network Spring/Summer 2006 News, views and information from the Medical Research Council

In this issue Budget heralds radical new Flu science A look at the NIMR’s approach to UK medical research flu surveillance work health benefits:“This Budget confirmed vividly page 4 Gordon Brown’s commitment to research, especially medical research. It represents a real Biomarkers chance for substantial improvement for the workshop funding arrangements in the UK, facilitating the Will biomarkers interaction between basic and clinical research.” change the future Colin Blakemore observed that the Chancellor’s of medicine? announcement demonstrated his confidence in page 6 British scientists; also that his thinking is underpinned by figures from the OSI showing that Unit profile the UK now leads the group of the eight largest Network visits the industrial nations in its biomedical and pre-clinical MRC Protein research productivity. Phosphorylation “The UK’s record in supporting world-class Unit in Dundee Chancellor Gordon Brown delivers the 2006 Budget speech medical research through the MRC is second page 10 in the House of Commons on 22 March. to none. Developments in science can be Mind the found in every aspect of our daily lives Within the first few minutes of his 2006 Budget including breakthroughs on ageing and drug gender gap speech, Chancellor Gordon Brown made clear that research.The DTI is committed to ensuring How the MRC is science – in education and research – is central to that science and innovation are at the heart of helping women the Government’s plans for the British economy in the coming decades. One of his most radical government, and that we maintain the UK’s progress in science proposals was for a single fund of more than £1 leading position in medical research.We will page 14 billion ring-fenced for the MRC and for Department build on the outstanding achievements of the of Health (DH) R&D, to support the full spectrum MRC and ensure we are facilitating the National Science of biological and clinical research in the UK. How research base in the best possible way.” Week this new arrangement will work in practice is being Alan Johnson, Secretary of State for the Department A run-down of the determined through a consultation process chaired of Trade and Industry (DTI). events organised by Sir and steered by the Treasury and representatives of the DH and the Office of by MRC scientists Science and Innovation (OSI; the new name of the The importance of preserving the independence this year OST), which will be reporting back in the autumn. from government enjoyed by the research councils page 18 The MRC is keen to hear a wide variety of views to is recognised. Science and innovation investment help us develop our own contribution. Comments framework 2004-2014: next steps sets out the can be made through the MRC website (see box, Government’s vision for scientific research, Plus page 2). But formal submissions should be made recognising that funding must ensure “the Stem cell science, directly to Sir David’s consultation. continued delivery of world-class basic science, new faces, according to the long-standing Haldane principle research roundup, MRC Chief Executive Colin Blakemore welcomed which states that day-to-day decisions on research MRC people the Chancellor’s news. Integrating the two funding council scientific funding must be taken at arms- and more… streams could increase the speed and efficiency length from ministers. Funding would continue to with which basic research can be translated into be awarded on the basis of excellence across the >> page 2 2 MRC | network Spring/Summer 2006

<< The budget full spectrum of health research, from basic to clinical and public health.This will include continued support for investigator-led Backing new ideas in research”. clinical research Building on MRC success Experimental medicine is research that takes place at the Colin Blakemore’s hope is that the single fund will provide the interface of laboratory and patient-based studies. In recent opportunity to build on the MRC’s considerable achievements: years both the Government and the clinical research “We’re committed to supporting high-quality research across the community have drawn attention to the relative lack of entire spectrum of the biomedical and clinical sciences.We are investment in this area. In 2005 the MRC responded to these proud of our international reputation for achievement – from the concerns by making up to £15 million available for new introduction of penicillin and discovery of the structure of DNA research in experimental medicine.To help get a clear picture to the development of MRI; from the creation of blockbuster of how much funding was appropriate and where it was most antibody drugs to vital clinical trials, such as those on statins and on vaccines in Africa.” needed, the MRC invited ‘expressions of interest’ from the research community.These took the form of brief sketches The Budget statement emphasises the Treasury’s recognition of the which outlined the aims and costs of the proposed studies. crucial link between science funding and innovation. Colin Faced with almost 1,000 expressions of interest totalling Blakemore added:“Companies, universities and the public all over £350 million, the MRC Clinical Research Overview Group the UK are reaping the benefits of breakthroughs made by MRC- funded scientists.We are determined to expand that success even honed the call. Focusing on need and the best use of further. Combining the funding of the MRC and the DH will resources, it invited proposals that “evaluate a novel produce gains in efficiency and opportunities for collaboration that intervention, including an entirely novel application of an should benefit medical researchers throughout the UK.” already existing treatment in human participants with the aim to provide proof of concept.” Colin Blakemore says the MRC is looking forward to exploiting its strengths in biomedical research through continued close working In March 2006, the MRC with all the health departments, including those of Scotland,Wales awarded £15 million to and Northern Ireland.The organisation is keen to demonstrate scientists across the medical that it can respond quickly and effectively to clinical as well as research disciplines.The scientific challenges. successful applications ranged from research into the use of Developing UK science skills melatonin to reduce brain The Budget contained more good news for science in its damage in pre-term infants commitment to achieve a step change in the area of science and Blood cells infected by the and the effect of statins on the UK economy.The Government aims to create more science malaria parasite. asthma, to testing a malaria graduates and more science entrepreneurs.This chimes well with vaccine by using killer T cells against the parasite in liver cells. the MRC’s mission to sustain and develop the UK’s research capacity by training skilled scientists and supporting them at A huge boost for patient-based research, these awards will every stage of their careers. exploit the UK’s unique potential for such work. As the Government’s Next steps document points out,“few other The Next steps document points out the growing competition countries have a health service that provides researchers presented by China and India and emphasises “the need to adapt in with the potential to access virtually the entire population, order to continue to attract and retain high-value economic through an integrated system of primary, secondary and activities”. Anticipating this global scenario, the MRC is rapidly building its collaborations with scientists in China and south-east tertiary care.” Asia to ensure it can meet the health priorities and medical opportunities of the future, in the UK and around the world. Collective commitment

Find out more online The MRC’s £15 million investment in experimental medicine is part of a national strategy involving partners in the UK Single health research fund web forum Clinical Research Collaboration. Other initiatives include the http://extra.mrc.ac.uk/forms/shrf funding of new clinical research infrastructure by the Science and innovation investment framework 2004–2014: next steps ,The Wolfson Foundation and the Health www.hm-treasury.gov.uk/media/1E1/5E/bud06_science_332.pdf Departments, to which the MRC will contribute a number of Budget 2006 summary MRI scanners for use in experimental medicine studies. http://budget2006.treasury.gov.uk/ Spring/Summer 2006 MRC | network 3

Steps forward in stem cell science Following the International Stem Cell Forum’s meeting in January, Network brings readers an update on its work to establish and safeguard standards in stem cell science worldwide...

In January 2006 members of the International Stem Cell Forum challenging task of reviewing the differing ethical and regulatory (ISCF) gathered in Paris for their fourth annual meeting, which approaches of all countries that fund stem cell science, with a was chaired by MRC Chief Executive Colin Blakemore.Topics particular emphasis on research involving embryonic stem cells. ranged from progress in international collaboration and the Future work of the group will include developing a global register of Forum’s work on standardising characterisation of stem cell lines clinical trials involving therapeutic use of stem cells. worldwide, to its new online cell registry and cooperation between stem cell banks. The importance of ethics to stem cell research was brought into sharp focus when South Korean scientist Dr Woo-Suk Hwang Key ISCF projects admitted that he had falsified his research results. Dr Hwang Members were updated on two key ISCF working group projects – published papers in Science in 2004 and 2005 claiming that he had the International Stem Cell Initiative (ISCI) and a global review of created the world’s first cloned human embryos and 11 stem cell ethics and regulation of stem cell research. Led by Professor Peter lines tailored to individual patients.The Forum participants agreed Andrews of the University of Sheffield Centre for Stem Cell Biology, that this case emphasised the vital importance of oversight in the ISCI aims to develop internationally-agreed protocols for the science and of collaboration and open exchange between research culture and characterisation of human embryonic stem cells. teams worldwide to promote and maintain scientific integrity and Seventeen laboratories from 11 countries contributed a total of 65 transparency.The ISCF’s work, in areas such as the cell lines to its study, with the UK Stem Cell Bank playing a key role characterisation, banking, registration and exchange of stem cell in the collection and distribution of materials.The study aims to lines, looks set to speed the development of best practice establish whether the human embryonic stem cell lines created by guidelines for stem cell research. different laboratories around the world show similar properties.An initial review of the data collected indicates that the different lines do exhibit broadly similar properties.The Forum members also aim ISCF background to reach a consensus about a set of markers that can be used to The MRC launched the International Stem Cell Forum (ISCF) in define the traits and characteristics of human embryonic stem cells. 2003 along with eight other international funding agencies with In August 2005, 60 scientists from the 17 laboratories met with similar scientific principles, approaches and resources.These other key participants to review the data generated so far and to organisations all shared the MRC’s concerns about the need to discuss issues to be addressed.The ISCI hopes to be able to report create standardised worldwide criteria for creating, storing and the study results by early summer 2006. maintaining stem cell lines.The ISCF now has 19 participants from 17 countries, with China, Italy and the Californian Institute for All of the characterisation study data will be available in a searchable Regenerative Medicine the latest to join.The ISCF’s key principles online registry that is being developed in partnership with the MRC. and related activities include: The registry will hold a wide range of information for each of the 65 cell lines, including the ability of each to form tumours; pictures  and descriptions of any tumours formed when the cells are grafted Opposition to human reproductive cloning. into animals; details of culture conditions and feeder cells used;  Agreement with the use and sharing of both embryonic and microbiological summaries, and information about immunological adult somatic human stem cell lines. and genetic characteristics.  Belief that the creation of new human embryonic stem cell lines should be minimised. To build on the work of the ISCI, a second initiative is planned to  compare the effectiveness of the various types of culture systems Defining specific standards for the characterisation and that have been proposed for maintaining human embryonic stem registration of human embryonic stem cell lines. cells, and to examine the genetic stability of stem cell lines grown in  Working towards international harmonisation of ethical and different laboratories and under different conditions.A detailed intellectual property issues. proposal for this initiative will be presented to the Forum in May.

