organism present on our skin, but people presented as antigens to the immune manipulate the signalling process to either with eczema appear to be partially system. In influenza there appears to be a increase or decrease Tcell proliferation.” deficient in the natural antimicrobial common response by Tcells in most defences, which allows the bacterium to individuals, suggesting that certain antigens Immunological origin of arthritis proliferate.The presence of so many of are crucial, or “immunodominant”. Dr Paul Bowness’s team is studying the these bacteria stimulates skin cells called Antigens are the central component of immunological origin of certain forms of keratinocytes to produce so-called HLA vaccines, and the development of effective arthritis, and in particular ankylosing class II molecules on their surface, which vaccines relies on the identification and spondylitis, which usually occurs in young are otherwise not present.The HLA isolation of key antigens. men and results in swollen joints and a molecules in turn grab on to fragments of painful back. More than 95 per cent of proteins from house dust mites, dog and sufferers have an unusual type of HLA cat fur, and pollen, and present them to Tcell biology group molecule on the surface of their cells. HLA the immune system as harmful foreign The group led by Professor Simon Davis is a protein that occurs on cells in the invaders.“Tcells then release substances and Dr Ed Evans is investigating the body, enabling them to communicate with to react to what are apparently infected mechanisms by which Tcells are initially the immune system.The team is trying to cells, causing inflammation,” says Dr Ogg. activated – a central event in the immune understand why the presence of this “If our ideas are correct, this has clear response.When the antigen – a protein particular variant of HLA, called HLA B27, implications for the treatment of patients, fragment from a virus, for example – is hugely increases the chances of getting by reducing the bacterium population on presented to a Tcell receptor, a the disease.“These molecules are the skin and the amount of allergens such biochemical trigger is pulled. Professor important in helping the body fight off as dust mites.” The team hopes to begin a Davis and his colleagues believe that the viruses, and this particular one is especially clinical trial shortly. status of the receptor is determined by a good,” Dr Bowness says.“We think that delicate balance between two antagonistic the abnormal form of the molecule Immune-cell trafficking chemical processes occurring at the stimulates the immune system in an A key aspect of the human immune receptor protein called phosphorylation abnormal way, resulting in the production system is the constant movement of and dephosphorylation.These processes of molecules that cause damage and immune cells between the blood and are carried out by enzymes called inflammation. If we can identify the form tissues, and between tissues and the phosphatases and kinases, which normally of the molecule that is causing the lymphatic system, a network of vessels have equal access to the receptor.When problem and then block it, we might be running throughout the body that carries the antigen is presented, however, it able to ‘switch off’ the arthritis.” >> page 12 12 MRC | network Winter 2005/06

<< infection-fighting cells.“These events are discoveries that have allowed lymphatic system sometimes fails to differentiate pivotal to the inflammatory process and vessels to be extracted from tissues and between an invading pathogen and the are fundamental to generating an immune reconstituted in the laboratory. body's own cells in autoimmune diseases response,” says Professor David Jackson, such as multiple sclerosis (MS). By the who leads the group that studies this type Tumour immunology very nature of their job,Tcells must be of cellular trafficking. Understanding the Professor Enzo Cerundolo's laboratory highly adaptable in order to recognise processes involved at the molecular level studies how the immune system many different antigens, but this also could lead to new ways of controlling recognises cancer cells, with the ultimate makes the system inherently prone to inflammation, for example, or help in the aim of developing vaccines against cancer. mistakes. It appears that multiple sclerosis generation of vaccines. The idea behind a cancer vaccine is to occurs when a variety of genetic and environmental factors combine in a “If we can understand particular way.“The only identified how the immune genetic risk factor associated with MS response controls relates to certain HLA genes,” says Professor Fugger.“We are trying to viruses we are in identify the function of the individual a much stronger genes. Overall there appears to be an position to design interplay between a certain Tcell effective vaccines.” repertoire, environmental factors such as viruses, HLA genes and other, Professor Andrew McMichael (left), Director, unidentified genes.” Human Immunology Unit The work of the HIU demonstrates just how complex the human immune system is, involving precise interactions between present the immune system cells, molecules and genes. Slowly but with antigens specific to surely its researchers are beginning to different types of tumour piece together this immensely detailed so that the body can arm jigsaw, constantly improving our ability to itself in advance and treat debilitating diseases and combat life- recognise and destroy threatening infections. rogue cells before they become established. Continued from page 1 “There are three main issues,” says Professor Professor Blakemore went on to Cerundolo.“We need to say,“The Vietnamese and Chinese Migration of immune cells across the learn how to immunise, we need to be authorities are well aware of the lining of blood vessels and into tissue able to monitor the immune response, threat and are keen for their best involves a protein receptor on the surface and we need to identify the antigens.” The scientists to work with ours.” of the cells called CD44, which binds to a team has achieved the latter two, and the He also played down the suggestion large carbohydrate molecule called big challenge is to learn how to package that the MRC had reacted to panic hyaluronan, or HA. In pioneering work, the antigen in such a way that it can get and hype in the media over H5N1: Professor Jackson’s group, together with into the body and stimulate the immune “We’ve been planning this strategy Professor Martin Noble at the Laboratory system correctly. for months – it was an unexpected for Molecular Biophysics, University of coincidence that our work became Oxford, has crystallised CD44 and The team is adopting a ‘prime-boost’ news just as bird flu reached Europe.” determined its three-dimensional approach, where synthetic antigen structure.The group has also bound proteins are first presented to the body in The MRC’s mission to China helped together CD44 and HA, crystallised the a special mixture of chemicals to ensure a to shape an international workshop resulting structure and elucidated its 3-D powerful initial response, followed by a held in London in December 2005. characteristics.“In this way we have ‘boost’ in which the antigen is wrapped At the event, experts looked at how shown exactly where the interaction within a harmless virus. The team has the virus is transmitted from birds between the two molecules occurs and worked extensively on melanoma and is to people, its virulence and strategies we understand what kind of interaction is now looking at colon and prostate cancer. for effective vaccines and antivirals. involved,” Professor Jackson says.“This Their discussions helped to allows us to design small molecules that Mechanisms of autoimmunity determine a subsequent call for could interfere with the process.” The Professor Lars Fugger’s team is trying to research proposals by the MRC. group has also made important understand why the body’s immune Winter 2005/06 MRC | network 13

