Medical Research Council2001年年度報告.pdf

1、Medical Research CouncilMRC ANNUAL REPORT2000 2001 Medical Research Council 2001Published by The Medical Research CouncilHead Office20 Park Crescent,London,W1B 1ALTel:020 7636 5422Fax:020 7436 6179Web:www.mrc.ac.uk20.00 netISSN 0141 2256Layout and Design:Fatima de AbreuPrint and Reprographics:Warwic

2、k Printing Company Ltd.(Tel:01926 491 666)Photo credits:Graham Clark(Page 46)MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 2001In accordance with Schedule 1 to the Science and Technology Act 1965,the Medical ResearchCouncil(MRC)submits the following report on its activities from 1 April 2000 to 31 Mar

3、ch2001.In submitting this account the MRC wishes to pay tribute to the work done by its ownstaff and by all other staff it supports.It also wishes to express its gratitude for all the adviceand assistance received from those parties consulted in an individual capacity and frommembers of boards,commi

4、ttees and working parties.Sir Anthony CleaverProfessor Sir George RaddaChairmanChief ExecutiveMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 20013PREFACEthe CouncilThe Councils mission is set out in our Royal Charter:in summary MRCs purpose is:To encourage and support high quality research with the aim

5、 of maintaining and improving human health.To train skilled people,and to advance and disseminate knowledge and technology with the aim ofmeeting national needs in terms of health,quality of life and economic competitiveness.To promote public engagement with medical research Sir Anthony CleaverChair

6、manProfessor Sir George RaddaChief ExecutiveProfessor JI BellUniversity of OxfordDr Peter FellnerCelltech Group PlcProfessor L DonaldsonDepartment of HealthProfessor Ian MacLennanUniversity of BirminghamProfessor RM DentonUniversity of BristolProfessor R FitzpatrickUniversity of OxfordProfessor R Mi

7、rskyUniversity College LondonMr D FlintDirector of Alliance and Leicester InsuranceProfessor E JohnstoneRoyal Edinburgh HospitalProfessor N RothwellUniversity of ManchesterProfessor G RichardsonQueen Mary and Westfield CollegProfessor Sir John PattisonDepartment of HealthSir Ross BucklandUnigate plc

8、Mr MJ Earwicker(Office of Science and Technology)Representing the Secretary of State forTrade and IndustryThe Council members 2000-20014FOREWORDfrom the Chairman and Chief Executivep pa ag ge e 3 3ACHIEVEMENTSscientific achievementsp pa ag ge e 5 5RESEARCHother researchdevelopmentsp pa ag ge e 1 19

9、9PARTNERSHIPSkey partnershipsp pa ag ge e 2 25 5PEOPLEdeveloping first rate peoplein medical researchp pa ag ge e 3 37 7TECHNOLOGYcommercial exploitationp pa ag ge e 4 43 3PUBLICpublic engagementp pa ag ge e 4 47 7PRINCIPLESethics and businessprinciples in themanagement of researchp pa ag ge e 5 51

10、1FRAMEWORKthe financial frameworkp pa ag ge e 5 55 5CONTENTS12345678MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 20015and of its subsequent contribution to health andwealth.Over 200 companies are now marketing ordeveloping research,diagnostic or therapeuticmonoclonal antibody applications.A key theme

11、 in this years Report is the range ofMRC investments and initiatives which are beingdeveloped in partnership with others.Jointworking with other research councils has beenpursued with vigour as shown in chapter 3.Research Funders Fora in ageing,heart diseaseand cancer are bringing a range of interes

12、tstogether working for the common good onthese major areas of public policy and interest.Finally,we would like to express our thanks tothe network of individuals who continue to giveof their time to corporate strategy developmentand implementation,through our Boards andother committees.They have bee

13、n joined thisyear by two new groups.These are the MRCTraining Board which is developing a strategy forall our investment in training and careers both inMRC Units/Institutes and in the universities,andthe MRC Consumer Liaison Group whichadvises Council on how best to involveconsumers in the work of t

14、he MRC.FOREWORDfrom the Chairman andChief ExecutiveThis has been a momentous year for science.The announcement earlier this year of thecompletion of the full sequence of the humangenome brought home,even to many who hadnot thought in such terms before,the hugeopportunities which genetics research of

15、fers forhealth care in this new century.This endeavourhad its roots in MRC support for the very earlydays of sequencing under Fred Sanger at theMRC Laboratory of Molecular Biology inCambridge in the late 1970s and 80s.Furthergroundwork was laid through MRC supportedwork on sequencing the nematode wo

16、rm underJohn Sulston in the 1990s.The completion ofthe sequence was reported in last years AnnualReport.Another significant reminder during the year ofthe importance of long-term support forscience from which society can reap the ultimatebenefits,was the 25th anniversary of thediscovery of monoclona

17、l antibodies.Dr CsarMilstein(pictured right),also from the MRCLaboratory of Molecular Biology in Cambridge,was awarded the first MRC Millennium Medal inrecognition of this Nobel prize-winning workSir George RaddaChief ExecutiveDr Csar MilsteinFirst MRC Millennium Medal winnerSir Anthony CleaverChair

18、manMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 20017THE YEARS SCIENTIFIC HIGHLIGHTSACHIEVEMENTSscientific achievements1A small selection from last years many noteworthy MRC-funded scientific achievements:PEOPLE AND POPULATION STUDIES:HEALTH SERVICES AND HEALTH OF THE PUBLICAntisocial and aggressive

19、behaviours are common in children and may lead to difficulties in adult life.Life-course studies have shown that a small proportion of antisocial children are particularly badlyaffected in adulthood.Recent MRC funded work may help to identify such children early andcontribute to improved interventio

20、n and treatment.Dr Barbara Maughan from the MRC ChildPsychiatry Unit,London,together with UK and US colleagues,has used new statistical techniques toidentify children with different patterns of aggressive and non-aggressive antisocial behaviours inchildhood and adolescence.They found that high-risk

21、children fell into two distinct but overlappinggroups,which both had considerably disadvantaged family backgrounds and were highly vulnerable toother mental health problems in childhood.Journal of Quantitative Criminology 16,199-221Dr Dilys Morgan of the MRC Programme on AIDS in Uganda has led a res

22、earch team conductingdetailed clinical studies of HIV-1 infection and AIDS in rural Uganda for over 10 years.Her group hasfound that the average survival time and disease progression rate,are similar to those in industrialisedcountries before anti-HIV drugs were used.This research disproves the misc

23、onception that AIDS inAfrica is a distinct disease from AIDS in developed countries and that little can be done to prevent ortreat it.The work,which was part funded through the MRC/Department for InternationalDevelopment Concordat,also shows that there is a real opportunity to mitigate the effects o

24、f theAfrican AIDS epidemic.Nature Medicine 7,143-144A jointly funded MRC/World Health Organisation study by Professor Hilton Whittle and colleaguesat the MRC Laboratories in The Gambia,has surveyed 30,000 pregnant women to compare mother-to-child transmission rates of HIV-1 and HIV-2 viruses,which a

25、re both common in West Africa.Theyfound that women infected with HIV-1 had 37 times more virus in their blood than those with HIV-2 infection,and that this was reflected in the mother to child transmission rate,which was six timeshigher for HIV-1 infection.The findings firmly establish that HIV-1 re

26、plicates faster than HIV-2,explaining why HIV-1 infection spreads more easily and kills people more quickly.The knowledge willguide public health policies in The Gambia and other West African populations affected by both HIV-1 and HIV-2.AIDS 2000,14:411-448MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000

27、 20018Some scientists suggest that mens risk of HIV infection may be reduced by circumcision.ProfessorRichard Hayes group at the London School of Hygiene and Tropical Medicine,have analysed allavailable data on possible links between HIV-1 infection and circumcision in sub-Saharan African men.The po

28、oled results of seven such studies show that,taking everything into account,circumcised menare at about half the risk of HIV-1 infection as uncircumcised men.This protective effect was mostevident among men in high-risk groups,but was also seen in the general population.Current Opinion in Infectious

29、 Diseases 14,71-75Childhood obesity is an increasingly severe problem,but until now there has been no standard way tomeasure it;making it impossible to compare obesity rates from different studies.Professor Tim Colefrom the Institute of Child Health,working with colleagues from the International Obe

30、sity Task Force(IOTF),has devised a new definition of child obesity,which is based on the body-mass index(BMI weight(kg)/height(m)2)and applies world-wide.Children whose BMI is greater than the thresholdcalculated for their age are obese.Age thresholds are based on six large international surveys an

31、d arelinked to those for adult obesity.The IOTF definition should clarify the scale and growth of the childobesity epidemic internationally.British Medical Journal 320,1240-43The MRC General Practice Research Framework has studied asthmatic patients to address concernsthat long-term regular use of d

32、rugs like salbutamol,a bronchodilator which relieves asthma symptomsby widening the lungs airways,may mask an underlying deterioration in the condition.After one yearthey found similar asthma control in patients taking intermittent bronchodilators and those takingsalbutamol four times a day.The stud

33、y provides reassurance that regular use of salbutamol should notmake asthma worse,however,the need to use that much suggests that the ailment could be bettercontrolled,and indicates that additional treatment should be considered.Lancet 355,1675-79Young people in South Carolina,USA have unusually hig

34、h rates of end-stage kidney disease,largelydue to high blood pressure and diabetes.Researchers at the MRC Environmental Epidemiology Unitinvestigated whether poor kidney development before birth might account for this.They compared thebirth weights of 1230 people with kidney failure to 2460 controls

35、,and found that people who weighedless than 2.5 kilogrammes at birth were at increased risk of developing kidney failure.Since low birthweight is more common in South Carolina and the South East than in other areas of the USA,thiswork provides one explanation for the higher rates of chronic kidney f

36、ailure seen in this region.It alsoindicates that improving babies health could help reduce the predicted increase in long-term kidneydialysis patients over the next 40 years.Archives of Internal Medicine 160,1472-76Professor Julian Leff and colleagues from the Institute of Psychiatry,London,have com

37、pareddifferent approaches to treating depression,and shown that couple therapy,a psychological treatment,is more effective in improving depression than antidepressant drugs.Couple therapy aims to helpdepressed people and their partners gain new outlooks on the depressed persons problems,attach newan

38、d more positive meanings to the depressed persons behaviour and to experiment with new ways ofrelating to each other.Over the course of a year,the team treated some depressed people withantidepressant drugs,and others through couple therapy sessions with their partners.They followed-up the patients

39、for a further year after the treatment stopped.They found that couple therapy was themore effective treatment,both during and some time after the treatment period,and that fewer peopleMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 20019dropped out compared to the drug treatment group.The findings provi

40、de a strong argument fortraining primary care workers in the skills of couple therapy.British Journal of Psychiatry 177,95-100IMMUNITY AND INFECTIONMost cancer treatments are not very specific and attack normal cells as well as tumour cells.Dr.TerryRabbitts group,at the MRC Laboratory of Molecular B