Mapping the ethical landscape Find out more online The global review of ethics and regulation is being carried out by the ISCF Ethics Working Party (EWP). Chaired by Professor Bartha For more information about the ISCF, its stem cell characterisation Knoppers of the University of Montreal, the group includes ethicists, study and the findings of its Ethics Working Party, please go to research scientists, clinicians and lawyers drawn from the Forum’s www.stemcellforum.org member organisations.Together they have undertaken the 4 MRC | network Spring/Summer 2006 Halting the spread of flu As the H5N1 flu virus spreads through bird populations across the world and the threat of a human pandemic looms, MRC scientists continue their vital work monitoring influenza viruses…

outcomes of their could change from primarily infecting birds work feed into to instead targeting humans. Firstly, its genes WHO could mutate over time. Or, if the H5N1 recommendations virus infected a human cell at the same as for new flu vaccines. an ordinary human flu virus, their genes could mix and give rise to a new Flu virus science ‘reassortant’ strain able to both transmit Influenza is a very from person to person and cause serious simple virus. Dr Alan disease. Scientists at the World Influenza Hay, director of the Centre look out for both of these things, NIMR World analysing samples to detect any differences Influenza Centre between the viruses infecting people and explained to Network those infecting birds. In recent months, they that there are three have been kept extremely busy urgently types of flu virus; analysing H5N1 samples from human cases types A and B cause in Turkey, Iraq, Egypt and Azerbaijan, as well major outbreaks as other countries with suspected cases. Dr Alan Hay with lab assistants analysing influenza virus samples. while type C causes only mild colds. From birds to people Most of us know what it’s like to have flu. H5N1, the strain of avian flu that is The haemagglutinin protein has two key But fewer people are aware that in 1933 currently spreading rapidly through bird roles: it binds the influenza virus to cells scientists at the MRC’s National Institute populations across the globe, is an influenza and infects these cells by fusing with them. for Medical Research (NIMR) were the type A virus. Like other type A viruses, it is It is the most important part of the virus first to identify the influenza virus. Fifteen defined by the haemagglutinin (H) and for immunity and therefore the target of flu years later the newly-formed World neuraminidase (N) proteins on its outer vaccines.An important part of WHO flu Health Organization (WHO) requested coat.There are 144 potential subtypes of virus surveillance is monitoring viruses that the MRC set up the World Influenza the influenza A virus, each with one of 16 from around the world for changes in the Centre at the NIMR.This reflected the types of haemagglutinin and one of nine haemagglutinin gene that might help the institute’s strength in flu science as well as neuraminidases. While most of these viruses to bind to human cells. If H5N1 the recent discovery that the virus combinations have been observed in birds, does become able to transmit between changes over time and the introduction of they don’t tend to affect people.“In fact, in people, detailed knowledge of the a vaccine. Since then NIMR scientists have the last century only three new subtypes haemagglutinin will help scientists to quickly been working tirelessly to increase of influenza A viruses mutated and spread determine the most suitable vaccine to use understanding of how the virus works and among people – and these caused the last to combat a pandemic. what can be done to combat it. three flu pandemics,” said Dr Hay. Scientists worldwide are becoming Other NIMR scientists are studying in Today the World Influenza Centre is one increasingly worried that H5N1 may cause precise detail how haemagglutinin binds to of four global WHO Collaborating the next human pandemic.Almost 200 receptors on cells and fuses with the Centres responsible for early detection of people have already been shown to be membrane of a cell it infects.They want to flu viruses with the potential to cause a infected through close contact with birds. understand what sorts of changes would human pandemic.These centres work And alarmingly, the virus has a very high enable the virus to switch from infecting alongside 112 institutions in 83 countries mortality rate, killing over half of the birds to targeting humans instead.“We’re which collect specimens and carry out people with confirmed infections. trying to understand the process of initial virus isolation and characterisation membrane fusion, including the way the work before shipping samples to the Influenza viruses are made up of eight molecule changes its shape to bring about Collaborating Centres for detailed individual genes.There are two ways H5N1 fusion,” Sir , director of the analysis. Each year World Influenza Centre scientists at the NIMR analyse around “ In the last century only three new subtypes of influenza A viruses mutated and 1,500 to 2,000 different human and animal spread among people – and these caused the last three flu pandemics.” flu viruses from about 50 countries.The Dr Alan Hay, Director,World Influenza Centre at the NIMR Spring/Summer 2006 MRC | network 5

Left: locations of amino acid variations in Centre scientists? As part of their vital influenza A haemagglutinin (HA) protein work monitoring flu viruses, they remain on which distinguish viruses isolated alert for the further spread of H5N1.And between 2004 and 2006 from human as they work around the clock to detect cases in: ● Vietnam and Thailand and combat any virus with the potential to ● Indonesia cause a human pandemic, it seems that we ● China are in good hands. ● Europe, the Middle East and Africa The black circles represent amino acids that are common to two of the four MRC support for lineages. Several of the differences are close to the receptor binding site and flu science may contribute to differences in immune response. The MRC spends £1.6 million each Diagram: Phil Walker, NIMR. year on flu research, predominantly through the programme at the MRC identified the structures of National Institute for Medical Research neuraminidases from a number of flu viruses.“This has shed light on led by Sir John Skehel and Dr Alan Hay. differences in the genetic However, in recognition of its key role determinants of resistance to in combating the threat of pandemic Tamiflu and Relenza by different influenza through funding further viruses,” said Dr Hay.The work research, the Council has allocated an relies on collaborations between virologists, biochemists, x-ray additional £10 million to this field over crystallographers and biophysicists. the next two years.To inform its A third protein found on the outer priorities and strategies in flu research, NIMR, told Network. His laboratory is coat of the flu virus is the M2 proton the MRC Infections and Immunity studying all 16 types of haemagglutinin that channel protein, which is involved in Research Board sent a scientific mission have been isolated from avian flu viruses. By ‘uncoating’ the virus and exposing its to Vietnam and China in November binding each protein to an artificial contents to the inside of the infected host receptor and working out its structure, cell. Dr Hay’s laboratory is particularly 2005, and in December 2005 it hosted they can gain vital clues as to how changes interested in M2, which is the target of the an international conference on in binding affect a virus’s ability to infect older antiviral drugs amantadine and “Pandemic Influenza: Maximising the birds or humans. rimantadine.While strains of H5N1 contributions of research”.This was isolated in Vietnam have been resistant to followed by a call for proposals at the Treatment targets these drugs, his team has found that they The other protein by which influenza A may be effective against strains isolated end of 2005.The MRC will make the viruses such as H5N1 are classified – more recently in other parts of the world. first awards in May 2006, focusing on neuraminidase – helps to release new Amantadine and rimantadine are less urgent research projects which need to copies of the virus from infected cells. expensive than oseltamivir and so might be in place before the next seasonal Like haemagglutinin, neuraminidase is also also be important in combating a human influenza months. In addition to crucial to WHO flu virus surveillance.This pandemic, particularly in poorer countries. standard research grants, funding is protein is the target of the antiviral drugs oseltamivir (Tamiflu) and zanamivir Continued surveillance available for international collaborations, (Relenza) and mutations in it can cause So in light of current media attention about workshops and travel grants for drug resistance. NIMR virologists and a possible flu pandemic, what does the researchers to and from the UK. protein structure scientists have recently future hold for the MRC’s World Influenza

Cooperative agreement with German institute signed

In February 2006, MRC Chief Executive Colin Blakemore and Two workshops will be held during the next year, one in and Professor Peter Gruss, President of the for the one in the UK.They will focus on molecular cell biology and brain Advancement of Science in Germany, signed an agreement to function and will aim to help young scientists set up collaborations promote cooperation between their two organisations.The between the two organisations.And under the agreement, exchange agreement aims to further scientific collaborations by promoting the visits will be organised to provide opportunities for junior scientists, exchange of researchers, experience and expertise, information and PhD students and administrative staff to spend time in their partner scientific findings. organisation’s environment. 6 MRC | network Spring/Summer 2006 Detective work A recent MRC conference explored the ways in which biomarkers could transform key areas of medical research. Network reports on the topics discussed…