Translational research set to benefit from shared DNA resource As the UK DNA Banking Network sends its first samples for testing, Network takes a look at this pioneering service...

In 2000 – three years before the final back-up in a nearby UK Biobank facility. human genome sequence was completed – the MRC recognised that once this Both centres have ISO9001 certification, groundbreaking knowledge was published, which gives assurance that procedures for genetic epidemiology would be needed to consistent quality and continuous quality translate it into human health benefits. improvement are followed. Their state-of- Very soon afterwards the MRC the-art facilities include automated tube, announced its plan to meet this need by plate and liquid handling to eliminate Home page of the new UK DNA Network website creating a national DNA banking network. error arising from manual processing and retrieval, which can run as high as 10 per Researcher-collector collaboration Six years – and a lot of effort – later, the cent in conventional labs. And because The resource clearly reduces the costs UK DNA Banking Network has just the samples are all managed in the same of research by providing a central facility. shipped the first set of samples to the way, the archive has harmonised the To fulfil its scientific potential, it attracts Wellcome Trust Sanger Institute in 13 collections. researchers who want to collaborate with Hinxton, Cambridge, where they will the sample custodians.To achieve this, undergo extensive genetic testing.The aim The third step was setting up the DNA the DNA Network has now launched a is to identify genes that are risk factors Network itself. Initially the network was a secure website where researchers can for coronary heart disease – one of the forum for the sample custodians and examine data and jointly initiate project 13 serious human diseases being studied sample managers to exchange experiences, design with custodians through the in the UK DNA Banking Network (see box). but the focus now is on integration and network’s collaboration support service – making scientists aware of the benefits of the most advanced scheme yet for sharing Developing the Network using the resource, including opportunities materials and data in genetic epidemiology. The first stage of developing the network for collaborative research. involved collecting 40,000 blood samples How to apply for access from volunteer patients and from “We delivered our first large set of Researchers who would like to use the unaffected individuals.This work began samples for testing ahead of time and collaboration support service should first in 2000 was supported by £8m MRC to specification,” said Archive Director register with the UK DNA Network funding. It has involved 13 collections led Dr Martin Yuille.“This has strengthened website at www.dna-network.ac.uk.They by clinicians throughout the UK, to enable the collaboration – via the Wellcome will be sent a username and password study of the genetic causes of diseases of Trust Case Control Consortium – that will allow access to data and then to major public health importance.The between one of the collectors and a the service. Data on coronary heart funding provided the opportunity to major genotyping centre, the Wellcome disease are available now, and other data extend well-established studies – for Trust Sanger Institute.” sets will be rolled out in due course. example, the Acute Coronary DNA Event Library project, which already had support from the British Heart Foundation. Other Disease Principal Investigator collections were completely new, for Acute leukaemia Professor David Linch, University College London example the breast cancer collection. Alzheimer’s disease Professor Julie Williams, University of Wales Asthma and eczema Professor William Cookson, Oxford University Next, the MRC provided £2m funding for Breast cancer Professor Ellen Solomon, King’s College London Colorectal cancer Professor Harry Campbell, Edinburgh University the development of an archiving Coronary artery disease Professor Alistair Hall, Leeds University Medical School infrastructure to support the management Glomerulonephritis Professor Andrew Rees,Aberdeen University of the samples and data.The European Hypertension Professor Mark Caulfield, St Bart’s & Royal London NHS Trust Collection of Cell Cultures in Porton Macular degeneration Professor Alan Bird, Institute of Ophthalmology, London Down handles the blood, peripheral blood Multiple sclerosis Professor Alastair Compston, Cambridge University lymphocytes and EBV-transformed cell Parkinson’s disease Dr Carl Clarke, Birmingham University lines, and the Centre for Integrated Type 2 diabetes Professor Andrew Hattersley, Exeter University Genomic Medical Research at Manchester Unipolar depression Professor Peter McGuffin, Institute of Psychiatry, London University handles the DNA, with security 14 MRC | network Winter 2005/06 research roundup research roundup research roundup