41、iology,has designed molecules that selectivelykill cancer cells without harming normal ones.Their anti-cancer molecules have two parts,one thatrecognises and binds only to certain abnormal proteins specific to cancer cells,and another thattriggers the bodys own cell-death mechanisms to kill those ce

42、lls.This work could be translated intoclinical treatment for many common cancers.Proceedings of the National Academy of Sciences 97,12266-71Macrophages are large scavenger cells that help clear inflamed tissue and are involved in mediating thebodys immune response to infection.Professor Neil Barclay

43、 from Oxford and a team from theDNAX Research Institute,California,have shown that a molecule called CD200 is important ininhibiting macrophage activation.CD200 normally down-regulates macrophage cells in many tissuesby interacting with an inhibitory receptor molecule called CD200R.They found that m

44、ice lackingCD200 have more active,and more numerous,macrophages than normal,and are more susceptible tocertain auto-immune diseases,for example,a mouse-model of human Multiple Sclerosis(MS)in whichmacrophage over-activation results in nerve and tissue damage.These effects have important andbroad imp

45、lications for the treatment of neuro-degenerative diseases like MS and Alzheimers disease.Science 290,1768-71The pneumococcus bacterium is the main cause of pneumonia and an important cause of meningitisin children in the developing world.It currently kills about one million children every year,but

46、a newkind of vaccine called pneumococcal conjugate vaccine holds great promise for preventing thisinfection in the future.After many years of background epidemiological work and pilot vaccine trials,Professor Brian Greenwood from the London School of Hygiene and Tropical Medicine and hiscolleagues f

47、rom the MRC Laboratories in The Gambia have started a large clinical trial of such avaccine.The trial will last for 5-6 years and could lead to the introduction of a pneumococcal conjugatevaccine into the routine immunisation programme for children in developing countries.Lancet 356,1210-11Leukaemia

48、 and other blood disorders can be cured with transplants of stem cells,or stem-cellcontaining bone marrow,which replenish healthy blood cells.Unfortunately,such transplants arecontaminated with immune system cells called T cells,which attack the patient causing a serious illnesscalled graft-versus-h

49、ost disease.Professors Hale and Waldmann from the Therapeutic AntibodyCentre in Oxford have worked for many years to perfect a method for removing T cells withoutdamaging the stem cells;but have found that T cell removal makes patients more likely to reject thetransplant.They have now developed an a

50、ntibody which can be simply mixed with donor cells toprevent graft-versus-host disease and rejection.Many of the clinical trials were carried out in SouthAfrica where the treatment has so reduced the cost of stem cell transplantation that it is made availableto patients where otherwise it could not

51、be afforded.Bone Marrow Transplantation 26,69-79MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200110Immune responses to the Chlamydia bacterium are double edged;they help cure the infection butoften lead to tissue damage.In designing new vaccines or treatments it is important to distinguishbetween ben

52、eficial and damaging immune responses.Professor Gaston and colleagues fromCambridge have searched recently completed Chlamidia gene sequence data to find previouslyunknown Chamydia proteins that are recognised by the immune system.They plan to determinewhether immune responses to one of these protei

53、ns occur more frequently in patients with Chlamydia-induced tissue damage and inflammation.European Journal of Immunology 31,1513-1522The Brain Inflammation and Immunity Group at the University of Wales College of Medicine,headedby MRC Senior Fellow Dr Philippe Gasque,is working to characterise the

54、mechanisms involved inclearing disease causing organisms and toxic cell debris,such as dying cells,from the brain.Theybelieve that nerve cells themselves can distinguish intruders and induce cell debris removal,whilepreserving normal brain cells.This local scavenger system is essential to prevent br

55、ain infections,suchas meningitis,and ultimately to activate tissue repair following injury,for example,damage caused by astroke.They are studying the role of a receptor protein family involved in the uptake and destructionof harmful material.Journal of Biological Chemistry 275,34382-92Greater unders

56、tanding of how immune system cells are stimulated and regulated is necessary to helpdevelop efficient vaccines and disease treatments.Dr Rose Zamoyska and her group at the NationalInstitute for Medical Research have developed a model system to investigate the role of a protein calledlck,that it is i

57、nvolved in the proliferation and activation of immune system T cells.These studies willhelp to find out how these cells are regulated,and inform approaches to vaccine design and to tacklingunwanted immune responses,such as autoimmune diseases.Science 290,127Dendritic cells(DC)have been known to play

58、 a role in provoking and controlling immune responsesfor many years,but the molecular mechanisms involved remain obscure.Professor Herman Waldmannand colleagues from the Sir William Dunn School of Pathology,Oxford have begun to decipher thegenetic code that defines a DC by directing the process that

59、 generates DC from embryonic stem cellprecursors.This work provides a powerful new approach to identifying the function of individualgenes,and suggests new ways of intervening in autoimmune disease and transplant rejection throughtaming DC activity.Current Opinions in Immunology 12,528-35GENETICS,MO

60、LECULAR STRUCTURE AND DYNAMICSProfessor Steve Brown and colleagues from the MRC Mammalian Genetics Unit,in collaboration withSmithKline Beecham,have used powerful genetic approaches to generate a large resource of mousestrains,many of which carry new genetic mutations.A comprehensive screen of the n

61、ew strains,usinga series of tests,has identified over 500 potential mouse models for a diverse range of human diseasesincluding;osteoporosis,kidney failure,diabetes,abnormal cholesterol processing,spina-bifida,sightand hearing impairments.These models will help to identify gene defects causing human

62、 disease andfurther our understanding of how and why disease develops.Nature Genetics 25,440-43MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200111Professor Robert Plomin from the Institute of Psychiatry has built on a surprising finding from humangenetic research that the same genes affect many diffe

63、rent cognitive processes,to develop a geneticmouse model of human learning and memory processes.The mice will be invaluable for identifyingand understanding genes involved in cognitive disorders.Nature Reviews Neuroscience 2,136-41The recent production of a first draft of the human genome is freely

64、available on the internet.Dr ChrisPonting from the MRC Functional Genetics Unit in Oxford contributed to this collaboration byinvestigating how the set of human genes differs from those of worms,flies,plants and fungi.It isclear that although these organisms proteins are all assembled from a similar

65、 repertoire of ancientgene segments,human proteins are assembled in a much more complicated way.Nature 409,860-921A team of international scientists,led by Professor Mike Owen from the University of Wales Collegeof Medicine,has discovered new evidence of a gene involved in the common form of Alzheim

66、ersdisease.Their study of 429 Welsh and American sibling pairs over the age of 65 with Alzheimersfound that around two thirds of pairs shared the same genetic characteristic on chromosome 10,revealing that there is at least one major gene for the disease nearby.Identifying the responsible gene,or ge

67、nes,could in the longer term lead to new and better treatments for Alzheimers.Science 290,2304-05Very large numbers of patients must be tested to find genes contributing to common diseases such asasthma.Professor Newton Morton and Dr Andrew Collins from Southampton University have set upan internati

68、onal consortium of 10 groups looking for asthma genes and have developed ways tocombine the data that each group contributes to show where these genes might be.An initial analysisof chromosome 5 in a combined sample of 1037 families showed that a particular region may containasthma genes.Chromosome

69、12 is the next target for analysis.Eventually,the consortium plans toreview all asthma gene candidate regions,and to extend the analysis using techniques that enable themto home-in on asthma genes.Proceedings of the National Academy of Sciences 97,10942-47TolC is a bacterial membrane protein that is

70、 central to disease causing capability and multidrugresistance in many infecting microbes.MRC programme grant holders Dr Vassilis Koronakis and DrColin Hughes from Cambridge University have made and analysed TolC crystals,to reveal aremarkable and as yet unique molecular structure,which they call th

71、e“channel tunnel”.This providesa large exit duct for a wide range of molecules,from large bacterial toxins to small antibacterial drugs.This is the culmination of many years work and has unveiled a previously unsuspected strategy usedby infectious bacteria,which may provide a target for new drugs.Na

72、ture 405,914-19DNA damage arises constantly from both normal cellular processes and environmental hazards suchas radiation and chemicals.Accurate DNA repair is vital to survival,and all living organisms,includingman,have specific mechanisms to do this.Professor John Thakkers group at the MRC Radiati

73、on andGenome Stability Unit has recently isolated a gene called Xrcc2 and found that it belongs to a genefamily which repairs broken DNA molecules.They created mice lacking the gene to assess its role ingenetic stability and cancer,and found that Xrcc2-deficient mouse embryos show an increased level

74、 ofMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 20011212chromosome defects compared to normal mouse embryos,have developmental abnormalities,and donot survive beyond birth.Surprisingly the embryos also have neurological defects,with certainparticularly sensitive neurons in the developing brain dying

75、prematurely.The researchers suggest thatunrepaired DNA damage that persists in certain brain cells triggers cell-death,leading to poorneurological development and embryonic death.EMBO Journal 19,6674-85Fibrillin molecules provide long-range elasticity to connective tissues through outer cell-surface

76、assemblies that form extensive linear microfibrils and act as a template for elastin fibre formation.Mutations in fibrilin-1 cause the arterial weakness,and skeletal and eye defects of Marfans Syndrome.MRC Senior Fellow Professor Cay Kielty and colleagues from Manchester,have used state of the artel

77、ectron microscopy to determine the 3D structure of fibrillin microfibril assemblies and haveproposed a new model for their alignment.Additional work has established how cells synthesise andsecrete fibrillin molecules and regulate their cell-surface assembly.Science Now 24 October 2000The primary hum

78、an defence mechanism against microbial infection relies on cells that ingest invadingmicro-organisms and then kill them with highly reactive oxygen derivatives.The source of theprotective oxygen-based cell-killing molecules is a large membrane-associated multi-protein complexcalled NADPH oxidase.How

79、ever,inappropriate NADPH oxidase activation can also lead toinflammation and tissue damage.Dr Katrin Rittinger and colleagues at the National Institute forMedical Research have determined the structural details of the interaction between two NADPHoxidase components.Their work will help to reveal how

80、 the NADPH oxidase assembly is regulatedand might provide the basis for the design of new anti-inflammatory drugs.Molecular Cell 6,899-907Ribosomes are large molecular machines that cells use to make proteins.Ribosomes catalyse proteinchain synthesis by binding and translating the genetic code of me

81、ssenger RNA.A large number ofnatural antibiotics,including erythromycin,tetracycline,streptomycin and gentamycin work by bindingto ribosomes and disrupting protein synthesis.Dr Ramakrishnan and colleagues from the MRCLaboratory of Molecular Biology,have solved the molecular structure of one of the t