Significant advances have been made during could be used. Founder of Biotrin the past few years in the fields of genomics, International, Dr Cormac Kilty, told proteomics and metabolomics.These delegates that his company is looking for advances have led to expectations that new novel biomarkers to detect tissue damage. ‘biomarkers’ might give us clearer insights These so-called ‘leaky’ biomarkers are into diseases and drug responses. On released from cells during the early stages 31 January, the MRC held a two-day of damage to organs such as the kidneys or conference entitled “Disease, drugs and pancreas. Dr Kilty explained:“A biomarker patient benefit – can biomarkers deliver?” must be highly specific to the tissue in The meeting aimed to identify how the UK question, it must be detectable, which can best contribute to research into means it must be accessible and it needs to biomarkers by capitalising on its be responsive. In other words it needs to infrastructure and scientific strengths. go up and down in response to damage and treatment.” So what is a biomarker? Biomarkers are biological characteristics Professor Paul Elliot of Imperial College that show what is going on inside a London spoke about the promise biological system. For instance, cholesterol biomarkers hold for monitoring disease and blood pressure have been used for progression and response to treatment in years as biomarkers of a patient’s epidemiological studies.“Classical cardiovascular risk. Professor Meindert epidemiology is focused on factors such as Danhof from the Leiden/Amsterdam Dr David Armstrong, chair of the MRC Health social class and lifestyle and how these Centre for Drug Research observed that Services and Public Health Research Board, sums up relate to diseases such as heart disease and the US National Institutes of Health the themes that emerged from the conference. cancer – without necessarily providing any Biomarkers Definition Working Group information about mechanisms,” he said. defines a biomarker as “a characteristic that monitoring of the progress of treatment,” Technologies such as genomics and is measured and evaluated as an indicator said Chief Executive Colin Blakemore when proteomics are now providing information of normal biological processes, pathogenic opening the meeting. Explaining that the about mechanisms. processes or pharmacological responses.” MRC is considering making substantial He added that “just about anything” funding available for biomarkers research, Dr David Armstrong, chair of the MRC’s relevant to the functioning of a biological he added:“We need to know what the gaps Health Services and Public Health Research system can be used as a biomarker. and opportunities are for the UK, where Board, suggested that biomarkers could be there is a niche for the MRC, how we can used as ‘surrogate outcomes’ in phase II The potential uses of biomarkers are capitalise on the strengths of the UK, clinical trials.This would make it possible to endless. Early detection and diagnosis of where the opportunities for partnership lie, reduce the number of patients and to get illnesses, prediction of a compound’s likely and what the likely impacts will be on answers more quickly than could be done toxicity, and insight into the body’s response human health in the short-, medium- by using clinical endpoints.“It seems to me to a drug are just a few of the possibilities. and long-term.” that biomarkers can be construed as Speakers at the meeting came from many another group of risk factors to join other medical disciplines, the pharmaceutical, “A biomarker is a characteristic that is things like lifestyle, signs and symptoms that biotechnology and diagnostic industries, measured and evaluated as an need adding to this risk paradigm. And if regulatory bodies and government.They indicator of normal biological we think about them in that way, the addressed issues ranging from biomarkers processes, pathogenic processes or kaleidoscope changes and we see them in a in drug discovery and experimental pharmacological responses.” slightly different light,” he said. medicine to their use in clinical trials and The US National Institutes of Health population sciences. Biomarkers Definition Working Group Since 2000 there has been a 10-fold increase in the number of published papers “Biomarkers research is recognised as being From leaky biomarkers to relating to the analysis of genes, proteins a promising area in clinical studies, in the biomarker signatures and metabolic processes, illustrating the development of new products, and in Throughout the conference, speakers gave rapid advances being made in these areas. clinical practice in the diagnosis and their perspectives on how biomarkers Dr George Orphanides of Syngenta told Spring/Summer 2006 MRC | network 7

participants that DNA chips can assess the branches of medicine, academia and action of 10,000 genes at once. For industry. Dr Sandy Kennedy from Brain example, they have been used to diagnose GlaxoSmithKline observed that companies and characterise diseases such as leukaemia could benefit from banding knowledge and sciences and predict patients’ risk of relapse. resources together in the search for and update Similarly, proteomics technologies can validation of biomarkers. differentiate the way certain proteins are As part of the Government’s 2002 expressed in patients and healthy Dr Lana Skirboll from the US National spending review, the MRC, the individuals. Dr Orphanides therefore Institutes of Health (NIH) agreed:“Strong Biotechnology and Biological Sciences Research Council (BBSRC), the suggested that the “real power” lies in partnerships and operational synergy Engineering and Physical Sciences biomarker signatures – assessing groups of between government, academia and Research Council, and the Council for biomarkers together and finding links with industry will be required.” The NIH has the Central Laboratory of the particular diseases. recently initiated an extensive biomarkers Research Councils were jointly research programme and has formed awarded £15 million to fund Biomarker challenges strong collaborations with many public and additional research into brain However, there are obstacles to overcome private sector partners.All of these sciences.As a result, 68 important before patients and clinicians can reap the partners are expected to bring different new projects were funded in 2003 benefits of further biomarkers research. Dr things to the table, from funding and ideas and 2004.This co-ordinated approach Steven Williams from Pfizer Global to access to patients for clinical trials, and to brain sciences is proving highly Research pointed out that there is a lack of lobbying power. effective as a springboard for exciting funding for research in the middle of the new research.To maintain the field, between the innovative basic science Talking points initiative’s momentum, representatives of these four research councils and leading to the discovery of biomarkers and To round off the conference, participants the Economic and Social Research industry-funded development and product discussed gaps and opportunities for Council (ESRC) met in November delivery. He outlined the high cost of biomarker development and came up with 2005 and identified new areas that biomarker development and validation, the ideas about how the MRC could contribute could benefit from joint funding, “rather haphazard” regulatory approval and what the UK’s niche might be. including neurobiology of mental process and a lack of standardisation of Dr Armstrong then summarised the main health and behaviour, computational markers that hinders their use in clinical themes of the meeting.The need for neuroscience and the interface trials.“Implementation is difficult because partnerships was again emphasised, as was between social science and standardisation does not seem to be the potential role of the MRC as an neuroscience. In March 2006 the MRC anybody’s business,” he said. Professor Ian ‘impartial broker’ in such collaborations. and the ESRC put out requests for Humphrey-Smith, from the Biosystems Also recognised was the need for innovative research proposals in the Informatics Institute, said that the quest for interdisciplinary training across molecular latter area (see highlight notice). Later validated biomarkers involves enormous biology, bioinformatics, mathematics and in 2006, the MRC and the BBSRC will hold evaluation workshops with the quantities of data and complex physical sciences. initial 68 award-holders, by which time mathematical analysis.There are 20 billion many should have produced potential binding sites for proteins in the Dr Armstrong pointed out that one of the interesting scientific findings. human body and 30,000 proteins.This UK’s major strengths is its large patient means that there is huge variance between populations, including the National Health Highlight notice: patients, who must be studied in enormous Service and several large population-based Society, social behaviour numbers to validate or qualify new study groups. He emphasised that and the neurosciences biomarkers.“Numerically the challenge is biomarkers research could capitalise on The MRC and the ESRC would like quite daunting, and the biomedical sciences these valuable resources, and that a to encourage innovative and must be increasingly mathematically driven,” coordinated approach to sample collection, multidisciplinary research proposals Professor Humphrey-Smith observed. and access to central databases, would be that link basic or health-related helpful. At the end of the conference there neuroscience to social factors and Joining forces was a consensus among delegates that the social behaviour. For further details Virtually all the speakers saw gap in the supply chain between the please visit www.mrc.ac.uk/strategy- collaborations as crucial for taking discovery and application of biomarkers call_soc_neuro.htm. biomarkers research to the next level. needed to be addressed and that a These could be across government potential MRC initiative could focus on the departments, research councils, different validation of biomarkers.

Find out more online

You can view a webcast of the biomarkers conference at http://clients.mediaondemand.net/mrc/ 8 MRC | network Spring/Summer 2006

Beam me up, Scotty

There is currently much excitement in the scientific community extremely bright light that can be used by BM14 to probe about the Diamond synchrotron being built at Harwell, which is due the structure of proteins, using a technique known as MAD – to open in 2007. So that UK structural biology researchers can multiwavelength anomalous diffraction.The MRC, the BBSRC continue to access beamlines in the meantime, the MRC and the and the Engineering and Physical Sciences Research Council Biotechnology and Biological Sciences Research Council (BBSRC) purchased BM14 in 2001 to provide the UK science community have allocated £1.7 million of renewed funding for the BM14 with a dedicated MAD-capable beamline. Recent steps forward beamline at the European Synchrotron Radiation Facility (ESRF) in include automating data collection from the beamline, Grenoble, France. ESRF is currently the brightest x-ray light source automated sample loading, sample tracking through the use of in Europe, with 40 beamlines including BM14. barcodes and management of the experiment by an intelligent and interactive database known as a Laboratory Information Synchrotron radiation allows scientists to probe the structure Management System. and properties of any substance, shedding light on areas as diverse as medicine, Today, UK structural biologists are tackling ever more complex materials science, biological questions. For instance, BM14 has enabled scientists to chemistry, geology, determine the structure of viruses, mammalian enzymes and an environmental science, array of other proteins important in human diseases. Investigators structural genomics and interested in using BM14 must apply for beamtime – proposals archaeology.A powerful are assessed by an independent review board, based on the magnet inside the quality of the science proposed. synchrotron bends high energy electrons that Find out more online are accelerated around For more information about BM14, please visit The European Synchrotron Radiation Facility a synchrotron ring – www.bm14.ac.uk/ where the BM14 beamline is housed. this generates