Down syndrome mouse model Memories are made of this In a major step forward in stem cell technology, researchers have produced the first Until now scientists believed that mouse model for human Down syndrome. Funded by the MRC and the Wellcome structures in the brain’s medial temporal Trust, the research was led by Dr Victor Tybulewicz of the MRC National Institute for lobe (MTL) make up a single functional Medical Research and Professor Elizabeth Fisher of the Institute of Neurology, system that supports learning of new University College London. Down syndrome occurs in around one in every 750 memories, and is independent of other births. It is caused by having cognitive functions such as language and three copies of chromosome perception. However, a recent finding 21 instead of the normal two, from the MRC Cognition and Brain but scientists do not yet Sciences Unit in Cambridge has shown understand how the extra that not all parts of the MTL support the chromosome results in this same type of memory and some may have complex syndrome.To model a role in perception as well.This could the disorder, the team lead to improvements in tests for early manipulated mouse embryonic diagnosis of different types of dementia stem cells, by placing almost the and in rehabilitation of memory. whole of human chromosome The research was carried out with people 21 into the cells.They then who had suffered damage to different used these cells to generate a parts of the MTL.Those with damage to strain of mouse with the the perirhinal cortex had extreme additional human chromosome. difficulty in memorising objects with The researchers have shown, in several features in common, but showed collaboration with colleagues from the Institute of Cell and Molecular Science of normal learning with objects that looked Queen Mary’s School of Medicine in London, the University of Newcastle, King’s distinct from one another. As the amount College London and the MRC Prion Unit in London, that the new mouse strain has of information to be remembered was the problems with memory, brain function and the formation of the heart.These changes same, this result implies a difficulty with are very similar to those that occur in people with Down syndrome.“Aneuploidy is perception of the objects. However, seen in at least five per cent of all pregnancies,” said Dr Tybulewicz,“This technology individuals with damage limited to the will be a crucial genetic tool for investigating Down syndrome and other aneuploidic hippocampus performed normally.This disorders, in which individuals have the wrong number of chromosomes.” suggests that the hippocampus, long Science 309: 2033–7 thought to be the neural basis for memory, is not critical for memory of objects, but may play an important role in New hope for TB treatment? spatial memory and perception. Tuberculosis kills two million people each year. BCG, the only vaccination currently Journal of Neuroscience licensed, is not effective in the developing world; conventional treatments involve a 25: 10239–10246 lengthy period of combined antibiotics with significant side effects and multi-drug- resistant TB is on the increase.All of which means that new interventions are urgently needed.A potential immunomodulatory approach is in the offing now that researchers have found that high dose intravenous immunoglobulin (IVIg – human antibodies purified from plasma) has a greater effect in reducing the number of TB organisms than the bacille Calmette-Guerin vaccination.Their work showed that in mice high dose IVIg enhanced the immune response and produced a long-lasting 100-fold reduction in the numbers of TB organisms, in both the early and late stages of infection.

This reduction in TB organisms occurred after a single treatment cycle. However, it was lost in mice lacking Tcells – the white blood cells critical to the immune response against TB – which suggests that Tcells mediate the immune-enhancing effect of IVIg.The study, which took place at the MRC National Institute for Medical Research, was led by Dr Stephen Jolles of the University Hospital of Wales and funded by the MRC Technology Development Gap Fund. Further research in a clinical setting is now possible, as IVIg is already used for a range of autoimmune and inflammatory conditions and has an excellent safety record. Infection and Immunity 73: 6101–6109 Winter 2005/06 MRC | network 15 research roundup research roundup research roundup