82、wo ribosomesubunits,both alone and bound to antibiotics.This work makes important contributions tounderstanding how proteins are made and how many antibiotics work.The results could be used tohelp design new antibiotics.Science 291,498-501The cone-shaped core of the human immunodeficiency virus(HIV)

83、is built from about 1500 subunitsof a protein called CA.Dr John Finch and colleagues from the MRC Laboratory of Molecular Biology,together with researchers from the University of Utah,have used a technique called cryo-electronmicroscopy to study tubular aggregates of CA protein.Computer analysis of

84、the resulting imagesshows that the CA protein has a symmetrical hexagonal arrangement.The same CA arrangement onthe surface of the conical viral particle gives the HIV core its particular shape.Nature 407,409-13MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200113CELL BIOLOGY,DEVELOPMENT AND GROWTHProf

85、essors Kondo and Raff from the MRC Laboratory of Molecular Cell Biology,have provided thefirst evidence that specialised precursor cells,destined to become a particular cell type,can bereprogrammed into stem cells,which are able to self-renew and generate a diverse range of other cells.If this prove

86、s to be true for other types of precursors,it could have implications for developing stemcell therapies,because precursor cells are easier to purify and expand than stem cells.Science 289,1754-57The human body resists invasion by disease causing bacteria,for example tuberculosis,by attackingthem wit

87、h highly reactive free-radical molecules inside immune system macrophage cells.In turn,bacteria have developed powerful,but as yet poorly understood,systems to protect themselves withinmacrophages.Studies of the stress signalling mechanism in fission yeast by Dr Jonathan Millar fromthe MRC National

88、Institute for Medical Research have uncovered an ancient mechanism that enablesmicrobes to sense hydrogen peroxide radicals.These sensors appear to be conserved in disease-causingbacteria,but not in humans,and may represent a target for new drugs that compromise the intracellularbacterial protection

89、 mechanism without affecting the host.Molecular Biology of the Cell 12,407-19Uncontrolled cell proliferation is a hallmark of cancer and certain other diseases.A family of enzymescalled the cyclin-dependent kinases(CDKs)control the progress of cell division,and regulation ofCDK activity is often los

90、t in cancer cells.Professor David Newell and colleagues from the Universityof Newcastle,working with AstraZeneca,are developing potent and specific inhibitors of CDKs tostudy the role of these enzymes in more detail,with a view to generating new drugs for cancertreatment.In the first year of their L

91、INK grant they have identified inhibitors as potent as the bestcompounds described in the literature so far.Journal of Medicinal Chemistry 43,2797-804Nutrients,including amino acids,are known to regulate cellular processes involved in protein synthesis,but the mechanisms that enable amino acids to e

92、xert these effects within cells are poorly understood.Experiments in which Professor Proud and colleagues from Dundee microinjected amino acidsdirectly into single cells have identified a putative intracellular amino acid sensor that is a keyintermediary in protein synthesis control.It is important

93、to identify and characterise this and othercomponents in order to dissect the ways cells respond to changes in nutritional status,for example,through starvation or as a result of diseases such as diabetes.Biochemical Journal 351,677-682Blood cells derive from stem cell precursors stored in the bone

94、marrow.A better understanding ofstem cell biology will make the treatment of blood diseases much easier.Stem cell activity is firstdetected during embryonic development at a site distinct from the yolk sac where embryonic blood isbeing made.However,there has been considerable debate about whether th

95、e stem cells originate insitu,or have migrated from the yolk sac.Work in the African toad Xenopus by Professor Roger Patientfrom Nottingham has shown that the site where the first stem cells are generated comes from a regionof the early embryo that is distinct from those which give rise to embryonic

96、 blood.His observationsindicate that different embryonic signals and nuclear factors programme stem cells and embryonicMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200114blood cells.Defining these signals and factors may make it possible to manipulate stem cells isolatedfrom adult bone marrow or from

97、 umbilical-cord blood.Cell 102,787-96Heparan sulphates are complex cell-surface molecules involved in binding and regulating the activitiesof many signalling proteins.Dr Jeremy Turnbull,MRC Senior Fellow at Birmingham,has collaboratedwith Dr Ram Sasisekharan from MIT to apply a mass spectroscopy-bas

98、ed technique to accuratelydetermine heparan sulphate structures.The method provides a tool for detailed analysis of therelationship between the structure and function of heparan sulphates,with the goal of identifying newtherapeutic targets.Proceedings of the National Academy of Sciences 97,10359-64G

99、lucocorticioids are a family of hormones,including cortisone and hydrocortisone,that are widelyused to suppress the inflammation which characterises conditions such as arthritis,asthma andtransplant rejection.They inhibit the production of cell-to-cell signalling molecules called cytokines,and enzym

100、es that drive inflammation.Genes expressing these inflammatory molecules are activated inresponse to cell-surface signals,such as the recognition of microbial products,that are transduced tothe cells nucleus by pathways of proteins called kinases.Professor Saklatvalas group at the KennedyInstitute,I

101、mperial College,has shown that the glucocorticoid,dexamethasone,inhibits activation of akey component of these pathways,called p38MAP kinase.Their work suggests that dexamethasoneinduces an anti-inflammatory regulator,whose identification should give new insights into the controlof inflammation.Mole

102、cular Cell Biology 21,771-80Professor John Gordons group at the MRC Centre for Immune Regulation at Birmingham is exploringnew ways to kill lymphoma tumour cells.Lymphoma is often incurable because these cancer cells areloaded with survival genes.The researchers have found that minute amounts of a n

103、aturally producedtoxin from the food poisoning bug E.coli O157 are able to kill cultured lymphoma cells,even whenhigh levels of the survival genes are present.The work gives insight into ways of using the toxin totreat patients in the future.Cell Death and Differentiation 7,785-94Professor Mark Mars

104、h and colleagues at the MRC Laboratory for Molecular Cell Biology,London,incollaboration with Professor James Hoxie at the University of Philadelphia,are working on the simianimmunodeficiency virus(SIV),the monkey equivalent of HIV.They have identified molecular signalsthat regulate SIV coat protein

105、 distribution in SIV infected cells and,together with Professor Fultz ofthe University of Alabama,have now shown that removing one of these signals significantly decreasesthe ability of SIV to cause disease.The research illuminates previously unknown viral mechanisms thatmay also apply to HIV and of

106、fer the potential for new therapies.Journal of Virology 75,27-91A vital brain function is to“bind”together the visual features that make up complete objects,forexample,a nib,a barrel and a cap,form a pen.Professor Mark Johnson and colleagues from the Centrefor Brain and Cognitive Development,London,

107、have used non-invasive brain-imaging to show thatthis ability develops during the first year of life.They saw characteristic high frequency electricalMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200115oscillations associated with binding in adult brains in healthy eight month old babies,but not in si

108、xmonth olds.This work provides one of the first glimpses of how the pre-verbal infants brain works.Science 290,1582-85Dr David Jane and colleagues from the MRC Centre for Synaptic Plasticity at Bristol University,haveadvanced understanding of glutamate receptor proteins,which mediate cell-to-cell si

109、gnalling in thehuman brain.They have designed a compound which specifically activates a subytpe of glutamatereceptors called mGlu8 and shown that these play an important role in regulating communicationbetween nerve cells in the spinal cord.Further work on this compound,together with Professor Brian

110、Meldrum from the Institute of Psychiatry,has shown that it has anticonvulsant properties and thatsuch compounds might therefore provide new epilepsy treatments.Neuropharmacology 40,311-18MEDICAL PHYSIOLOGY AND DISEASE PROCESSESParathyroid hormone(PTH)controls the balance of calcium and phosphate in

111、the body.John Pottsfrom the Harvard Medical School,Boston,USA,characterised the structure of the active part of PTHand made pure PTH available in an MRC-Harvard collaboration.Although early reports that PTHincreased bone density in young animals were widely disregarded,Dr Jonathan Reeve and colleagu

112、esfrom Cambridge decided to test PTHs effectiveness in patients with severe osteoporosis,which waspreviously untreatable.They found that PTH increased bone formation much more than bonereabsorption,which was the opposite to what other people had expected,and that osteoporosis wasoften abolished.This

113、 was a much greater effect than that achieved with rival modern treatments.Journal of Bone and Mineral Metabolism 19,102-114Macrophages are cells that engulf microbes and other invading materials and facilitate immunereactions against them.In certain immune diseases such as rheumatoid arthritis,ther

114、e is an abnormalaccumulation of macrophages in the inflamed joint,where these cells may have damaging effects.Professor Ten Feizi and colleagues from Imperial College have advanced understanding of a proteincalled the macrophage receptor which is important in the protective function of macrophages.P

115、rofessor Feizis group has discovered that the macrophage receptor can bind to components of jointcartilage.This work could aid our understanding of prolonged joint inflammation and inform thedevelopment of new anti-inflammatory treatments for arthritis.Journal of Experimental Medicine 191,1117-26Ost

116、eoarthritis is traditionally seen as a disease of the smooth,gristle-like cartilage that lines thesurfaces of joints.MRC Senior Fellow Professor Richard Aspden and his group from the Universityof Aberdeen have already shown that significant changes also occur in the bone,even at some distancefrom jo

117、int surfaces,and that these changes cannot be explained as secondary consequences of cartilagedisease.They are now looking for mechanisms that can explain why several joints are often involvedand why there is such a strong link with obesity.They propose that generalised osteoarthritis is asystemic d

118、isorder related to lipid metabolism.This idea links metabolic factors with mechanisms thatcan regulate the whole skeleton,and suggests new explanations for joint degeneration.Lancet,357 1118-112016MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 2001To apply gene therapy to nervous system diseases it is

119、necessary to be able to deliver genes to nerve cells,however the inaccessibility and specialised nature of these cells makes this a difficult challenge.Professor Charles Coutelle and colleagues from Imperial College,have developed a gene delivery systembased on part of the tetanus bacterium toxin,ca

120、lled the He-fragment,which is non-toxic and is able tobind to and enter nerve cells.Although the He-fragment system was only effective in cultured cells,theteam has achieved selective gene delivery to the brain stem by using the He-fragment to re-target a gene-bearing virus,which had been injected i

121、nto muscle,to nerve cells.In the longer term this research maylead to the development of gene delivery systems that can be used to treat neurological diseases.Gene Therapy 7,1584-92Structures known as plaques,which contain fats and the protein collagen,accumulate in our arteries aswe age.Collagen is

122、 normally found in blood vessel walls,and only comes into contact with blood whenthe vessel is injured,at which time small blood cells called platelets stick to the collagen and clump toplug the leak.If a plaque splits,exposed collagen can cause a clump that blocks the vessel and leads toa heart att

123、ack.Professor Farndale and colleagues from Cambridge have analysed crystallised plateletand collagen proteins to understand the binding process at the atomic level.Their results will informthe design of new drugs to stop this process.Cell 101,47-56Determination of the bodys cell types depends on whi