NPRI funds 26 disease prevention projects

In December 2005, 26 new research projects aimed at preventing approaches to encourage positive health behaviour, the projects cancer, heart disease and diabetes were funded by the National involve geographers, clinicians, dieticians, exercise scientists, Prevention Research Initiative (NPRI).The initiative is managed by statisticians, psychologists, economists and epidemiologists. the MRC and draws together a broad range of funding A second call for proposals has been agreed.This will have a organisations from the public and charity sectors (see box for very specific focus and more details will be published on the details).These organisations are working together to support high- MRC website in due course. quality multidisciplinary preventative research. Launched in October 2004, the NPRI has an initial budget of around £12 million over five years. Its committee includes scientific experts as well as members NPRI members of the public; the opinions of all committee members are taken into British Heart Foundation account when deciding which projects to fund. Cancer Research UK Department of Health Cancer, diabetes and heart disease are part of a worldwide epidemic in chronic disease that can often be prevented through Diabetes UK healthier lifestyles.To address this urgent global problem, the World Economic and Social Research Council Health Organization has set a goal of saving 36 million lives through Food Standards Agency prevention research and intervention over the next decade. Medical Research Council Research and Development Office for the Northern Ireland The NPRI’s first projects include research into discouraging alcohol Health and Social Services misuse and smoking and promoting physical activity and a healthy Chief Scientist Office, Scottish Executive Health Department diet.This work will take place in diverse settings including schools, Welsh Assembly Government homes, workplaces and doctors’ surgeries. Exploring a range of World Cancer Research Fund Find out more online The NPRI welcomes approaches from organisations For more information about NPRI , please visit that wish to join the consortium. For more information, www.mrc.ac.uk/index/funding-npri_details_2004.htm please email [email protected]. Spring/Summer 2006 MRC | network 9

New faces

At the beginning of 2006 the MRC Corporate Affairs Group previously worked in external relations at the Biotechnology and appointed four regional communications managers to provide Biological Sciences Research Council. support to units, centres and grant holders for their public engagement activities.The regional managers will be working closely The MRC has also appointed two new members of staff to work with our scientists on a number of different fronts including on clinical research strategy at head office. In addition to bringing promotion of their research through the media, working with a valuable academic clinical perspective to MRC decision-making, schools, advising on print communications and influencing local they will advise on ethics and governance issues relating to opinion formers. medical research.

Adrian Penrose is the Regional Catherine Elliot completed her clinical Communications Manager for Cambridge and training in obstetrics and gynaecology in the Midlands. He has 25 years of experience as a Edinburgh and London before becoming a communications and public relations clinical lecturer at . professional. Now based at the MRC She then went on to complete a Masters Epidemiology Unit at the Elsie Widdowson degree in Medical Law and Ethics and worked Laboratory in Cambridge,Adrian was the in medico-legal work and research ethics and communications manager at MRC Human Nutrition Research governance at the MRC Prion Unit before joining MRC head office. from 2001 to 2004. Joining Catherine is Helen Cope, who The Regional Communications Manager for trained in medicine at the University of Scotland is Pauline Mullin. Pauline has Edinburgh and pursued a career in spent 10 years with the Edinburgh academic psychiatry, specialising in International Science Festival and worked in neuropsychiatry. Before joining the MRC, communications at the Edinburgh Zoo and Helen spent six years in research management the Scottish Society for the Prevention of at the Wellcome Trust, latterly as head of the Cruelty to Animals. Most recently, she careers and clinical initiatives department. worked with a group of Scottish universities to set up and secure funding for business-academic projects.

Jude Eades, Regional Communications Opportunities Manager for the Oxford region, Southampton All applications must be costed on a full economic basis. and Bristol, comes from the National Blood Service (NBS), where she was responsible for Molecular and Cellular Medicine all aspects of public relations work, media Full application Peer Review Board Meeting* management and communication strategy for 31.08.06 Sept–Nov 2006 7–8.02.07 five NBS blood centres. Jude began her career Infections and Immunity at the London Evening Standard. Full application Peer Review Board Meeting* 7.09.06 Oct–Dec 2006 21–22.02.07 Sarah Hornby is the Regional Communications Manager for London. Before Physiological Systems and Clinical Sciences joining the MRC Sarah spent four years as Full application Peer Review Board Meeting* project manager in the Wellcome Trust’s Public 14.09.06 Oct–Dec 2006 27–28.02.07 Engagement Development Group. Prior to that, she worked on the Young People’s Programme Neurosciences and Mental Health at the British Association for the Advancement Full application Peer Review Board meeting* 21.09.06 Oct–Dec 2006 7–8.03.07 of Science, with specific responsibility for Science Year activities. Health Services and Public Health Research Another new face in the Corporate Affairs Full application Peer Review Board meeting* Group is Public Affairs and External 28.09.06 Nov 2006–Jan 2007 14–15.03.07 Communications Manager Simon Wilde. * Normal decision point Simon’s role involves increasing engagement between researchers and politicians, public MRC studentships - closing dates and patient involvement in research, and exhibitions and events. He comes from the Capacity Building Studentships August 2006 (date tbc) Industrial Collaborative Studentships August 2006 (date tbc) Hammersmith Hospitals NHS Trust, where he was the press and communications manager for research and development. Simon 10 MRC | network Spring/Summer 2006 Centre Profile: MRC Protein Phos The MRC Protein Phosphorylation Unit in Dundee leads UK research in the increasingly i look at the unit’s pioneering work, including its thriving collaboration with the pharmace

A generation ago, the world of science set up the Protein Phosphorylation Unit these pathways that are the best targets for knew very little of protein (PPU) in Dundee in October 1990, under new interventions. phosphorylation.The idea that protein the directorship of Sir Philip, who is a kinases and protein phosphatases might Royal Society Research Professor.The unit Achieving a balance be valid drug targets was remote, and employs over 100 people organised into Members of Dr Simon Arthur’s group are the suggestion that this area of science eight groups, covering a wide range of also exploring the inflammatory process, would become a major focus for research into this rapidly developing area. specifically the role of MAPKs, a particular investment would have been considered class of protein kinases.They have recently laughable.Yet today, it commands 27 per Watching the signals discovered that the protein kinase MSK cent of the pharmaceutical industry’s For the last three years, Philip’s own plays a critical role in controlling the annual R&D spending. research group has been focusing on the production of substances called anti- inflammatory proteins.As Simon explains: “Fine-tuning is all important. In the immune response, the balance between “I worked for 25 years on protein phosphorylation inflammatory and anti-inflammatory without any pharmaceutical company having the proteins is crucial. If they are out of slightest interest in my research.The situation today balance, diseases such as Crohn’s disease could not be more different.This shows yet again and psoriasis can occur.” This work could the importance of supporting fundamental research eventually lead to the development of drugs in new fields for a long period, given the length of which activate specific kinases to trigger an increase in anti-inflammatory proteins, but time that may be needed to tell whether it has without increasing inflammatory ones. therapeutic application.”

Sir Philip Cohen, Director, Protein Phosphorylation Unit Protein kinases that are mutated in inherited diseases Professor Dario Alessi’s pioneering research has provided “exciting new insights into Phosphorylation is now recognised as study of inflammation. Infection by a conditions such as cancer, diabetes and being one of the major ways in which pathogen triggers the activation of hypertension.” So said the judges when he cells coordinate their response to a wide networks of protein kinases, which leads to range of agents, such as hormones, growth the production of pro-inflammatory Protein phosphorylation factors, nutrients, cell damage and even cytokines (PICs).When released into the pathogens. Irregularities in blood, PICs stimulate other cells into Protein phosphorylation is the phosphorylation can cause, or be the action, which helps to mount an innate addition of a phosphate group (PO4) result of, major diseases including cancer, immune response to destroy the invading to a protein or small molecule.This diabetes, heart attack, hypertension and pathogen. Inflammation, however, is a reversible process is catalysed by rheumatoid arthritis.This makes protein double-edged sword: an over-reaction in two classes of enzymes, protein kinases and phosphatases of enormous the inflammation response can be as kinases, which add a phosphate, and importance as potential drug targets.An dangerous as no response at all, and this is protein phosphatases, which remove early success in this field was cyclosporin, a major cause of chronic inflammatory a phosphate. In this way the body can a drug launched in the 1980s. It diseases such as rheumatoid arthritis and switch proteins ‘on’ or ‘off’ as it suppresses the immune system by septic shock. Currently, the front line needs to.Around a third of the inhibiting a specific protein phosphatase treatments available are drugs which inhibit 30,000 proteins encoded by the first identified in 1981 in Sir Philip PICs, but they are expensive, require human genome contain covalently- Cohen’s laboratory at the University of repeated injections and only about a third bound phosphate.The ‘average’ Dundee, and is now widely used to of patients respond to them.A more protein kinase can add phosphates to prevent tissue rejection after organ effective treatment that can be taken orally around 20 different proteins and the transplantation. is urgently needed. However, researchers ‘average’ protein phosphatase must first understand the signaling pathways removes phosphate from around In response to growing awareness of the that control the production of PICs before 60 different proteins. importance of phosphorylation, the MRC they can identify the protein kinases in Spring/Summer 2006 MRC | network 11 sphorylation Unit, Dundee mportant field of protein phosphorylation. Network goes north of the border to take a eutical industry …

Gordon’s disease, an inherited hypertension syndrome. He has revealed that they switch on two other protein kinases, SPAK and OSR1, that play a critical role in regulating salt balance.These findings suggest that compounds which damp down the activities of WNK, SPAK and OSR1 could lead to new drug treatments for hypertension. Dario and his team are now looking at how mutation of the genes encoding the protein kinases PINK and LRRK1 cause early-onset Parkinson’s disease.