Breathless excitement Around one in 10 asthmatics has the severe form of the disease, which often requires progressively high doses of steroids and is associated with a much higher risk of illness and death than milder forms. Research led by Professor Stephen Holgate at Southampton General Hospital has now uncovered a potential new approach to treatment, by blocking a powerful immune system chemical present in large amounts in patients with severe asthma. The team looked at the levels of tumour necrosis factor alpha (TNF alpha) in bronchial fluid and lung tissues samples from 26 people without asthma, 67 mild asthmatics and 51 severe asthmatics. Levels were significantly higher in those with severe asthma, and mostly concentrated in mast cells, the immune cells that play a part in the inflammatory reaction in asthma. In those with mild asthma or no asthma, levels were low.“This suggests that high levels of TNF alpha are characteristic of the more chronic form of asthma that is resistant to steroid treatment, rather than a feature of the disease itself,” says Professor Holgate.When 15 severe asthmatics completed a 12-week course of Etanercerpt, a drug that blocks TNF alpha's actions, all experienced a significant improvement in their symptoms. Thorax 60: 1012–1018 Extending the benefits of statins Statin drugs could benefit more people if targeted at all patients with diseased arteries, regardless of their cholesterol level.This was the finding of a collaborative study by scientists from the Clinical Trial Service Unit at the University of Oxford and the National Health Medical Research Council Clinical Trials Centre at the University of Sydney. Statins help to prevent heart attacks and strokes in high-risk patients, but most doctors prescribe them only when the blood cholesterol level is above a certain threshold, even in patients with narrowed blood vessels. HIV drug resistance high in UK This new study, involving more than 90,000 participants in 14 previously completed A study coordinated by the MRC Clinical trials, showed that many people with lower cholesterol levels could also benefit from Trials Unit has found that people infected statin treatment.The biggest benefits occurred in those with the greatest reductions with HIV in the UK have one of the in cholesterol after statin treatment, irrespective of their presenting cholesterol level. world’s highest rates of transmitted drug- Lead researcher Dr Colin Baigent said:“Doctors need to identify all patients at risk resistance. In 2,357 patients with the HIV of a heart attack or stroke, regardless of their blood cholesterol level, and then virus who had never received prescribe a statin at a daily dose that reduces their cholesterol substantially, which antiretroviral therapy before, 335 were would reduce the risk of a heart attack or stroke by at least one third.” resistant to one or more antiretroviral Lancet 366: 1267–1278 drugs. Of this group, 257 patients were resistant to one drug class only, 44 cases Youngsters go against the grain showed resistance to two drug classes and Young people in Britain are eating significantly lower amounts of whole-grain foods 34 showed resistance to all three than recommended, according to scientists at the MRC Human Nutrition Research commonly used drug classes. centre.This study provides the first insight into the amount of whole-grain eaten by Overall, there was a 14 per cent rate of young people – particularly pertinent given increasing awareness of the impact of resistance in the UK.The estimate is seven childhood diet on health in later life. Intake of a wide range of whole-grain foods was per cent for the USA, six per cent for estimated, using seven-day weighed dietary records from a national random sample France and 10 per cent elsewhere in of 1,583 young people aged 4 to 18 years who participated in the most recent Europe. Direct comparisons should be National Diet and Nutrition Survey in 1997. treated with caution, however, as different Although there is currently no UK Dietary Reference Value for whole-grains, the US studies have used different definitions of Department of Health and Human Services recommends three 16g servings per day. resistance. Nevertheless, this spread of Average intake among the young people studied was 7g of wholegrain per day, with resistance may begin to compromise the no difference between boys and girls. Less than a third consumed as much as 16g per enormous benefits of combination day.The main sources were breakfast cereals (56 per cent) and bread (25 per cent). antiretroviral therapy. It also highlights the A quarter of the young people studied were not eating any whole-grain foods at all. importance of early diagnosis and of health Those whose parents had a manual occupation were significantly less likely to education messages about safe sex. consume any. BMJ 331:1368–71 British Journal of Nutrition 94: 925–831 16 MRC | network Winter 2005/06

Inspiring the scientists of tomorrow Young people need to experience the excitement of science before stereotypical thinking about eccentric boffins starts to take hold.This is what MRC schools initiatives are helping to achieve…