124、ch genes are expressed and how geneexpression patterns are maintained during cell division.Altered gene expression underpin cancer andmany other disorders.Dr Niall Dillon and colleagues from the MRC Clinical Sciences Centre,havemade a major contribution to our understanding of how specific intracell

125、ular proteins,calledtranscription factors,regulate gene expression by altering chromosome structure.The work hasimplications for achieving appropriate gene expression following gene therapy and also foraccomplishing successful therapeutic cloning.Cell 103,733-443Magnetic Resonance Imaging(MRI)is a p

126、owerful tool for examining the bodys internal organs formedical diagnosis and research.A team at the MRC Clinical Sciences Centre,working with Marconi,has developed a new material,known as microstructured magnetic material,that may lead to dramaticimprovements in the performance of MRI systems.Micro

127、structured magnetic material helps to obtainimages by guiding radio-frequency magnetic flux from the body to the receiver coils of an MRIscanner.To demonstrate its potential,the team placed the material between the object a researchersthumb and a small receiver.They obtained a clear image of the thu

128、mbs internal structure.In controlexperiments where the material was replaced by a piece of inert plastic the thumb was not detected.Science 291,849-51MRC Professor Ole Petersen and colleagues at the University of Liverpool have shown that changesin the pattern of calcium release within cells,leads t

129、o changes similar to those seen in patients withacute pancreatitis.An abnormal prolonged rise in the calcium concentration inside the pancreatic cellstriggers an activation of digestive enzymes that start to digest the pancreas itself,rather than digestingfood in the gut,often with fatal results.The

130、 inappropriate enzyme activation does not occur whencalcium is prevented from entering the pancreatic cells.Drugs aimed specifically at blocking theexcessive calcium entry could therefore be used to treat pancreatitis in the future.Proceedings of the National Academy of Sciences 97,13126-13131MEDICA

131、L RESEARCH COUNCIL ANNUAL REPORT 2000 200117Professor Lowry and his team from the University of Reading have made a breakthrough in theunderstanding of pre-eclampsia,which is a major,and potentially fatal,cause of fetal and maternalillness.It affects one in ten pregnancies world-wide.Currently the o

132、nly treatment is to deliver the babyprematurely by caesarean section,which means that the baby often requires further intensive care.Theteam has discovered that a small protein called neurokinin B(NKB),which is secreted by the placenta,is raised significantly in mothers when pre-eclampsia develops.N

133、KB can be detected as early as week9 of pregnancy making it a potentially useful pre-eclampsia screening tool.Clinical studies are nowbeing initiated to test whether a drug called neurokinin receptor antagonist,which is already available,could block the action of NKB and thereby alleviate this dange

134、rous condition.Nature 405,797-800Asthma is a disorder of the airways whose incidence world-wide is increasing due to factors linked toa Western life-style.Its symptoms of wheeze,shortness of breath and cough,result from acombination of inflammation and changes in airway structure known as remodellin

135、g.MRC ProfessorStephen Holgate and his group from Southampton University have studied the disease in humanvolunteers to show that the airway-lining epithelial cells that form a barrier to the external environmentare more susceptible to injury in asthma sufferers.Epithelial damage activates the under

136、lying structuralcells to promote remodelling and increased inflammation leading to excessive responsiveness,loss oflung function and reduced responses to treatment.This underlying epithelial sensitivity may explainwhy environmental and dietary changes have led to the rising trends in asthma.FASEB Jo

137、urnal 14,1362-74NEUROSCIENCE AND MENTAL HEALTHIn order to identify new drug targets,Professor John Wood and colleagues from University CollegeLondon have generated mice lacking the gene for a protein involved in electrical signalling in damage-sensing nerves.These mice have higher pain thresholds,bu

138、t are otherwise completely normal.Thissuggests that a drug acting on the channel would be a good pain-killer,free from side effects.Current Opinions in Pharmacology 1,17-21A disease called Dementia with Lewy bodies(DLB)is one of the major causes of dementia in old age.Changes seen in patients brains

139、 suggest that they might be particularly responsive to new Alzheimersdisease drugs called cholinesterase inhibitors.Professor Perry and colleagues from theMRC/University Centre Development in Clinical Brain Ageing at Newcastle,with industrial supportfrom Novartis,have conducted the first multicentre

140、,placebo-controlled trial of the cholinesteraseinhibitor rivastigmine.The drug produced significant improvements in the core clinical features of thedisease,reducing hallucinations,delusions and agitation.This finding is leading to further trial studiesand is already changing clinical practice as DL

141、B patients are starting to receive the treatment.Lancet 356,2031-36Most organisms possess a biological clock with a daily rhythm of about 24h,known as a circadianclock,which helps them to synchronise their activities to daily changes in the environment.ProfessorTony Harmars team at Edinburgh Univers

142、ity has discovered that a chemical messenger,vasoactiveintestinal peptide,is an important regulator of the brains circadian clock.This discovery may lead tothe development of drugs that can be used to alleviate the impaired physical and mental well-being thatcan occur through shift work,jet lag,deme

143、ntia,and in normal ageing.Proceedings of the National Academy of Sciences 97,11575-580MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 2001Professor Richard Morris and colleagues from Edinburgh University working with ElanPharmaceuticals of Dublin and San Francisco,have advanced understanding of Alzheime

144、rs diseasethrough the development of a new diagnostic memory test for a mouse Alzheimers model.The lossof recent memory that characterises Alzheimers may or may not be related to the formation ofextracellular nerve-cell debris deposits,called beta-amyloid plaques.The new test has been examinedin tra

145、nsgenic mice that over express human mutant beta-amyloid and deposit plaques.As they getolder,the mice lose their ability to remember recent information in proportion to plaque deposition.Versions of the test have already proved useful for examining a new anti-Alzheimers vaccine.Nature 408,975-79The

146、 habitual behaviour of many opiate addicts means that they often experience the adverse effects ofdrug withdrawal in specific environments.Subsequent exposure to the same conditions can be enoughto trigger a conditioned withdrawal response that often involves drug craving,drug seeking and relapseto

147、addiction,even in people who have not used drugs for a long time.Professor Barry Everitt andcolleagues from Cambridge,demonstrated that this phenomenon depends on part of the brain calledthe basolateral amygdala,since damage to this structure completely prevented conditioned withdrawal.This finding

148、suggests that new drugs that are able to modify the changes in the amygdala which occurduring re-exposure to environmental cues might disrupt the reaction they prompt and so help to treatopiate addiction.Nature 405 1013-1014It is well known that“intelligence tests”are useful in practice,but there ha

149、s been a century-long debateabout what these tests measure and why they are adept at predicting success in many important activities.Dr John Duncan and colleagues from the MRC Cognition and Brain Sciences Unit,with collaboratorsfrom Germany,used a technique called positron emission tomography(PET)to

150、 investigate what aspectsof human brain activity intelligence tests actually measure.Their results show that particular frontal loberegions are selectively employed during intelligence tests,suggesting that general intelligence reflects thefunction of a specific frontal lobe system important in orga

151、nising diverse activities.Science 289,457-60Although the origin of most forms of epilepsy is unknown,a genetic cause is suspected in many cases.MRC Senior Fellow Dimitri Kullman and colleagues from the Institute of Neurology,working as partof an MRC Co-operative Group,have examined families that car

152、ry mutations of a potassium channelgene.This has previously been associated with a rare disease called episodic ataxia type 1,that affectsbalance and movements.The team reported for the first time that episodic ataxia type 1 patients areaffected in different ways,and that some have epilepsy as part

153、of the disease.Test-tube studies ofpotassium channel function showed that mutations associated with a severe form of the disease causegreater disruption than those associated with a mild form.This provides a mechanistic link betweenthe mutation and the disease,and sheds light on channel function.Ann

154、als of Neurology 48,647-56Glial cells form the specialised supporting tissue that surrounds nerve cells.In the brain,a type of glial cellcalled oligodendrons provide insulating sheets for the branches of nerve cells,enabling them to conductsignals at high speed.Oligodendron damage results in the wid

155、espread neurological disorder multiple sclerosis.Glial cells were previously thought to communicate with each other and with nerve cells through muchslower signals than used by nerve cells.Now,Professor Peter Somogyis group at the MRC AnatomicalNeuropharmacology Unit,with collaborators from the USA,

156、have discovered that cells called18MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 2001oligodendrocyte precursor cells(OPCs),which generate new oligodendroglial cells,receive fast signals fromnerve cells through synapses which use the same signalling molecules as used between nerve cells.Forexample,they

157、 found that OPCs in a brain area involved in learning and memory,receive signals mediated bythe neurotransmitter glutamate.The discovery of fast signalling from nerve cells to OPCs opens up newavenues for regulating their function,which could lead to the treatment of multiple sclerosis.Nature 405,18

158、7-91Our understanding of how general anaesthetics work has advanced greatly over the last few years.Recently,Professor Nick Franks and his colleagues at Imperial College,working as part of an MRC Co-operativeGroup in General Anaesthesia and Neuronal Excitability,have identified the likely target for

159、 xenon gas,whose anaesthetic and pain relieving properties have been known for over 50 years.Their work suggests thatxenon acts on a protein called the NMDA receptor,which is a widespread neurotransmitter receptor that isbelieved to play an important role in memory,learning and the perception of pai

160、n.The possible clinical usesof xenon will be a future focus for the team.Anaesthesiology 92,1055-66Stroke occurs when a large blood vessel in the brain becomes blocked,causing prolonged biochemicalchanges that result in nerve cell death in the brain tissue which the vessel supplied.A study by Dr Jon

161、athanMarshall and colleagues from the MRC Comparative Cognition Team in Cambridge,in collaboration withAstraZeneca,has demonstrated that a drug designed to minimise these biochemical changes,provides veryeffective brain tissue protection when given to a primate species following experimentally induc

162、ed stroke.There are long-term benefits in skilled arm and hand use and more rapid recovery from spatial neglect,adebilitating mental stroke symptom in which the brain ignores events occurring in the side of space oppositethe damaged area.The drug may therefore have valuable applications in a wide ra

163、nge of brain damage,including head injury and birth complications,and reduce long term disability following stroke.This wouldprovide substantial cost savings to Health and Social Services.Stroke 32,190-98A team of researchers led by Professor John Collinge at the MRC Prion Unit has found new evidenc

164、e forthe existence of a symptomless,“sub-clinical”,form of the prion disease BSE in mice.They tried to infectmice with hamster prions and although the mice showed no apparent signs of disease,closer examinationrevealed that they had high levels of mouse prions in their brains.The result was surprisi

165、ng since it had alwaysbeen assumed that hamster prions could not cause the disease in mice,even when injected directly into thebrain.The team also found that this previously unknown sub-clinical infection could be easily passed onwhen injected into healthy mice and hamsters.Their findings suggest th