Protein phosphatases in diabetes and cancer Professor Tricia Cohen’s group is focusing on protein phosphatases, which remove rather than add phosphate from proteins. This is still a relatively unexplored area of The MRC Protein Phosphorylation Unit’s home in the Centre for Interdisiplinary Research at the University signal transduction compared to protein of Dundee. kinases.They use a multidisciplinary approach, including gene disruption in was awarded the European Molecular The breakthrough came when one day mammals and RNA interference Biology Organisation Gold Medal 2005, both teams compared notes and realised techniques in fruit flies. By expanding their widely regarded as the most prestigious that the cancer-linked enzyme LKB1 might investigation of the roles of protein research prize in Europe for a life scientist be the activator of the energy-controlling phosphatase complexes that are critical under the age of 40. kinase AMPK – a theory they went on to for human health,Tricia and her team verify.The next step for Dario Alessi was hope to identify targets for new drug Helped along by scientific serendipity, one to explore whether metformin, a drug treatments for cancer and diabetes. In remarkable discovery made by Dario’s used to treat type 2 diabetes by switching diabetes, they recently showed that the group was a breakthrough in on AMPK, might also help to treat cancer disruption of a mouse gene encoding a understanding how cells manage their because it mimics one of the actions of glycogen-targeted form of a specific energy ‘budget’.The team was the tumour-suppressor LKB1.A protein phosphatase can result in obesity investigating an enzyme, LKB1, which is preliminary epidemiological analysis and insulin resistance in later life. implicated in an inherited cancer carried out with clinical colleagues at the syndrome.Their aim was to work out University of Dundee Medical School As Tricia said:“Understanding the regulation which protein it phosphorylated, in the indicated that this idea was likely to be of the phosphatase which is targeted to hope that this would lead to an correct.This has encouraged Dario to glycogen is very important.A drug capable understanding of how mutations in the begin further trials on specific cancers in of altering its regulation may have potential gene encoding LKB1 cause cancer. collaboration with his clinical colleagues. for the treatment of diabetes, a disorder Meanwhile, Professor Grahame Hardie, a “The connection between AMPK and cell that affects 150 million people worldwide.” colleague working in diabetes research at growth could lead to some interesting Dundee University, was investigating a follow-up work,” he says.“If we can trick a Cellular secrets of flora and fauna different protein kinase,AMPK. Important cancer cell into thinking that it doesn’t Professor Carol MacKintosh and her in the control of energy levels in cells, have enough energy to divide, we may be group study plant and animal cells side by AMPK switches off energy-hungry able to stop it growing.” side, as they have much in common at a activities and switches on energy- molecular level. For example, the team generating processes when the supply is Dario has recently made an important found that C-shaped proteins called 14-3- low. Grahame was struggling to identify discovery about how mutations in the 3s prevent plants from suffering metabolic the protein kinase that activates AMPK. protein kinases WNK1 and WNK4 cause collapse in the dark.“I called it ‘cuddle and >> page 12 12 MRC | network Spring/Summer 2006

crunch – these responses to DNA is and well worth expanding further.” damage are regulated by protein kinases.” The unit also has interactions with other companies. For example, its long-standing The protein kinases in question bind to the collaboration with USA company Upstate damaged DNA and this activates other Inc led to the setting up of a new division kinases which, in turn, phosphorylate of Upstate in Dundee in 1999, which now proteins that protect genome stability and employs over 100 people. control repair.The challenge lies in pinpointing exactly how this control All for one and one for all mechanism works. If the group can unravel The PPU aims for a unified approach it, they may be able to develop an across its activities. It has a shared understanding of the mechanisms that are services division – with teams for DNA deregulated in cancer cells. cloning, DNA sequencing, antibody and protein production and cell culture – and Working with industry pools its funding from all sources so that In addition to excellent science, another of the money can be used strategically to the PPU’s great successes is its yield maximum benefit for the unit as a The 3-D structure of PDK1, a protein kinase collaboration with several of the world’s whole. For example, it has invested a discovered by Dario Alessi, which has become an leading pharmaceutical companies, large sum of money in state-of-the-art important target for developing anti-cancer drugs. including AstraZeneca, Boehringer mass spectrometers to identify Diagram: Daan van Aalten and Dario Alessi, PPU. Ingelheim, GlaxoSmithKline, Merck & Co phosphorylated sites in proteins – an Inc, Merck KGaA and Pfizer. Set up in area in which Dr Nick Morrice of the squeeze’ because that’s what the C- 1998, this is probably the largest PPU is a world expert – and in mouse shaped proteins seemed to be doing.They partnership ever undertaken between the genetics.“The unit is a pioneer in its bind to enzymes of sugar metabolism pharmaceutical industry and a UK field, and has developed a very efficient inside leaf cells when the sun goes down, research institution. It allows the way of operating,” Philip Cohen says. and through these actions help the plant companies to share the unit’s unpublished “Central budgets will never be able to to survive the night,” Carol explained. information, reagents, technology and fund everything we would like to do, and know-how and to have the first right to collaboration with industry helps to Following clues from their plant studies, licence the intellectual property generated. provide the additional funding needed.As the group looked at 14-3-3s in human a result, we’re working hard for both the cells and discovered that these help drive Over the past five years, income from the health and wealth of the nation.” cancer cells to scavenge for nutrients and venture totalling £15 million has been regulate how glucose is used to generate ploughed back into MRC research at the Future challenges cellular energy and growth. 14-3-3s have unit. But the collaboration doesn’t steer Thanks to the work of the PPU and its also given an unexpected insight into how the research – it is in fact the other way colleagues worldwide, the importance of viruses, for example HIV,hijack the internal round.And the benefits aren’t just phosphorylation to the body’s processes machinery of a cell.The next step will be to financial, as Philip Cohen explains:“For is now widely recognised. But this develop drugs that antagonise or enhance example, we gain access to company fascinating area of medical science will the functions of 14-3-3s inside cells. compounds that are valuable reagents for continue to challenge scientists for many our own research and our post-doctoral years to come, as Philip is quick to point Protein kinases and DNA damage researchers and PhD students get a great out:“The identification of the major The PPU’s most recent arrival is Dr John insight into the pharmaceutical industry; substrates of each protein kinase and Rouse, who came from the Gurdon many more go into industry as a result,” phosphatase is a major undertaking – and Insitute at Cambridge three years ago. His he explained.“The collaboration one that will take several decades to solve group is looking at how cells deal with happened almost by chance, but now it’s – but it’s at the heart of what we need to damage to DNA. Genetic material is established I can see what a good idea it know in the twenty-first century.” unstable and chemically reactive. If DNA damage is left unchecked, the sequence and the structure of the genome changes The PPU’s Mission and part of the instruction set is lost.This  To advance understanding of the role of protein phosphorylation and cell type of genome instability is seen in a large regulation in human disease. number of tumours.To prevent it, healthy  To facilitate the development of drugs to treat diseases caused by abnormalities cells are able to recognise and repair in this process. DNA damage.“Cells can launch a series of  To generate the reagents and improve the technologies on which more rapid events to ensure rapid DNA repair, and to progress in this area depends. ensure that damaged chromosomes aren’t  To train the next generation of scientists who will advance our understanding of replicated or segregated until they’re the subject. repaired,” John explained.“And here’s the Spring/Summer 2006 MRC | network 13

Administrative Efficiency Project on track

It is just one month before the launch of properly implemented.Training begins in the development of efficient common the Shared Service Centre (SSC), which is Swindon in May. processes for finance, HR and procurement an integral part of the MRC’s radical across the MRC. restructuring of the way it provides To allow adequate time for the new administrative support to its head office, processes to become established, the SSC A determination to provide highly institutes and units. programme will be rolled out to the professional, efficient and effective support various MRC units over a nine-month for directors lies at the heart of the SSC The build-up to the June launch is gathering period. Head office will be the SSC’s first programme. It will help ensure that the pace. Director Phil Lambert has recruited client, followed by the London Centre in MRC’s support processes and systems nearly all of his senior management team as July and the five Scottish units in August.All meet 21st century requirements and help it well as many of the key staff who will run units will be working with the SSC by to meet government targets for the Lyons the different functions within HR and spring 2007. and Gershon Reviews on administrative finance. All of the main finance team are on expenditure and regional relocation. And, board and HR is close behind. Providing an effective, responsive service together with cost savings generated by the with consistent processes, improved new procurement processes, the new Fitting out the new offices in Swindon was management information and cost savings is centre will ensure that an even greater completed on schedule by mid-April.At the an evolutionary process. Responding to proportion of the MRC’s financial resources same time, the team has been working with feedback from everyone within the MRC are focused on research. MRC units to draw up standard operating on the steps being taken is an important procedures and best practice guides which part of the project. Phil Lambert and his The SSC is building a platform that can be set out the optimum way for finance and team are developing a variety of scaled up to meet the needs of other HR to work once the SSC is operational.A communication routes to keep people up business both in and outside the MRC. The comprehensive training programme has to speed and ensure they know where to MRC is playing a full part in the discussions been designed for staff at the SSC and at go for information, including planning a all the research councils are having about the MRC’s units to make sure that these newsletter and poster campaign. Opening the most effective way to provide joint processes are clearly understood and the new office is an important milestone in shared services by the end of 2009.