Easily overlooked in the serious business valuable opportunity to convey important of science, young people are in fact a very general messages, such as why girls should important audience for the MRC.They think seriously about science as a possible represent the future generation of career and why animals need to be used medical scientists. Not only do we need in some areas of medical research. to make them aware of the importance of medical science in everyday life, we also The Science and Engineering Ambassadors need to inspire them with the possibilities scheme offers a slightly more formal way it offers for a future career. To help reach for researchers to get involved in young people and their families, the MRC communicating with schoolchildren. Run has become a familiar presence at the by SETNET, a UK-wide charity, the Edinburgh and Cheltenham science scheme aims to promote awareness of festivals. And during National Science Mr Jonathan Rees of the MRC Cancer Cell Unit science, technology, engineering and maths with Nuffield Bursary student Alice Firebrace week in March, many MRC researchers among young people bv providing present activities designed to appeal to schools.This can be as simple as a enthusiastic volunteers to work with young people, often through hands-on researcher approaching his or her child’s pupils and teachers in schools. involvement. school with an offer to hold an informal MRC-funded PhD students may be workshop in the science lab. Such an interested in the Researchers in Back to school encounter gives children a real insight into Residence scheme funded by Research Another very effective way in which the world of the scientist and often helps Councils UK and the Wellcome Trust – it’s scientists can communicate their research to inspire teachers with new ideas for ideal for those who would like intensive, to young people is through working in bringing science to life. It can also be a short-term involvement with schools. After a briefing day that includes ideas for The MRC National Institute for Medical Research runs an active schools activities with staff and pupils, participants engagement programme - Network takes a look at key activities spend an average of a week working in a secondary school. Each year the NIMR holds two school days, during which 320 to 360 Year 12 students from around forty local schools visit the Institute to hear talks on current research and see MRC scientists can also provide valuable demonstrations.Younger NIMR staff then lead discussion sessions during which the students can ask questions about science, careers and ethical issues. input into teachers’ understanding of medical science, through the professional Another highly successful annual event is the NIMR’s research summer school for Nuffield development programmes for teachers Foundation bursary students, attended this year by 16 students aged 17–18 from 11 provided by nine regional Science Learning schools.After a half-day induction course introducing molecular biology, lab skills and Centres coordinated by the DfES and the record keeping, they work with staff on projects for four to six weeks. Each student then produces a poster and report of their work and receives a Gold or Platinum BA Crest Wellcome Trust.Three new MRC Regional award for their achievements.The posters are later exhibited at Nuffield Foundation events. Communication Managers, and the existing In 2004, the Foundation selected two students to present their work, one at the Intel Science and Engineering Fair in Phoenix,Arizona and the other at the British Association Crest Science Fair. Nuffield Bursary recipient Alice Firebrace on her experience at the The NIMR’s work within schools ranges from occasional talks to involvement in the MRC Cancer Cell Unit: SETNET Science and Engineering Ambassadors scheme.The level of complexity can range “I found the work fascinating and everyone from a presentation on infections during a primary school assembly to an NIMR scientist was amazingly supportive and kind spending a week in a secondary school taking lessons. especially as it was entirely different from anything I had done at school. I contributed Staff also give talks about their research to sixth-formers, often as a result of volunteering to sequencing the p53 gene. I learned a lot through the Biology4all website. One NIMR researcher is a regular guest lecturer in about the theory behind the project, Imperial College London’s scheme aimed at ‘gifted and talented’ London children, which which as well as helping my understanding involves video-conferencing across a number of schools. of A-level genetics showed me how broad the subject of biology really is. I also learnt The Institute also holds an annual human biology essay competition for schools. It’s hugely to use the equipment for all the popular.The number of entries has doubled since 2003 – in 2005 there were 127 from 17 experiments, the methods and techniques schools. In addition to receiving a financial prize, the winner and two runners-up spend a to grow the cells, extract and replicate day at the NIMR visiting the labs and talking to scientists. their DNA and finally to sequence it.” Winter 2005/06 MRC | network 17

Bethan McDonald, an MRC-funded PhD student at King’s College London, tells of her experience as a Researcher in Residence:

After an introductory training day from the Researchers in Residence team, I was matched up with Langdon Park Community School, a mixed comprehensive secondary school in east London. I was Photograph courtesyAndy Buchanan of quite surprised at the level of responsibility Talking DNA at one of the MRC Virology Unit/Glasgow Science Centre workshops the teachers entrusted in me. Rather than just using me as a teaching resource and to Cambridge-based Manager, will strengthen and Technology) Awards encourage perhaps give some careers advice, they these links between MRC researchers and students aged 12 and over to develop were keen for me to give talks to the the Science Learning Centres. their scientific curiosity, problem-solving students and design practical lessons in line with the kind of experiments that I might and communication skills by undertaking do in the lab. Investing in young people science projects in school, some of which The MRC contributes just over £35,000 involve mentoring from industry or higher My research work involves investigating to RCUK’s investment in three main education institutions. The third scheme, the human proteins necessary for HIV-1 schools programmes.The first of these, the Researchers in Residence, enables around to be released from infected cells. I Nuffield Science Bursary scheme, provides fifty MRC PhD students per year to take decided to design some age-appropriate workshops on the immunology, the funding for talented sixth formers to their science into schools through week- transmission and prevention of HIV, and to work with professional scientists on long placements (see page 16 and box). give some ideas about current research projects in MRC laboratories. For and life as a scientist in a laboratory. example,Alice Firebrace of Ipswich High Future focus School, who worked with Dr Rebecca Over the past few years the MRC has I have previously been involved in a youth exchange project between Ghana and the Fitzgerald at the MRC Cancer Cell Unit in focused on secondary schools, where it UK, in which our group devised and ran an Cambridge on research into oesophageal was thought there was the greatest need HIV education programme with Ghanaian cancer (see box on page 16). The BA to stimulate interest and literacy in primary and secondary schools. I was Crest (Celebrating Creativity in Science science. But a recent OST report and a therefore able to adapt this approach, review by the Wellcome Trust has revealed which involved a presentation of the key ideas, followed by a playground/classroom Activities north of the border that children are being turned off science game and a question-and-answer session. even earlier, during their primary school In October 2005 scientists at the MRC I used a similar format when discussing current research and brought in Virology Unit, in partnership with Glasgow years.The MRC already makes efforts to equipment and consumables for the pupils Science Centre, ran a week of one-day reach and enthuse younger children, to touch and talk about. DNA workshops aimed at Scotland's through interactive presentations at Advanced Higher biology students. Ninety science festivals and projects such as Dr I spent 20–30 minutes in each lesson, so students from schools throughout Lizzie Burns’ very successful art-science that I could work with two classes per Scotland took part.The aim was to give workshops. It will now be focusing even school lesson time. In general the them hands-on experience of state-of-the more on imaginative, inspiring ways of response from the children was brilliant – art molecular biology techniques and the engaging all its young audiences, including lively, enquiring and very involved. One opportunity to talk with MRC scientists lesson on prevention and transmission of about their research and careers in developing further partnerships to add HIV with Year 10 pupils went so well it biomedical research. Participants value and scope to this important work. ended up taking the whole hour and the conducted a diagnostic experiment to students were still asking questions after detect virus DNA in mock patient samples the bell had gone! I was surprised and Find out more online using the polymerase chain reaction and impressed by what some of the students had learnt by the end of my time at the gel electrophoresis.They also looked at Science & Engineering Ambassadors Scheme school. DNA sequencing, interpreting the results www.setnet.org.uk of a sequencing experiment on a viral gene I became involved in the Researchers in and submitting the sequence to the NCBI Researchers in Residence Residence scheme because I hoped it blast server, to identify the virus and gene http://extra.shu.ac.uk/rinr/site would improve my confidence in public it came from.A lively debate on the ethical Science Learning Centres speaking, and develop my teaching and aspects of the human genome project www.sciencelearningcentres.org communication skills. I wanted to enthuse rounded off each day, giving everyone food Nuffield Science Bursary Scheme school children about science, because for thought.Teaching aids,reagents and the science is about questioning and www.nuffieldfoundation.org/go/ experimental protocols were devised by experimenting – skills that apply to all grants/scibsc unit staff in close collaboration with the types of learning. My placement was Science Centre education programmes BA Crest Awards challenging, but I really enjoyed working team, and the laboratory equipment was www.the-ba.net/Resourcesfor with the pupils. I feel I’ve learnt a lot and I funded by the Scottish Executive. Learning hope they did too. 18 MRC | network Winter 2005/06

Why IP is important to the MRC The potential health benefits of findings in basic science lie hidden until complex development work has been carried out.The concept of IP is vital to this translational process...

What is IP and why does it matter? by getting a fair return on their investment biotech and pharmaceutical industries An individual’s intellectual property (IP) and the MRC often benefits through and to protect and exploit the MRC’s IP. can be an invention, trade mark, original sharing in the revenues generated by The MRC uses MRCT to bring academic design, or secret knowledge used in the product sales.Any income the MRC research to the market through a practical application of a good idea. receives goes back into funding new process known as “technology transfer”, Intellectual property rights (IPR) are rights research, so the more it can earn through and has been leading biomedical granted through law, in the form of patents scientific findings, the more that can be technology transfer in the UK for many or copyrights, which allow ideas to be ploughed back into research. years. Patents are filed and licence formally transferred, sold or licensed. agreements are negotiated by MRCT on The generation and protection of IP allows If research is published without the MRC behalf of the MRC, with the primary aim the research that the MRC carries out in securing IP protection on an invention, of promoting the development of new its institutes and units to be used to then the research may be exploited and improved products in healthcare.The benefit society. without benefit to the UK or revenue commercial exploitation of new IP can going back to the MRC for further involve exclusive or non-exclusive How does the MRC use its IP? research. More importantly, for most IP licensing to an existing company, or to a Translating the MRC’s findings into tangible (which is usually at a very early stage in new start-up company. Start-up healthcare improvements often requires a any future product development), the companies may be created to develop massive investment.The MRC owns the IP incentive for a company to invest in new MRC technologies and inventions on findings (‘inventions’) by its scientific product development is greatly diminished where appropriate. staff, which enables the Council to restrict or lost if the IP has not been protected. who has access to these inventions, allowing it to entice one or more The role of MRC Technology Find out more online companies or public private partnerships In 2000 the MRC set up an affiliated Information on how MRC protects and (PPPs) to commit funds to the further company, MRC Technology (MRCT), as its uses its IP development of products. Society benefits sole agent acting to facilitate the transfer www.mrctechnology.org through new therapies, companies benefit of technology between the MRC and the