166、at just because one species appearsresistant to a strain of prions they have been exposed to,it should not be assumed that they are not silentlycarrying the infection.The data also lend weight to the view that apparently healthy cattle could harbour butnever show signs of BSE.Proceedings of the Nati

167、onal Academy of Sciences 97,10248-5319MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200121380m by 2003.53m of this extra money hasbeen earmarked for Genomics research,with anadditional 12m capital funding for relatedinfrastructure.8m is reserved for E-Science(bioinformatics,health informatics and grid

168、testbeds,part to be committed jointly withBBSRC)and the remainder will contribute toProgress is continuing in the two priority areas for MRC funded under the 1998 ComprehensiveSpending Review(CSR).These are the Post Genome Challenge and Health of the Public.Recentdevelopments include:POST GENOME CHA

169、LLENGEdistribution of human and mouse gene arrays to the additional funding awarded following large scale calls for academic community free-of-charge(p23)proposalscollection of DNA samples from large disease focussed increased funding provided for primary care research(p27)cohorts in order to establ

170、ish the resources required to study the genetic basis of complex disease(p30)call for expressions of interest as the first stage inadditional funding awarded with ESRC under the Innovative establishing a UK network for DNA sample banking and Health Technologies programme genotyping(p31)MAD beamline

171、at ESF funded jointly with BBSRC and Funders Fora established in cancer,ageing and EPSRC for UK crystallographers(p26)cardiovascular disease(p.29,30)Discipline Hopping Awards launched to promote the Review commissioned by the DH on the incidence,causes application of chemistry and physics in the lif

172、e sciences(p21)and biomedical treatments for autism(p27)workshop to examine the key priorities for future research resolution of the future location of the General Practice in bioinformatics and to inform the community about Research Framework Centre to the MRC Clinical TrialsUnit developing computi

173、ng infrastructure in the UK,known at University College,London(p27)as“the Grid”(p26)COMPREHENSIVE SPENDING REVIEWRESEARCHother research developments2HEALTH OF THE PUBLICSPENDING REVIEW2000The spending review to determine the levels ofscience funding for 2001/02 to 2003/04(SR2000)began in the Autumn

174、of 1999 and theallocations were announced by the Governmentin November 2000.MRCs income has beenboosted by 89m above the level established bythe CSR.This increases the annual budget toMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200122Within the University sector,the MRCcontinues to provide support f

175、or a variedresearch portfolio through a range of grantschemes.Details of all grant schemes and ofcurrent awards are on the web site.In 2000MRC made awards totalling 155m for researchin universities and teaching hospitals.CENTRE GRANTSMRC Centre Grants aim to supportmultidisciplinary research-centred

176、 environments inpartnership with universities.They involvesignificant investments by both the MRC and thehost universities with full-time scientific leadership.MRC awarded two Centre Development Grants in2000/01,on the important topics of Clinical BrainAgeing(Newcastle)and Genome Damage andStability

177、(Sussex).The Sussex Development islooking at the processes which can cause some cellsin the body to become cancerous.The Edinburgh Centre for InflammationResearch was formally opened in February 2001by Sir George Radda and Professor Sir StewartSutherland,Principal of Edinburgh University.CO-OPERATIV

178、E GROUP GRANTSThese awards draw together researchers toimprove the overall output of research andenhance individual research projects(supportedby Component Grants where funded by MRC).In 2000 the MRC set up 39 new Co-operativeGroup Grants throughout the UK.Over a thirdof Co-operative Groups involved

179、 interests ofother Research Councils.These new Co-operative Grants support the research projectsof over 200 scientists funded through MRCComponent Grants and by a wide range ofother funders.New Co-operative Groupsinclude a grant to Dundee University inpartnership with the Cancer Research Campaigninv

180、estigating the most commonly mutated genein human cancer.Another Co-operative Grouphas been established in Oxford to improve ourknowledge of the physiology of the heart so thatnew therapies for heart disease can bedeveloped.This Co-operative is also supportedby grants from the British Heart Foundati

181、on.Important awards in the field of mental healthinclude groups at the Institute of Psychiatryexploring the developmental basis ofschizophrenia,whilst groups at Imperial Collegeand the Royal Free Hospital are developingimproved interventions for mental health problems.Many of the Co-operative Group

182、Grants arelinking basic and clinical research(e.g.epilepsy),enabling scientists to use multidisciplinaryapproaches on major scientific problems ofimportance to human health.Core support isproving particularly valuable for the appointment ofkey scientific co-ordinator posts,which would bedifficult to

183、 fund through other mechanisms.CAREER ESTABLISHMENT GRANTSCareer Establishment Grants are awarded forfive years to recently appointed clinical and non-clinical university scientists.The scheme aims tofacilitate their establishment as independentinvestigators capable of winning further supportin open

184、 competition.Council was able to make27 awards in 2000(1.43m),the third year ofoperation.Eight of the Career EstablishmentGrants awarded involved clinical research.SUPPORTING RESEARCH EXCELLENCE IN UNIVERSITIESother areas including stipend increases forgraduate students.A further 41m wasallocated fo

185、r Basic Technologies;this is beingmanaged by EPSRC on behalf of all theResearch Councils and will be allocated via opencalls for proposals in important new areas.Mechanisms for ensuring co-ordinationbetween the Research Councils have been put inplace for each of the three highlighted areas.MEDICAL R

186、ESEARCH COUNCIL ANNUAL REPORT 2000 200123INNOVATION GRANTSThese grants provide small-scale,short termfunding for high risk,speculative or innovativeresearch.Awards are made on the basis of theapplicants track record of achievement fromprevious MRC funding.12 new awards(0.57m)were made from the appli

187、cationsconsidered in 2000.DISCIPLINE HOPPING AWARDSMRC launched Discipline Hopping Awardsduring the year to encourage researchers alreadyestablished in the physical sciences to spend timeapplying their expertise to problems in the lifesciences.The awards,of up to 50,000 for a oneyear period,are aime

188、d at pump priming newinterdisciplinary collaborations.EPSRC providedsupplementary funding to the programme therebyenabling 24 projects to be supported acrossphysics,chemistry and engineering.OtherResearch Councils have recently expressed interestin the scheme;PPARC for example,contributedto one awar

189、d in the area of detector development.OTHER SCHEMES33 awards were made under the Joint ResearchEquipment Initiative(JREI)in 1999/00 totalling2.1m.In addition,thirty two awards weremade under the Realising Our Potential Awards(ROPA)scheme amounting to 3.1m.1.6mwas awarded via LINK awards.THE JOINT IN

190、FRASTRUCTURE FUNDThe fourth round of the Joint(OST,HEFCE,Wellcome Trust)Infrastructure Fund(JIF)tookplace in 2000.A total of 28 projects in 16universities have been funded,many in thebiomedical field.Awards which complementmajor MRC investments include grants toProfessor R Weiss(University College,L

191、ondon)on post genomic virology to advance researchinto ways of combating HIV.Funds have beenprovided for two 900MHz Nuclear MagneticResonance(NMR)facilities for the UKbiomolecular NMR community.SCIENCE RESEARCH INVESTMENT FUNDFor the future,JIF will be replaced by a newscheme the Science Research In

192、vestment Fund(SRIF).A total of 1bn has been madeavailable for SRIF,including 225m from theWellcome Trust.The Research Councils haveeach issued statements setting out their currentstrategic objectives so that the universities maytake these into account when preparingapplications to SRIF.INTER BOARD I

193、NITIATIVE GROUPIn September 2000,Council established an InterBoard Initiatives Group(IBIG).It will takeresponsibility for peer reviewing researchproposals that span the interests of more thanone MRC Board,or that are collaborative withother funding agencies and may require fasttrack decisions.IBIG m

194、eets four times a yearand its funding recommendations are assessedby Council in competition with all otherapplications.It is chaired by the Chief Executiveand the membership comprises the four BoardChairmen and Deputy Chairmen.Additionalmembers are co-opted to give specialist advice.CLINICAL RESEARC

195、HA series of visits to University medical schoolstook place during 2000 to help improve theamount and quality of research proposalssubmitted to MRC.Council discussed issuesarising from the visits.The next step is to look atthe potential value of Career EstablishmentGrants in establishing clinical re

196、searchers,Co-operative Group Grants in developing basicresearch that can lead to clinical application,andthe possible role of MRC units in supportinggood clinical research.MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200124MRC RESEARCH UNITS AND INSTITUTESNew AppointmentsMRC MOLECULAR HAEMATOLOGYUNIT

197、Professor Doug Higgs became theDirector of the Unit in October 2000,followingthe retirement ofProfessor Sir DavidWeatherall.Professor Higgs has worked in theUnit since its establishment 20 years ago and isone of the leading figures researching thegenetic basis for haematological diseases,and inparti

198、cular thalassaemia.New UnitsMRC CELL BIOLOGY UNIT Following areview of the MRC Interdisciplinary ResearchCentre in Cell Biology(University College,London),Professor Alan Hall was appointed on1 January 2001 to succeed Professor ColinHopkins as Director of the MRC Laboratory ofMolecular Cell Biology(L

199、MCB).He will prepareproposals for a new MRC Cell Biology Unit toform the core of the LMCB.Other Unit DevelopmentsMRC CANCER CELL UNIT The newbuilding for this Unit,which has been jointly fundedby the MRC and Cambridge University,is nowcomplete and is in the process of being fitted out.It is anticipa

200、ted that the Unit,to be directed byProfessor Ron Laskey,will open formally in theSummer of 2001.MRC TOXICOLOGY UNITProfessorPierluigi Nicotera took up his appointment asDirector of the Unit on 1 October 2000.It isintended that the Units focus will be redirectedtowards understanding the molecular and

201、cellular mechanisms that regulate celldysfunction and cell deathMRC RESOURCE CENTRE FORHUMAN NUTRITION RESEARCH TheResource Centre,which is directed by Dr AnnPrentice,moved into new purpose built facilities-the Elsie Widdowson Laboratory Cambridge-on 1 January 2000.The Laboratory providesstate of th

202、e art facilities for human volunteerstudies,genetic,biochemical and metabolicresearch aimed at providing scientific evidenceof the relationship between nutrition and healthto underpin public health policy.MRC HUMAN MOVEMENT ANDBALANCE UNITIn October 2000,weconsidered the future of this Unit followin

203、g thedeath of its previous Director.It has beendecided that the Unit should close on 31March2001.However,in recognition of the importanceof the field and quality of the Units research,Council agreed that the science should continueto be funded via programme grant support.MRC HUMAN IMMUNOLOGY UNITThe

204、 Phase I trial of a novel DNA/MVA vaccineagainst HIV began in Oxford in August 2000.This is the culmination of many years ofresearch led by Professor Andrew McMichael,the Unit Director.The Oxford trial isproceeding well and a complementary Phase INairobi trial has recently begun recruitment.Both are