research centre news research centre news research centre news

a healthcare revolution and our new Cambridge brain institute opens laboratory facility here in Sheffield will The MRC and the Wellcome Trust allow the Centre for Stem Cell Biology to have awarded Professors Trevor be among the first in the world to develop Robbins and Ed Bullmore a five-year stem cells for eventual use in medical grant of £4.8 million to set up the treatments.” The laboratory is currently Cambridge Behavioural and Clinical undergoing testing before it is granted Neuroscience Institute (BCNI).The Good Manufacturing Practice accreditation – Professors Bill Ledger, Colin Blakemore, Harry Moore award includes a significant a requirement for stem cells that will be and Peter Andrews at the opening. contribution towards the purchase of used to treat patients. New Sheffield stem cell lab a start-of-the-art 3T-MRI machine. In January 2006 the University of Sheffield Good news for endoscopy research The BCNI aims to increase opened a new MRC-supported A new suite with the latest endoscopy understanding of the functions of laboratory capable of producing equipment to diagnose and treat cancer, brain systems and networks and how embryonic stem cell lines that can be infection and inflammation of the lungs, they malfunction in neuropsychiatric used in medical treatments.The cutting- colon, oesophagus and stomach was or neurological disorders, which will edge facility is part of the university’s opened at the Addenbrooke’s Centre for enable clinicians to define patients’ Centre for Stem Cell Biology. It brings Clinical Investigation in February.The illnesses more accurately.The institute researchers a step closer to new Research Endoscopy Suite is a joint venture integrates research carried out by treatments for degenerative and chronic between the MRC,Addenbrooke’s hospital scientists at Cambridge University, conditions such as diabetes and and GlaxoSmithKline and is only the third the MRC Cognition and Brain Parkinson’s disease and to repairing of its kind in the UK. It will provide the Sciences Unit, the Wolfson Brain tissues after accidents or cancer.At the clinical infrastructure needed for collection opening, Professor Harry Moore said: and storage of clinical specimens with Imaging Centre and the Cambridge “Stem cell research is paving the way for linked, high-quality data. Centre for Brain Repair. 14 MRC | network Spring/Summer 2006 Mind the gender gap

Although more than half of the UK’s bioscience PhD students are female, only one in ten Network reports on the MRC’s ‘Women in Science’ initiative and how this is helping to rig

The UK’s thriving science, engineering and technology (SET) industries have a reputation for creativity, innovation and productivity. But to maintain our international competitiveness, the UK needs to increase the number of women being recruited to, remaining in and returning to SET occupations.Throughout the biological sciences a huge number of women leave between completing their doctorates and moving into senior positions.This picture is similar across Europe, the UK and within the MRC.The reported reasons for this ‘leaky pipe’ include indirect discrimination in the workplace, lack of confidence or self- esteem among female scientists, and the perception that the science environment MRC Chief Executive Colin Blakemore chats with Jane Butcher, of the UK Resource Centre for women in does not offer the flexibility women need science, engineering and technology. to balance a successful career with bringing up children. affecting women working in science. on exploring the issues surrounding women The subcommittee is made up of both in science, from the national and The UK Government has shown its support female and male MRC scientists spanning all international perspectives. It also looked at for minimising the gender gap in science. In career stages. In addition to exploring and the experiences of other SET organisations. its Science and innovation investment developing strategies to address the framework for 2004–2014 it set out key problem of the gender gap and retention of The third meeting, held in February this objectives of improving the under- early-career female researchers, it aims to year, saw members developing an action representation of women in science, improve opportunities for women to plan for shaping the MRC’s Women in technology, engineering and mathematics achieve their full potential as scientists.The Science priorities. First on the agenda was education and the workforce, as well as group is also charged with promoting a presentation by Jane Butcher of the UK increasing opportunities for professional change both by the scientists themselves Resource Centre (UKRC) for women in women working in SET. and also in the way in which research is SET, which was established to implement a organised and carried out. substantial part of the Government’s First steps strategy in this area.The centre will It’s important that the MRC plays its part in At this point the MRC Women in Science provide accessible, high-quality information bridging the gender gap. So in 2003 it initiative is focusing on piloting initiatives and advice to women entering, returning launched an initiative to address under- among postdoctoral scientists within units to and progressing in science. Jane gave an representation of women in science.The and institutes, after which the overview of the UKRC’s aims and first step was to establish a Women in subcommittee’s remit will be expanded to described some of the initiatives that it is Science Steering Subcommittee. Chaired by include other female research staff. funding and taking forward. Professor Ann Prentice, director of the MRC Human Nutrition Research centre in Taking action Next up was MRC Chief Executive Colin Cambridge, the subcommittee is finding At its first two meetings in July and Blakemore, who came to show his support ways to identify and address the key issues December 2004 the subcommittee focused for the Women in Science initiative. Colin stressed the importance of supporting and ‘The under-representation of women in science, engineering and technology encouraging diversity in science, including threatens, above all, our global competitiveness.’ its direct impact on the creativity and Baroness Susan Greenfield CBE, from SET Fair: A Report on Women in Science, competitiveness of science. Engineering, and Technology, 2003 Spring/Summer 2006 MRC | network 15

Introducing the Get SET Women Database make it to senior positions. The UKRC Get SET Women Database is designed to help increase awareness of women ht the gender imbalance… in science, by providing access to women working in SET industries who can be approached for promotional and work-related opportunities.These activities could include speaking at events, acting as role models, providing comment in scientific news Using our ASSETs coverage or sitting on public boards and committees. Subcommitte member Dr Helen Sweeting, from the MRC Social and Public Health Interested in getting involved? Sciences Unit in Glasgow, presented MRC To ensure the ongoing development of the database, the UKRC is keen to recruit female findings from the 2004 Athena Survey of scientists from all fields. New members are welcome whatever their career stage, from SET (ASSET).The survey explored the graduate to professor or director level. If you would like to get involved, please register now factors that influence male and female scientists’ career progression, aspirations at www.setwomenresource.org.uk. and expectations, as well as their ideas about what may obstruct women’s advancement in scientific careers.The findings highlighted differences between A tribute to Helen Muir (1920–2005) men and women in career aspirations, perceptions of equality in pay, promotions The first female member of and space at work, networking and wider the Medical Research Council, career development activities and guidance or support for career transitions.And the Professor Helen Muir died in survey made clear that many of the issues November 2005. Network pays that the MRC faces affect other research tribute to this talented scientist, councils and universities, so it can learn from these generic SET trends. who spent her life unveiling the secrets of osteoarthritis… Future plans To help the MRC move forward with its Born in India in August 1920, Helen Muir was schooled in Montreux, Switzerland and Women in Science initiative, the Newbury, England. She went on to study chemistry and biochemistry at Somerville subcommittee recommended a College in Oxford under the renowned scientist Dorothy Hodgkin, before beginning combination of approaches – ‘top down’ to her career in 1948 at the MRC’s National Institute for Medical Research, then in enable its findings to influence MRC policies Hampstead. In the institute’s Division of Biochemistry, Helen studied porphyrins under and processes, and ‘bottom-up’ to increase Albert Neuberger and Sir Stanley Peart. In 1954 she went to St Mary’s Hospital as Pearl awareness of the issue among staff, Assurance Arthritis Fellow, and there began her in-depth investigation of osteoarthritis. particularly those most affected.The A keen hunter, Helen studied osteoarthritis in the legs of her hounds during and after subcommittee is now identifying further their working lives. She also replicated the condition in laboratory beagles and studied steps that need to be taken. It realises that it in humans. In 1966 she moved to the Kennedy Institute of Rheumatology where she although there isn’t a ‘one-size-fits-all’ served as director from 1977 until retiring in 1990. solution, gradual improvement in MRC policies and practices will go a long way Helen Muir’s pioneering work established that osteoarthritis is not caused solely by towards increasing the number and age-related wear and tear of the cartilage in joints, but involves an active chemical enhancing the experience of women process with both environmental and genetic triggers.The MRC welcomed her onto working in science. the Council in 1973. She went on to serve on MRC committees in a number of areas, including finance, management of laboratory animals, and the selection of candidates for Find out more online the Pneumoconiosis and Toxicology Unit.