units centres institutes units centres institutes units centres

Vaccine institute expands

In November 2005 the Edward Jenner Biological Sciences Research Council, the programmes in veterinary and human Institute for Vaccine Research entered a Department of Health and vaccinology, for example in tuberculosis or new era by merging with the vaccine GlaxoSmithKline. Its scientific influenza, is an innovative approach that programmes of Oxford University and the programmes, led by Professor Peter should accelerate new vaccine Institute for Animal Health (IAH).The Beverley, have made important development in both areas. Institute’s headquarters will now be in contributions to many fundamental Oxford, under the directorship of aspects of vaccinology and the immune “This provides a unique opportunity to Professor Adrian Hill of Oxford University. response to infection. bring together a range of expertise in There will be a focus on human vaccine both human and veterinary vaccine development at Oxford and on veterinary The new partnership links this basic research and development to tackle some vaccines at the IAH and at the existing science with leading translational research of the greatest challenges to global health,” Jenner building in Compton in Berkshire. and vaccinology development programmes said Professor Hill. “With new recognition at Oxford University and at the IAH.The of the broader impact of poverty-related The Jenner Institute was established in Institute will cover the full range of diseases, the threat of bioterrorism and 1995 as the national vaccine research vaccinology research, from basic science to recent veterinary and human disease institute in a public-private partnership vaccine manufacture, clinical trials and field epidemics, vaccine development has never between the MRC, the Biotechnology and efficacy studies. Linking research been more important.” Winter 2005/06 MRC | network 19

Administrative Events diary

Efficiency Project The BA Crest Science Fair 2006 This annual event brings together winners of the BA In the last issue of Network we reported that the MRC’s Crest Award regional finals and 15–19 year-old self- Council had approved the business case for setting up a shared nominated students, all of whom have carried out services centre (SSC), to carry out a range of administrative outstanding science, processes for the MRC’s institutes, units and head office.The engineering and SSC project has passed some exciting milestones since then: the technology projects. MRC has appointed the Director and in late November 2005 For each of 13 took possession of the SSC offices in North Star House in regions throughout central Swindon. the UK, three Crest projects (Bronze, Silver and Gold) are selected to come to the BA CREST Science Fair. Phil Lambert, Director of the Judges select the best projects and young scientists for SSC, arrived in December a range of prestigious prizes, including cash and 2005 to take up his key role international trips. in establishing the centre and recruiting his team. During The BA Crest Science Fair in on 20 February 2006 at the last three years Phil was the Royal Society, London SW1. Director of the shared For further details, visit www.the-ba.net/ services centre for the ResourcesforLearning/BACRESTScienceFair TetraPak Group serving 65 businesses across Europe and Africa. FameLab 2006

When arriving at the MRC, This RCUK-sponsored national competition aims to Phil Lambert, Director of the MRC help scientists to develop their skills as Shared Services Centre Phil said:“Establishing a shared services centre is an communicators. Famelab is searching for the new faces enormous change programme for any business and will impact on of UK science who will be able to develop their ideas all of us in some way or other. I am very much looking forward and presentation skills for a TV audience. Regional to meeting everyone in the MRC and working with them to auditions are being held in March and April 2006 in Necastle, Swansea, Edinburgh, London and Belfast.Ten ensure that the programme is an unqualified success and that finalists will win a weekend masterclass in science together we create a service function of which we can all be communication, after which the final winner will be justifiably proud.” chosen at the Famelab final at the Cheltenham Science Festival in June 2006.The winner will receive £2,000 Preparing for arrival of staff and a development agreement with Channel 4 TV. Refurbishment work and installation of IT equipment is well under way and should take three to four months to complete. For further details, including audition dates, visit www.famelab.org The target date for the SSC to open its doors to staff is early April 2006.A schedule for the migration of services and staff to the centre is being developed and agreed with MRC units. MRC MRC units at the Cambridge Science staff can access the project plan through the MRC portal. Festival During National Science Week, MRC units will be The Finance and Human Resources work groups have completed holding a range of events at the Cambridge Science the process designs and validated these with MRC units through Festival. On 18 March there will be an ‘Ask a a series of workshops.This process information will be an nutritionist’ question-and-answer session with MRC essential part of SSC staff training and will also inform the units Human Nutrition Research at Michael House Café at as to the balance of responsibilities between them, MRC head 5.00pm.The Hutchison/Cancer Cell Unit is holding an office and the new SSC. open day and the MRC Cognition and Brain Sciences Unit will once again welcome the public to an Joint grant processing afternoon of presentations and practical The MRC and the other research councils have now agreed to demonstrations. Meanwhile, a new MRC event, Inner launch a project that would lead to establishing a joint processing Space – The Human Body, will explore the magic of unit for grants and fellowship applications.This is part of the metabolism at a central Cambridge venue. research councils’ policy of converging their processes wherever Further details will be available on the MRC website possible and introducing systems aimed at simplifying the by late January 2006. interfaces between research organisations and applicants. 20 MRC | network Winter 2005/06