205、 funded by the International AIDSVaccine Initiative.Since there are many commonmechanisms between AIDS and diseases such asmalaria,tuberculosis,cancer and autoimmunediseases,the Units research has broad implicationsfor public health.MRC INSTITUTE OF ENVIRONMENTAND HEALTH(IEH)MRC is considering,in co

206、njunction with NERC,proposals from theUniversity of Leicester for the future of IEH.The aim is to expand the Institutes remit andestablish an active research programme fromexisting strengths and research expertise withinLeicester.Such research activities wouldcomplement the current and ongoing revie

207、wfunction of IEH.MARY LYON CENTRE Following a surveyof research community needs,MRC is takingforward plans for a new state-of-the-art mousefacility.This will provide high quality housingand breeding space as well as laboratories whereresearchers can identify,develop and study newmouse models of huma

208、n disease.The facilitywill offer leading edge expertise in mouse genetics/genomics to academicsthroughout the UK.MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200125MRC HGMP RESOURCE CENTRE/MRCMAMMALIAN GENETICS UNIT The MRCmicroarray programme,provided by the MRCHGMP Resource Centre and MRC Mammalian

209、Genetics Unit,has begun to distribute humanand mouse gene arrays to the academiccommunity free-of-charge.In addition theprogramme is developing the tools for,andtraining scientists to manage,interpret and sharedata accrued from microarrays.The investmentrequired to fabricate arrays with several tens

210、 ofthousands of genes represented is beyond thescope of most UK research groups and thecentralised service provided by MRC is in manycases the only route for many researchers toobtain access to array technology.The MRC mouse genome sequencingconsortium,co-ordinated from the MammalianGenetics Unit,is

211、 providing high-quality finishedsequence in regions where there is focussedresearch effort in the UK;it will provide at least50Mb of sequence into the public domain by2002.The consortium additionally took on 12small projects from the research communityduring 2000.MRC HUMAN GENETICS UNIT(HGU)New rese

212、arch at HGU in Edinburgh includes acollaborative pilot project in complex humangenetics,studying an isolated population inSardinia.Insights gained from the Sardinianpopulation are likely to be applicable to the UKpopulation cohort planned by MRC,and thework aims to provide proof-of-principle thatgen

213、etic factors can be identified for complextraits.The identification of such loci willprovide insight into the mechanisms underlyingdisease progression,as well as the developmentof new therapies and diagnostics.MRC LABORATORIES JAMAICAThe MRC Laboratories(Jamaica)weretransferred to the University of

214、West Indies atthe end of 1999.MRC has organised a workshopto be held in Jamaica in the summer of 2001 toreview progress and help advise on the futuredevelopment of the Sickle Cell Unit.UNIT QUINQUENNIAL REVIEWSDuring the year,the following MRCUnits/Groupswere reviewed:MRC Muscle and Cell MotilityUni

215、t,MRC Human Genetics Unit,MRC ProteinPhosphorylationUnit.Most work was judged toreach the highest standards in science.SPEND BY SCIENTIFIC AREA(ESTIMATED GROSS SPEND IN 2000/01)MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200127Opportunities for working in partnership withother Research Councils have

216、 been pursuedwith vigour over the last year.For example:METROLOGYEPSRC,working with MRC and BBSRC,launched an initiative aimed at tackling importantlife science research questions through newapproaches to the measurement and analysis ofimportant parameters in biological andbiomedical systems.This in

217、itiative will helpmeet the needs of the post genome era andForesight.EPSRC made eight awards in April2000.A second call was launched in the Autumn.MRC contributed to 50%ofthe funding of a project in Cambridge on mathematicalmodelling ofdisordered myocardial conduction in relation to arrhythmia.TISSU

218、E ENGINEERINGEPSRC,BBSRC and MRC funded acollaboration led by Professor T Hardinghamand Professor M Ferguson(ManchesterUniversity)with Professor David Williams,(University of Liverpool).This InterdisciplinaryResearch Collaboration in tissue engineering willfocus on cell behaviour relevant to clinica

219、lproblems in skin and wound healing,cartilage/disc repair and the repair andmodification of vascular tissue.It will have astrong commitment to the translation ofbasic research into clinical application.IMAGINGA joint EPSRC/MRC InterdisciplinaryResearch Collaboration was established in 2000,directed

220、by Professor of UCL,Manchester,MBrady(Oxford),for research on the genericproblems involved with extracting clinicallyuseful information from medical images andsignals.NANOTECHNOLOGYIn May 2000,MRC organised a workshop on“Nanotechnology in Biomedicine”to promoteawareness of this new field(manipulatio

221、n ofmaterials and structures at the atomic andmolecular level)and to discuss how and wheredevelopments might be applied more broadly inbiomedical research.The workshop wasattended by national and international scientistsand representatives from interested ResearchCouncils,charities and industry.In J

222、uly 2000,EPSRC,BBSRC,MRC,MoD andDTI issued a joint call for inter-disciplinaryresearch collaborations(IRColls)innanotechnology.Bids were expected to involvea broad range of disciplines such as materialsscience,chemistry,physics,biology,engineeringand applied mathematics across severalUniversities.Si

223、xteen outline bids were receivedFive full proposals are being submitted and theoutcome will be announced in 2001.Working in partnership with other organisations continues to be an important component of MRCstrategy,where it is clear that mutually beneficial outputs will be generated.Partnership work

224、ing withindustry is covered in Chapter 5.Other key examples from 2000/2001 follow.PARTNERSHIPS3MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200128CHEMICAL BIOLOGYMRC and EPSRC issued a joint highlight noticeduring the year encouraging applications in thearea of chemical biology relevant to humanhealt

225、h.Successful applications may be part funded by EPSRC if relevant to theirscientific remit.SYNCHROTRON RADIATIONThe new synchrotron,“Diamond”,is to beconstructed at the Rutherford AppletonLaboratories,Oxfordshire.MRC has beenworking with the other Research Councils tosupport OST in taking the projec

226、t forward inpartnership with the French Government andthe Wellcome Trust.The Scientific AdvisoryCommittee to Diamond,chaired by Dr RichardHenderson(MRC Laboratory of MolecularBiology)has agreed that the new synchrotronwill be a 24 cell,3.0 GeV machine,and thatthere will be 7 beamlines available from

227、 day one,half of which will be for the life sciences.TheMRC is developing plans,in consultation withother Research Councils and funding agenciesand the scientific community,for the researchfacilities associated with Diamond.BIOINFORMATICSBioinformatics is playing an increasingly keyrole in facilitat

228、ing life sciences researchencompassing cellular to whole organism andpopulation studies.In June 2000 the ResearchCouncils held a workshop to examine the keypriorities for future research in bioinformaticsand to inform the community about developingcomputing infrastructure in the UK,known as“the Grid

229、”.The workshop recognised that asmall,high quality bioinformatics researchcommunity had been established in the UK,working at the interface between biology andcomputer science,which needed to besupported,expanded,and developed.MRCcontinues to strengthen training inbioinformatics by supporting 10 PhD

230、studentships,10 PhD+linked Mastersstudentships,15 Masters studentships,6 SpecialTraining Fellowships(1 jointly with PPARC),1Research Fellowship,1 Clinical TrainingFellowship and 1 Career Development Award.The Research Councils and Wellcome Trust nowmeet regularly to exchange information onbioinforma

231、tics via a“Funders Forum”whichaims to provide a“one-stop-shop”for advice onfunding opportunities in this field.In November 2000 the MRC and BBSRC jointlyfunded“CCP11”a collaborative computationalproject focusing on DNA sequence and proteinstructure informatics,hosted by the MRCHGMP Resource Centre a

232、nd aimed atsupporting software developers.The Research Councils issued a joint call for newBioinformatics Groups last year and EPSRCreviewed full applications in July 2000.Fourawards were made-to Oxford,Manchester,Imperial College and UCL.NEUROINFORMATICSThe MRC and BBSRC recently held a workshopon

233、neuroinformatics.Council agreed that this isan important area for further development,which will foster links between neuroscientistsand computer scientists,and that the fieldshould remain a training priority.In parallel,MRC is contributing to the work of theOrganisation for Economic Co-operation an

234、dDevelopment in neuroinformatics,whichincludes the establishment of a web-basedresource site and the development of databases.SMALL BUSINESS RESEARCH INITIATIVEThe Small Business Research Initiative(SBRI)was announced in the Science and InnovationWhite Paper in July 2000.It aims to increasedemand fo

235、r research and development fromsmall and medium sized enterprises.TheResearch Councils are collaborating to developthis scheme,in consultation with the OST andpublished details on their respective Web sitesand on a central SBRI Web site early in April 2001.MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000

236、 200129HEALTH OF THE PUBLIC The MRCs Health of the Public initiative aimsto expand the UKs capacity for research into thedevelopmental,environmental and socio-economic factors affecting health and healthinequalities and to strengthen research intointerventions.A second tranche of 14 awardswas made i

237、n 2000.To promote training in thisarea,the MRC and NHS R&D Directoratecontinue to fund research fellowships throughthe MRC Health Service Research FellowshipScheme.Two new awards were funded in 2000via the Health Departments allocation to theCommittee for Epidemiological Studies of Aids(CESA).A high

238、light notice for new CESAapplications,in January 2001 is generatingsignificant interest.AUTISM At the request of the Department of Health,theMRC has set up a Review Group to look into thekey questions in understanding the incidence,causes and biomedical treatments for autism.The Review Group will in

239、clude representativeconsumers,charities,practitioners and expertscientists and will meet over the Summer of 2001.NICOTINE REPLACEMENT THERAPY(NRT)The Department of Health will be workingclosely with the MRC to take forward researchinto smoking cessation through the use of NRT.There are a number of k

240、ey areas where theefficacy of NRT is still to be evaluated and theMRC will provide expertise in carrying forwardresearch in these areas.TRANSMISSIBLE SPONGIFORMENCEPHALOPATHIES (TSEs)The MRC has developed a broad portfolio ofresearch into TSEs,co-ordinated with otherfunders.TSE remains a priority ar

241、ea,a keyobjective being the expansion of the portfolio,in particular in the areas of diagnostics andtherapeutics,by attracting young and newresearchers to the field.MRC has taken the leadon two initiatives,a meeting between keyacademics and representatives from theENVIRONMENT AND HEALTHMRC and NERC

242、continue to welcome proposalsunder this joint initiative.It is aimed atencouraging research into the human healthimpacts of environmental exposures,specificallythrough collaboration between environmentaland medical scientists.Three Co-operativeGroup grants have been awarded in the areas ofglobal env

243、ironmental change,air pollution andthe role ofenvironmental factors inMycobacterium transmission in Crohns disease.MRC continues to work closely with the NHSand Health Departments at a number of levelsacross a range of shared interests.Devolutioncoupled with the Governments appointment ofCzars in ke