UK Resource Centre for women in SET: Many other honours followed. In 1977 Helen Muir became one of the first women www2.shu.ac.uk/nrc/index.cfm to be made a Fellow of the Royal Society, and in 1981 she was awarded a CBE. Athena Survey of SET: A feisty redhead, Helen had a great love of horse riding. But ironically, this caused www.uea.ac.uk/csed/resnet/crs_ her to suffer badly from spinal stenosis – a form of the osteoarthritis she spent her survey.htm life studying. 16 MRC | network Spring/Summer 2006 research roundup research roundup research roundup

Human energy mystery solved MRC scientists have unravelled one of the final puzzles in explaining how the body produces energy, with implications for understanding the ageing process and treating diseases such as Parkinson’s. Mitochondria are the ‘power stations’ inside cells that generate energy.The team, from the Dunn Human Nutrition Unit in Cambridge, has identified the structure of complex I – the fifth, most complicated member of the group of enzymes in the mitochondrial membrane that are crucial to this process. They found that the enzyme is assembled from many smaller proteins, which act as ‘building blocks’ and fit together as perfectly as pieces of a jigsaw puzzle.“One of the many new revelations from the structure is related to ageing,” said lead researcher Dr Leonid Sazanov.“We now know how elegantly different elements of the complex are arranged, so that electrons can be transferred through the complex with maximum effectiveness and minimal ‘leak’ into surroundings. If this leak were greater, more oxygen radicals would be produced, which can damage DNA and may lead to accelerated ageing.” Dr Sazanov and his colleagues believe that their findings may lead to ways to minimise further the production of damaging radicals, with implications for dealing with ageing. Science 311: 1430–1436 IQ and health inequalities Acting on impulse Many government programmes Many neuropsychiatric patients, particularly those with attention deficit hyperactivity aim to reduce health differences disorder (ADHD), have problems refraining from inappropriate actions such as between rich and poor. But for such blurting out impulsive comments or rushing in front of cars.A team of Cambridge interventions to be effective, it is University scientists has now shown that the ability to inhibit such actions is crucial that policymakers first controlled by the brain chemical noradrenaline.Their work, jointly funded by the understand the causes of health MRC and the Wellcome Trust, has implications for the development of new inequalities.A study by MRC scientists treatments for conditions such as ADHD.The participants were asked to press a left at the Social and Public Health Sciences or right key as quickly as possible in response to arrows on a computer screen. Research Unit in Glasgow has shown When a beep sounded, this signalled that they should cease doing so – a simplified that IQ may explain some, but not all, form of stopping that can be related to everyday behaviour such as being able to socioeconomic inequalities in health. stop at red lights.When participants were given atomoxetine, a drug that increases To test whether the relationship levels of noradrenaline, they were more successful at inhibiting their actions. Lead between health and socioeconomic researcher Dr Samuel Chamberlain, of the University of Cambridge School of Clinical position would disappear if IQ was Medicine, said:“These results are important because difficulties in stopping taken into account, Dr David Batty inappropriate behaviour cause some of the greatest problems for patients with and colleagues tested the IQ of over ADHD and their families.” 1,300 Scottish men and women in Science 311: 861–863 their 50s in 1987. Each participant’s socioeconomic status was assessed Work stress and the metabolic syndrome by a questionnaire and their health Stress at work has long been thought to increase the risk of heart disease, although was tracked over the next 17 years.As the mechanisms for this have been unclear. MRC-funded researchers have now expected, the poorest socioeconomic found that a person’s level of stress at work is directly linked to their risk of the groups were at the greatest risk of metabolic syndrome – a cluster of risk factors that puts people at danger of heart suffering ill health and dying early.Taking disease and type 2 diabetes.As part of the ongoing Whitehall II study, Dr Tarani account of IQ reduced this effect, yet Chandola and colleagues from University College London examined the relationship the risk among poorer people was between work stress and the metabolic syndrome in over 10,000 British civil still at least twice that of ‘advantaged’ servants aged between 35 and 55.They assessed the participants’ stress at work on people in half of the associations four occasions between 1985 and 1999 and measured components of the studied.The scientists concluded syndrome, including obesity, high blood pressure and raised cholesterol, between that IQ may not completely explain 1997 and 1999.The results showed that job stress was linked to the metabolic health inequalities between different syndrome, with a stronger association among men than women.The team suggest socioeconomic groups, but does that prolonged exposure to work stress may reduce biological resilience, thus contribute to them. disturbing the body’s physiological balance. British Medical Journal 332: 521–525 British Medical Journal 332: 580–584 Spring/Summer 2006 MRC | network 17 research roundup research roundup research roundup

A mammoth task Diabetes gene uncovered Scientists at the MRC Laboratory of Molecular Biology in Cambridge have Diabetes occurs when the insulin-releasing helped to invent a technique that has cracked the ancient DNA code of the cells in the pancreas stop working and woolly mammoth and established its evolutionary link with modern-day elephants. levels of glucose in the blood rise. Scientists The work was carried out in collaboration with scientists from the Max Plank have now discovered a gene called Nnt that Institute in Leipzig, Germany, University College London, the University of is involved in insulin secretion and may California in Berkeley, USA, and the Heinrich Heine Universität in Dusseldorf, prove key to treating diabetes.The team, Germany.The researchers are the first to have deciphered the complete DNA led by Professor Roger D. Cox from the sequence of the mammoth’s mitochondria. Mitochondria are the power houses of MRC Mammalian Genetics Unit at Harwell cells – tiny structures which process oxygen and turn food into energy. It is hoped and Professor Frances Ashcroft from that the technique will be of widespread use in analysing other ancient samples of Oxford University, found that the gene may DNA. Dr Paul Dear, whose group at the MRC Laboratory of Molecular Biology is play a role in removing free radicals – highly working to develop ways to analyse minuscule DNA samples, said:“When you reactive molecules with an unpaired have tools that let you look at single DNA molecules in this way, whole new electron that can damage living cells. horizons open up.” Funded by the MRC, the Wellcome Trust Nature 439: 724–727 and Diabetes UK, the researchers studied mice that lacked the Nnt protein and found A risky business that they had reduced insulin secretion and Risk-taking behaviour may be linked to a lower likelihood of developing glucose intolerance – early symptoms of Parkinson’s disease.This was the finding of a collaborative study by researchers at type 2 diabetes in humans.This led the the MRC’s Cognition and Brain Sciences Unit in Cambridge and their colleagues in scientists to think that a deficiency in Nnt London,Australia and the Netherlands.The scientists found that people who protein may result in an increase in damage develop Parkinson’s disease are less likely than people without the disease to to the insulin-releasing pancreatic cells by smoke, drink a lot of alcohol or have a high caffeine intake.To explore whether free radicals and, consequently, reduced this link is due to personality characteristics, the researchers compared 106 insulin secretion.“It seems very likely that patients with Parkinson’s disease with 106 healthy people. Both groups filled in Nnt is important for insulin secretion in questionnaires about their personality traits and behaviour, as well as their humans,” said Professor Cox.“That would smoking and drinking habits and caffeine consumption.The Parkinson’s patients open up exciting possibilities for treating had lower levels of risk-taking and ‘sensation-seeking’ behaviour and higher levels type 2 diabetes. It may even turn out that of anxiety and depression.They tended to spurn openly hedonistic activities and defects in Nnt can cause human type 2 be scrupulous, socially withdrawn, inflexible, disinclined to take risks and relatively diabetes.” Professor Ashcroft added:“If we passive.The scientists suggest that the apparent protective effect of smoking and understand how insulin secretion is high caffeine and alcohol intake against Parkinson’s disease may be because people controlled, then we may be able to who are more likely to take risks may also be more likely to have these habits. intervene to restore secretion in patients with diabetes.” Journal of Neurology Neurosurgery and Psychiatry 77: 317–321 Cell Metabolism 3: 35–45 18 MRC | network Spring/Summer 2006 Science for all Each March, National Science Week celebrates science, engineering and technology and their impact on our everyday lives. Network reports on MRC activities during this year’s event…

Innovation Minister Lord Science across the airwaves Sainsbury present, the audience Broadcasting across Oxfordshire and heard five “outstanding young adjoining counties, BBC Radio Oxford researchers” talk about attracts tens of thousands of listeners their work.These speakers each day. During National Science Week included Dr Danielle Turner, an the station launched the Oxford region’s MRC-funded postdoctoral “MRC scientists on the air” project, which researcher in the University brought MRC scientists into the BBC of Cambridge’s Department studios to talk on research-related topics of Psychiatry, who spoke about in the Oxford area. Chief Executive Colin the science of cognitive Blakemore was first up, talking to enhancement.“I really enjoyed afternoon presenter Bill Heine about the the challenge of communicating value of the week in helping to promote Students carrying out DNA experiments at Villiers Park. the excitement and relevance of science, and the MRC’s mission to National Science Week enables people of my work,” commented Danielle. communicate its work to the public. all ages to find out more about science and to meet some of those responsible At Westminster Dr Chris Mee (MRC Dr Lizzie Burns visited BBC Radio for making the UK a world leader.And Functional Genetics Unit) and Richard Berkshire to talk about a series of art- because the approach is informal and Page (University of Cambridge) won science workshops she was running on interactive, the experience is fun.This year first prize and the Westminster Medal behalf of the MRC in Reading. Held at the there were MRC events for all ages, from in a competition of 160 posters at city’s Museum of Rural England, the schoolchildren to local radio listeners and the annual Science, Engineering and workshops had the theme of ‘Bringing parliamentarians.At the National Institute Technology for Britain reception at the colour to life.’ Over four days, Lizzie took for Medical Research (NIMR) in north Houses of Parliament.Their presentation Reading school students and local London, researcher Clare Davy organised was on “The Alzheimer’s fly:A model residents on a microscopic journey an afternoon of workshops for sixth- organism for the study of Alzheimer’s through the body.After showing them formers, including arts students. disease.” colourful molecular and cellular images, Participants explored the science and issues behind the current development of a cervical cancer vaccine, moving around different stations where they could interview scientists, listen to presentations, or discuss ideas.“As well as looking at the science of virology and immunology, the event also focused on communication of science and the wider ethical and social issues of research,” explains Clare.“Interestingly, it was the non-biologists who unanimously agreed that the best part of the workshop was interviewing the science experts!”