MRC people

In September 2005 Professor November 2005. One prize went to Dundee Your feedback Sir Edwin Southern (top) University’s Division of Signal Transduction please and Professor Sir Alec Therapy – a unique consortium of 12 research Jeffreys were awarded the teams from the School of Life Sciences and the MRC Network is for Lasker Award for Clinical MRC Protein Phosphorylation Unit and six anyone who has an Medical Research at a leading pharmaceutical companies, to drive the interest in the work of ceremony in New York, in development of new drugs to combat major the MRC, including recognition of their pioneering diseases including cancer and diabetes. scientists, doctors and work in human genetic analysis. The other prize was won by the Centre for health professionals The Lasker Awards are often Brain Function and Development at Birkbeck, involved in medical referred to as “America’s Nobel University of London, for its work on brain research, government Prizes”. Seventy Lasker Award- function and cognitive development in the departments and winners have gone on to very young. The team includes MRC- funded parliamentarians, and receive the Nobel Prize, scientists Professor Mark Johnson, university staff and including 19 in the last 15 years. Professor Martin Eimer, Dr Gergely students.The aim is to Professor Southern invented the seminal Csibra, Dr Michael Thomas and Dr provide a quick, easy-to- ‘Southern blot’ technique for identifying DNA Fred Dick. read summary of activities sequences in the human genome while working across the MRC, from at the MRC Mammalian Genome Unit in In recognition of her research news through to Edinburgh in the 1980s. Professor Jeffreys’ MRC- contribution to cancer funding, grant schemes and funded work at Leicester University includes research, MRC-funded scientist policy issues, with pointers inventing genetic fingerprinting, which has Dr Kaye Williams has been to more in-depth revolutionised forensic diagnostics. awarded the British Association information on websites for Cancer Research/ and in other publications. The USA’s Society for AstraZeneca Frank Rose Young Neuroscience presented MRC Scientist Award for 2005. Kaye works in the We are very keen to Chief Executive Professor Experimental Oncology division of the Drug receive feedback on Colin Blakemore with its Action and Design Group at Manchester Network and suggestions Science Educator Award University’s School of Pharmacy and for new features from our in September 2005, at the Pharmaceutical Sciences. readers. So if you have any Society’s annual neuroscience comments, please let us conference in Washington DC.This annual prize In November 2005 Professor know. Just e-mail: is given to outstanding scientists who have made Cyrus Cooper and his team newsletter@ a significant contribution to public engagement at the MRC Epidemiology headoffice.mrc.ac.uk and communication about science. Resource Centre, Southampton, were Rheumatology Team of MRC Network is produced Two MRC research teams won the Queen’s the Year in the Hospital Doctor by the MRC Publications Anniversary Prizes for Higher and Further 2005 Awards celebrating clinical Team and is available in Education, at a ceremony at St James’s Palace in excellence and innovation in medicine. print and in downloadable pdf format at: www.mrc.ac.uk Infowatch

Wellcome Witnesses to Twentieth Century Medicine

This recent addition to the Wellcome Witnesses series looks at the development of short-course chemotherapy for TB, including work at Medical Research Council Professor Denny Mitchison's unit at the Hammersmith Hospital, the 20 Park Crescent advent of rifampicin and reappraisal of pyrazinamide, and MRC-funded London W1B 1AL large-scale trials in Africa, India, Singapore, Hong Kong and elsewhere. It includes transcripts of a seminar of experts involved in these advances, Tel:020 7636 5422 Fax: 020 7436 6179 organised by the Wellcome Trust Centre for the History of Medicine. Short-course Chemotherapy for Tuberculosis www.mrc.ac.uk Christie, D.A. and Tansey, E.M. (eds) (2005) The Wellcome Trust Centre for the History of Medicine £6 ISBN 0854841040 © Medical Research Council 2006