244、y health areas has provided newopportunities.Developments in key priorityareas included:FUTURE OF THE MRC GENERAL PRACTICERESEARCH FRAMEWORK(GPRF)The GPRF is a network of over 1000 generalpractices throughout the UK providing access toover 10%of the population;it is a nationalresource that facilitat

245、es many different clinicaland epidemiological studies.During the year,Council gave consideration to the future locationof the GPRF Co-ordinating Centre,beyondclosure of the MRC Epidemiology and MedicalCare Unit,where it is current located.It hasbeen agreed that the GPRF Centre should berelocated to

246、the MRC Clinical Trials Unit atUniversity College,London.PRIMARY CARE RESEARCH A total of ten strategic grants,including twoprogramme grants and five trial grants,weresupported under the first round of the jointMRC/DH initiative on Primary Care Research.A second call for proposals was issued in theS

247、pring of 2000 with a view to making furtherawards in early 2001.PARTNERSHIPS WITH THE NHS ANDHEALTH DEPARTMENTSMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200130diagnostics industry,followed by a call forproposals on the development of diagnostictools.The meeting,in February 2001,successfully highli

248、ghted the difficulties the field isfacing and the problems that remain unsolved inan effort to try and encourage more industrialinvolvement.The joint TSE Research FundersWorkshop took place at Keele University in April2000 when grant holders presented their latestresearch findings.The Funders are wo

249、rkingtogether to ensure efficient arrangements toprovide researchers with clinical and animalmaterial and other valuable TSE reagents.An expert MRC/DH Steering Group ismonitoring three DH funded studies aimed atdetermining the potential scale ofvCJDinfection in the UK population.These studiesare exa

250、mining around 20,000 samples of tonsilor appendix tissue,discarded after routineoperations,for tell-tale signs of abnormal prionprotein.During the year a preliminary analysis of3,170 tonsil samples found no evidence ofabnormal prion protein,however thisencouraging result must be treated with caution

251、.It is not possible to predict the level of vCJDinfection in the population from these data,because the sample size is small,the incubationperiod of the disease is unknown and it is notknown whether everyone with a positive testwould necessarily go on to develop the disease.However,the results will

252、inform the design offuture surveys and the situation may becomeclearer when further samples have beenanalysed.The difficulties analysing the datahighlight the need to develop a non-invasive,pre-clinical,vCJD test for widespread screening.MOBILE TELECOMMUNICATIONS ANDHEALTH RESEARCH PROGRAMMES An Ind

253、ependent Expert Group on MobilePhones(IEGMP),commissioned by theGovernment and led by Sir William Stewart,looked last year,at the potential effects ofmobile phone technology on health;itscrutinised recent research,took evidence fromscientists and listened to the views of the publicat open meetings a

254、round the UK.The IEGMPreport to Government recommended theestablishment ofa UK-based researchprogramme.The report of the House ofCommons Science and Technology Committeeon mobile phones and health made a similarrecommendation.Funds to support such aninitiative were attracted from industry andmatched

255、 by Government;MRC provided600k towards the 7m raised.The programmehas been set up as a LINK collaborative researchprogramme.The first call for proposals wasissued in February 2001 and a second call isplanned for September;the outcome will beknown later this year.MENTAL HEALTH The Council discussed

256、future strategy in thisarea at its residential meeting in February 2000 taking account of presentations from ProfessorLouis Appleby the DH Mental HealthNational Service Framework(NFS)Director and other experts.A number of areas wereidentified that will be carried forward by theMRC to potentiate ment

257、al health research inclose co-operation with both the Department ofHealth and the NHS,especially in providing theevidence for successful implementation of theNational Service Framework for Mental Health.These plans will build on existing MRC expertiseand infrastructures such as the General PracticeR

258、esearch Framework and the MRC Clinical TrialsUnit.CANCER A new national Cancer Research Institute(NCRI)will be launched in April 2001;it is thefirst national research institute in the UK tofocus on a specific disease and will oversee allaspects of cancer research including clinicaltrials of new trea

259、tments and genetics.Buildingon the work of the Cancer Research FundersForum(p30)the NCRI will bring together allUK Health Departments,the MRC,the CancerResearch Campaign,the Imperial CancerResearch Fund,the Ludwig Institute for CancerResearch,the Marie Curie Research Institute andthe pharmaceutical

260、industry.The NCRI will bechaired initially by Sir George Radda and will bebased at MRC Head Office;it will not fundinitiatives directly,instead the constituent bodieswill use their own budgets to fund initiativeseither singly or collaboratively.MEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200131The C

261、ouncil has also been asked by the MoD toadvise on the feasibility ofa prospectiveepidemiological study of service personnel whoparticipated in trials at Porton Down between1939 and 1989.DEPARTMENT FOR INTERNATIONALDEVELOPMENTThe joint scoping study,commissioned by MRCand the Department for Internati

262、onalDevelopment to identify new areas where theCouncils portfolio of research relevant todeveloping societies might be expanded,hasnow been completed.A review of HIV vaccinestrategies has also been carried out.Both reportswill be discussed by the Strategy DevelopmentGroup and Council later in 2001.M

263、RC GUIDELINES ON VACCINEDEVELOPMENT FOR EARLY PHASE TRIALSMRC is taking the lead in developing guidelinesfor academics who wish to take bench researchon vaccines through to early phase clinical trials.A working party was established last year,chaired by Professor Sir Leszek Borysiewicz(Cardiff;now I

264、mperial College,London)thatincludes representatives from the DH,Medicines Control Agency,National Institutefor Biological Standards and Control,Department for International Development,Centre for Applied Microbiology and Research,the Edward Jenner Institute for VaccineResearch,Industry,BBSRC and pro

265、tagonists fromthe research community.The draft guidelines willbe posted on the MRC Web page during 2001 withan invitation to comment.AGEING RESEARCHMRC,EPSRC,BBSRC,EPSRC and DHestablished last year a Funders Forum for AgeingResearch that brings these agencies together withthe major charities that fu

266、nd research in this area:A consortium involving the MRC Clinical TrialsUnit and groups at Leeds and York Universitieswill contribute to the National Cancer ResearchNetwork(NCRN)as one arm of the NCRN Co-ordinating Centre.These groups will operate anetwork for clinical trials and other research,such

267、as promising new approaches to thediagnosis,treatment and care of cancer patients.ANTIBIOTIC RESISTANCE In December 1999 and March 2000,Councilmade the first awards resulting from a webHighlight Notice on Antibiotic Resistance.Seven strategic grants have been awarded andsix further proposals are bei

268、ng reviewed.WORKING GROUP ON FLUORIDE ANDHEALTHA review from the NHS Centre for Reviews andDissemination noted that much of the evidencein the area of fluoride and health was of lowquality,following this,the DH asked MRC toestablish a working group to consider whatfurther research might be required.

269、The workinggroup met for the first time in February 2001.MINISTRY OF DEFENCEThe MRC continues to act as an independentadviser to the Ministry of Defence(MoD)onGulf War Illness Research.During the year,theexisting Steering Committee was succeeded by aGroup charged with reviewing evidence forGulf War

270、Syndrome and developing strategicadvice;it was further agreed that researchproposals in this area should be reviewed by therelevant Research Board(s).In May 2000 thePhysiological Medicine and Infections Boardapproved an award to Professor Simon Wesselyand colleagues(Kings College,London)for athree y

271、ear follow-up study ofGulfWar veterans;this work was funded by the MoD.PARTNERSHIPS WITH OTHER GOVERNMENTDEPARTMENTSPARTNERSHIPS WITH MEDICAL RESEARCHCHARITIESMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200132Alzheimers Society,and British Heart Foundation,Stroke Association,Joseph Rowntree Foundati

272、on,Research into Ageing,Anchor Trust,WellcomeTrust,Nuffield Foundation,the other healthdepatments and OST.The Forum,which is chairedin the first instance by Professor Sir John Pattison(Director of R&D at the Department of Health(England),met for the first time in October 2000;it provides an opportun

273、ity for memberorganisations to discuss matters of mutual interestand to identify areas where joint working couldmake a greater impact and maximise value formoney.MRC has commissioned,as part of theForums workplan,a bibliometric analysis of ageingresearch.Professor Ian Philp,the Governmentsnewly appo

274、inted National Director for OlderPeoples Services has recently joined the Forum.CARDIOVASCULAR DISEASEThe MRC recently helped establish theCardiovascular Research Funders Forum,whichwill consider areas of mutual interest relating tocardiovascular disease that would benefit from aco-ordinated approac

275、h.It is envisaged that theForum will help develop a concerted researchstrategy,foster future partnerships betweenresearchers and their funders,and facilitate theexploitation of the research to develop newapproaches to diagnosis and treatment.Membership of the Forum comprises seniorrepresentatives fr

276、om the British HeartFoundation,Diabetes UK,the MRC,theWellcome Trust,the Health Departments,andthe National Director for Heart Disease;it ischaired by Sir Charles George(BHF).The firstmeeting took place in January 2001.CANCERDuring 2000,the MRC carried out a review ofprostate cancer in the UK on beh

277、alf of theCancer Research Funders Forum which was setup in 1999,under initial MRC chairmanship.The main recommendation from the review wasthat the UK should begin to generate criticalmass in this area and to this end,the MRC,inpartnership with DH,CRC and ICRF hasrecently established two CRFF Prostat

278、e CancerCollaborative Groups.In addition to fulfilling ageneral research need,these Collaboratives havealso been tasked with networking the wider UKprostate cancer community,pump primingdevelopmental research and bridging the gapbetween basic and clinical research.Other work being undertaken by the

279、CRFFincludes the development of a national strategyfor tumour banking with a view to creating anational generic tumour bank.HUMAN DNA COLLECTIONSThe risks of developing many common diseasessuch as cancer and cardiovascular disease areaffected by a complex interplay between geneticpredisposition and

280、exposure to environment andlifestyle risk factors.The sequencing of thehuman genome and advances in technology fordetecting variations between individuals opensup exciting possibilities for identifying themultiple genetic factors involved andunderstanding how they interact.Large collectionsof DNA sa

281、mples associated with high qualityclinical and environmental data are essential forsuch studies.In October 2000 we funded 14 largeDNA collections from cohorts of patients andcontrols,selected from over 150 outlines.Thesewill underpin genetic research in commonconditions such as breast cancer,colorec

282、tal cancer,Parkinsons disease and depression.They include aheart disease collection which builds on a projectfunded by the British Heart Foundation,a diabetescollection which extends work started by DiabetesUK,and a glomerulonephritis collection which isa funding partnership with the National Kidney

283、Research Fund.As part of this initiative MRC plans to set up anational network of banking facilities to storethese collections,organise their distribution toresearchers,and manage the databases ofgenetic information obtained from researchusing the samples.It is also intended that thesecentres will a