Science in Parliament Meanwhile the Royal Society and the Office of Science and Innovation held a morning event celebrating British science for parliamentarians and policymakers.With Alan Johnson, Secretary of State for Trade and Industry and UK Science and ‘Bringing colour to life’ workshop at the Reading Museum of Rural England. Spring/Summer 2006 MRC | network 19

Events diary Cheltenham Science Festival The MRC will once again be presenting a series of events at the annual Cheltenham Science Festival: a hands-on interactive family exhibition in the festival’s Discover Zone, based on MRC science and manned by MRC researchers; a science-art event run by Dr Lizzie Burns, and principal sponsorship of an Sixth-form students at the NIMR taking part in workshops. Dr Danielle Turner at the Royal Society. event on ageing with Professor Raymond Tallis. she encouraged them to create their own Powles-Glover from MRC Harwell to host The festival takes place from artworks inspired by what they’d seen. a working visit by 22 students at Villiers 7 to 11 June 2006 in various She was supported by MRC scientists Park Educational Trust.The students spent locations across Cheltenham. from the Mammalian Genetics Unit at a day carrying out DNA experiments – More information is available at Harwell, including Paul Denny, group using computer graphics, microscopy and www.cheltenhamfestivals.com. leader of Infection Genetics, and protein crystallization – and experiencing Charlotte Dean, programme leader in work in a lab first-hand. Everyone involved MRC Open Public Developmental Genetics. had a busy and thoroughly enjoyable day, Council Meeting As part of the MRC’s which received top marks from students commitment to openness, Open days and visits and teaching staff! To round off the MRC’s transparency and dialogue with Also from the Mammalian Genetics Unit, Cambridge activities, early-career scientists our stakeholders, the MRC’s Cathryn Tambini ran a workshop at St from the MRC Cognition and Brain Council will be holding its Amand’s Primary School in East Hendred, Sciences Unit showcased their research in second open meeting on Oxfordshire. Entitled “How clean are our ‘Exploring mind and brain’ to a ‘sell-out’ 27 July in London.This a great hands?”, the event was part of the school’s audience.All the scientists involved felt this opportunity for members of the Health and Fitness Week. Professor Doug year’s Cambridge events were very public and other stakeholders to find out more about the MRC, Higgs, Director of the Molecular worthwhile and are already talking about including a recent MRC/BBSRC Haematology Unit in Oxford, gave a talk on activities for 2007. public consultation into research the DNA revolution to sixth formers at priorities in ageing. Sutton High School for Girls, while Hungry for knowledge For more information, visit colleague Dr Marella De Bruijn spoke The Cambridge Science Festival also www.mrc.ac.uk. about ‘Haemopoietic stem cells in biology takes place in March – the week after and disease’ as part of an evening of free National Science Week – and this year Launch of public lectures in Oxford.The Weatherall drew huge crowds of all ages. Researchers BBSRC/MRC ageing consultation report Institute of Molecular Medicine hosted a from the MRC Dunn Human Nutrition Since March the MRC and the knowledge-sharing day including lectures Unit and the MRC Biostatistics Unit Biotechnology and Biological and a poster exhibition, and scientists at the hosted ‘Inner space’, an interactive Sciences Research Council have MRC Anatomical Neuropharmacology Unit exhibition which described the magic of been running a public welcomed secondary school students from metabolism from mitochondria to consultation on priorities in around the country to its open day. Pupils muscles.The star attraction was an ageing research.The MRC will aged between 14 and 18 toured the unit’s exercise bike with a difference, created be announcing the results and laboratories, met scientists and helped to by scientists and built by technicians in next steps at its open council meeting on 27 July. carry out experiments such as ‘patch- the MRC workshop. Hundreds of visitors More information will be clamping’ a brain cell. used the bike to ‘work out’ for available nearer the time at themselves the relationship between food www.mrc.ac.uk. In Cambridge, the Hutchison MRC intake and energy expenditure, and a full- Research Centre/Cancer Cell Unit hosted length model gut allowed younger visitors BA Festival of Science an open day on the theme of ‘Making a to get to grips with digestion. Later that The MRC will once again take part in the BA Festival world of difference’.This explored day, a packed audience at the Michael of Science, which will be held cancer’s impact worldwide and how House Café in the centre of Cambridge this year in Norwich from lifestyle influences our risk of developing posed their diet and nutrition questions 2 to 9 September. cancer.And at the Laboratory of to a panel of scientists from the MRC More details are available from Molecular Biology, Dr Samantha Wynne Collaborative Centre for Human www.the-ba.net/festivalofscience. and colleagues teamed up with Dr Nicola Nutrition Research. 20 MRC | network Spring/Summer 2006

MRC people

Professor Veronica van Public Health Sciences Unit in Glasgow, and Your feedback Heyningen has been awarded the Professor Ian Dreary at the University of please 2006 European Society of Human Edinburgh were ranked 24th by Discover in its top Genetics Prize for contributions to 100 achievements of 2005. By measuring the IQs MRC Network is for international human genetics and reaction times of 898 people in their 50s in anyone who has an research.At the award ceremony in 1988 and recording which of them had died by interest in the work of Amsterdam in May 2006, she gave a lecture entitled 2002, the scientists revealed a relationship between the MRC, including “Making eyes: lessons from genetic ocular lower IQ and early death. scientists, doctors and malformations”. Professor van Heyningen joined the health professionals MRC Human Genetics Unit in 1977 (then called the In March 2006, two MRC scientists involved in medical Clinical and Population Cytogenetics Unit), where received Wolfson Research Merit research, government she now heads the Medical Genetics section. Awards. Professor Avshalom departments and Caspi, of the Institute of Psychiatry parliamentarians, and Dr Christopher Mee has been at Kings College London was university staff and hailed as one the UK’s top young awarded the prize for his research students.The aim is to scientists after being awarded the into genetics and stress, while provide a quick, easy-to- Westminster Medal for his work on Professor Jane McKeating, read summary of activities “The Alzheimer’s Fly:A model of the University of Birmingham across the MRC, from organism for the study of was recognised for her research research news through to Alzheimer’s disease”. Dr Mee, of the MRC into how the hepatitis C virus funding, grant schemes and Functional Genetics Unit in Oxford, was awarded infects the liver. policy issues, with pointers the prize at the annual Science Week reception at to more in-depth the House of Commons in March. Martin Wood has recently retired information on websites after 30 years’ service with the and in other publications. Two MRC-funded studies were among 2005’s top MRC and MRC Technology. During achievements in prestigious science magazines. that time, he has been instrumental We are very keen to Professor David Porteous and colleagues at the in intellectual property and licensing receive feedback on University of Edinburgh worked with scientists at activities around humanised Network and suggestions the University of Glasgow and the pharmaceutical monoclonal antibodies, which have for new features from our company Merck, Sharp and Dohme Ltd to identify a generated around £200 million in royalties for the readers. So if you have any gene interaction that increases the risk of mental MRC. Martin has also contributed to the foundation comments, please let us illness.The team’s paper was ranked by Science as of many spin-out companies. We would like to take know. Just mail: the fifth most important “breakthrough of the this opportunity to thank him for all his efforts and newsletter@ year”. Similarly, Geoff Der, at the MRC Social and wish him a long and happy retirement. headoffice.mrc.ac.uk MRC Network is produced by the MRC Publications Team and is available in Infowatch print and in downloadable Testing Treatments: better research for www.dana.org/cerebrum pdf format at: better health care Cerebrum:The Dana Forum on Brain Science is www.mrc.ac.uk How do we know whether a billed as “the journal of opinion about brain particular drug, therapy or science that can change your mind.” It operation really works? How focuses on issues raised by brain research, reliable is the clinical evidence? Is their impact, and their implications, such as current research fully focused on how brain science affects our health and the the real needs of patients? These choices we make every day. From January Medical Research Council and other thought-provoking questions are 2006, Cerebrum became a free 20 Park Crescent dealt with in this probing inquiry into modern web-only publication London W1B 1AL clinical research. Testing Treatments was written with monthly articles, by Sir Iain Chalmers, coordinator of the James features, letters to the Tel:020 7636 5422 Fax: 020 7436 6179 Lind Initiative, Imogen Evans, Clinical Research editor and a complete and Ethics Liaison Manager at the MRC from searchable archive of all www.mrc.ac.uk 1996 to 2005, and Hazel Thornton, advocate print issues from 1998 for public involvement in medical research. to 2005. © Medical Research Council 2006