284、ct as a foci for developing andevaluating new technologies for high throughputgenotyping.In December 2000 a call was issuedfor outline expressions of interest from centreswishing to participate in this network.Fullproposals will be invited later in 2001.In orderto promote better collaboration betwee

285、nMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200133scientists and more efficient use of resourcesMRC and the Cancer Research Campaign havejointly developed a database ofexistingcollections of human samples,which will beaccessible via the internet.This will bepublished later this year.Throughout the

286、year MRC and the WellcomeTrust,together with the Department of Health,have continued to develop plans for a new largeprospective UK population cohort involvingaround 500,000 adult volunteers.All threeorganisations have now agreed in principle tosupport this study.Consultation with a widevariety of p

287、otential stakeholders,including thepublic,NHS health and information technologyprofessionals,government departments,theHuman Genetics Commission,medical researchcharities,industry and the other researchCouncils,as well as the scientific community,isan important feature of the development of thiscomp

288、lex project.The results of an initial phaseof qualitative research on public attitudes,jointlycommissioned by the MRC and the WellcomeTrust,and carried out by Cragg Ross Dawson,were published in September 2000 and areavailable on the Website.CLINICAL TRIALSMRC has continued to build on its links wit

289、h thecharities in the assessment and funding ofclinical trials.Members of the Association ofMedical Research Charities are now routinelyconsulted on new outline applications in theirareas of interest to confirm whether theycurrently support or are planning to fund similarstudies or contribute to the

290、 trial in question.MRC is planning an informal meeting of TrialSteering Committee Chairmen and otherinterested parties to share experiences,problemsolving and refining/developing policy.INTEGRATIVE BIOLOGY A NEW APPROACHTO HEART DISEASEThe MRC has continued to work with the BritishHeart Foundation t

291、o develop an initiative inintegrative biology which will encourage newresearch to address the burden of heart disease inthe UK.The aim,in the first instance,is to establisheither a directly-supported Unit,or an indirectly-supported Centre within a University environment.An International Advisory Com

292、mittee has beencharged with identifying a Director of exceptionalability and international standing.Science is global and the MRC attaches highpriority to international collaborations,whichare facilitated by joint working with internationalbodies and national agencies from othercountries.The MRC has

293、 a lead role,in partnership with theDepartment of Health and other ResearchCouncils,in developing the UK policy in relationto the biomedical aspects of the EC Frameworkprogrammes.The MRC is responsible for the UKcontribution and input to a number ofinternational biomedical organisations,includingthe

294、 European Molecular Biology Laboratory(EMBL)and the European Molecular BiologyConference(EMBC)in Heidelberg,theInternational Agency for Research on Cancer(IARC)in Lyon,and the Human FrontierScience Program(HFSP)and European ScienceFoundation(ESF)in Strasbourg.The UKsubscription to these organisation

295、s is 5.5mp.a.and MRC is responsible for ensuring themaximum return to UK and internationalscience from this investment.Framework VFour rounds of proposals have now beenconsidered for funding under the“Quality ofLife and Management of Living Resources”(QoL)life sciences programme of Framework Vand th

296、e UK academic community is continuingto attract substantial funding.MRC Units,inparticular,have been very successful and are nowinvolved in more than 60 major Europeanprojects and training networks,funded underFPV,with about a quarter of these projects alsobeing co-ordinated by MRC scientists.INTERN

297、ATIONAL PARTNERSHIPSMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200134Biology Laboratory(EMBL);MRC manages theUK contribution.To prepare for the DirectorGenerals new research proposals and indicativebudget for 2001-2005,MRC set up amultinational review of EMBL that reported toMRC Council in October

298、2000.The reportinformed the UKs funding decisions whichwere transmitted to EMBL Council inNovember 2000;decisions taken by EMBLCouncil,which had to be unanimous,will meanthat the UK contribution will increase by 1mper annum to 5m per annum.A significantproportion of this overall increase will bedire

299、cted towards the European BioinformaticsInstitute in Hinxton.EMBL Council also agreedto start planning for the appointment of theDirector Generals successor when ProfessorKafatos retires in 2005,and the future shape ofthe EMBL portfolio.EUROPEAN MOLECULAR BIOLOGYCONFERENCE The MRC is also responsibl

300、e for the UKcontribution to the European Molecular BiologyConference(EMBC)in Heidelberg and isrepresented on a newly constituted EMBCStrategy Group.Council has agreed tocontribute additional funding to a new EMBOYoung Investigator Award Scheme,which willafford key networking opportunities toestablis

301、hed groups in member states.THE HUMAN FRONTIER SCIENCE PROGRAM(HFSP)HFSP is an inter-governmental organisationwhose mission is to promote inter-continentalcollaboration in interdisciplinary,basic researchin life sciences.It provides funding forcollaborative research projects and a range ofprestigiou

302、s Fellowships.MRC,and to a lesserextent BBSRC,are responsible for the UKcontribution to HFSP.During last year wecarried out consultation with UK researchers toassess the value ofthis contribution.Negotiations over the future level of funding bythe UK and other member states will be ongoingduring 200

303、1/2.This review will provide the basisfor budget discussions with the HFSP Board ofTrustees during the coming year.MRC is represented on the ProgrammeManagement Committee(PMC)and MRCofficers continue to act as national contact pointand to advise UK scientists on proposals forQoL under FPV.Via the PM

304、C,the MRC hashad an influence this year on EC discussions inseveral areas,including EC support for theEuropean Bioinformatics Institute,TSEresearch and a new initiative in genomics andhuman health.Framework VIThe MRC,together with the other UK ResearchCouncils and relevant GovernmentDepartments has

305、been actively involved in theconsultation exercise conducted by OSTfollowing publication of the EC policy paper“Towards a European Research Area”in January2000.This provides the context in which theformal EC proposal for the next Frameworkprogramme was published in February this year.One of the them

306、atic priority areas for thisprogramme is“Genomes and Biotechnology forHealth”and biomedical research is also includedin several other thematic areas.Work has nowbegun on defining the specific content of thesethematic programmes and MRC will continue toplay a role in their development.One area of par

307、ticular interest to MRC inrelation to the next Framework is the proposednew initiative on the major diseases of poverty AIDS,TB and Malaria.This was launched at aHigh Level Round Table Meeting held inBrussels in September 2000,attended by SirGeorge Radda.In the light of MRCs experiencein research on

308、 these infectious diseases andsubstantial investments in Africa,we have beendiscussing with the EC and other potentialpartners development of a concerted Europeanapproach.This initiative is timely in light of theincreased interest of the G8 countries in globalpoverty and the Cabinet Office review of

309、 thisarea initiated late in 2000.EUROPEAN MOLECULAR BIOLOGYLABORATORYThe UK is one of 16 member states thatcontribute funding for the European MolecularMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200135STRENGTHENING INTERNATIONALPARTNERSHIPSClinical TrialsMRC has developed a programme ofcollaboratio

310、n with the US VeteransAdministration and the Canadian Institutes ofHealth Research to encourage proposals thataddress health care questions of commonconcern.Through access to a much larger poolofpotential participants than is availablenationally,the initiative allows studies to becompleted more quic

311、kly than would otherwisebe the case;it also promotes best practice in trialdesign,execution and management andmaximises the effectiveness of the investment ofthe three funding bodies.The first study to befunded under the collaboration,a trial of newclinical management strategies for HIV patients(OPT

312、IMA),will be launched in March.Much needs to be done to facilitate the conductof multi-national trials.To this end,the MRCClinical Trials Unit hosted an ESF workshop on“Challenges in Developing pan-EuropeanClinical Trials”in September 2000.Several verypositive recommendations came out of thisworksho

313、p and discussions are taking place withESF as to how these might be taken forward.One of the major problems identified was therestrictive conditions for conducting publiclyfunded European Trials that would be imposedby the new EC Directive on the conduct ofclinical trials on medicinal products.ThisD

314、irective will potentially also make trials farmore expensive.MRC and DoH are workingclosely with the Medicines Control Agency toensure that views of public funders and theacademic community are represented in thetransposition of the Directive into UK lawMRC is committed to the development of aninter

315、national meta-register ofrandomisedcontrolled trials.We are working with thecompany Current Controlled Trials(CCT)todevelop the register and implement a system ofunique identification numbers for tracking trials.The register will not only assist in the planningofnew studies,but will also help avoidu

316、nnecessary duplication,encouragecollaboration,facilitate patient access toinformation and help reduce the problem ofpublication bias.To this end,a uniqueInternational Standard Randomised ControlledTrial Number(ISRCTN)has now been assignedto the majority of MRC trials.Henceforth thisnumber will be us

317、ed in all aspects of trialmanagement and documentation,including anypublications that arise from the study.Withadvice from MRC,CCT are preparing a proposalto the EC FPV programme to extend theirregister and the ISRCTN concept to otherEuropean countries;discussions have also takenplace with ESF.GOOD

318、CLINICAL PRACTICEMRC and DH have been working with theMedicines Control Agency to ensure that theperspectives of public funders and the academiccommunity are represented in the framing of thenew European Directive on the implementationof good clinical practice in the conduct ofclinical trials on med

319、icinal products.Now thatthe Directive has been adopted,MRCsinvolvement will continue in helping to draft theaccompanying guidelines for the Directive andadvise on its transposition into UK law.The Max-Planck-Gesellschaft(MPG)During the year,there have been several reciprocalvisits between senior Off

320、icers of the MRC and theMPG.This exchange of practice has been veryinformative at an operational level.At a scientificlevel we are optimistic that these contacts will alsolead to closer collaborations and we are noworganising a bi-lateral young investigators workshopin Developmental Neurobiology,whi

321、ch will takeplace later this year.We hope that this will be thefirst of a series of such topic-based workshops thatmight expand to encompass other fundingagencies.Institut PasteurIn January 2001,a meeting took place betweenMRC and the Institut Pasteur,Paris to discussopportunities for bi-lateral col

322、laboration.TheInstitut Pasteur is potentially a key partner in theproposed EC initiative on the diseases ofMEDICAL RESEARCH COUNCIL ANNUAL REPORT 2000 200136poverty(see Framework VI above).Severalother scientific areas,including technologydevelopment were identified where further bi-lateral explorat

323、ory workshops might beproductive.These will be taken forward duringthe course of the next year.CNRSFollowing an MRC/CNRS meeting on mousegenomics in Paris in 1999,there was agreementto co-ordinate,at a bi-lateral level,thedevelopment of and access to mouse genemicroarrays.The first meeting ofa co-or

324、dinating committee took place in Paris in May2000,and a further meeting was held in earlyMarch 2001 at MRC in London.The meetingsare co-chaired by Professor Radda and ProfessorGodet,Director of Life Sciences at CNRS,andthe co-ordinating committee consists of seniorscientists and administrators from

325、bothcountries.A key development has been thesharing of knowledge and resources,particularlywith respect to cDNA libraries.National Institutes of Health(NIH)There have been several meetings betweensenior MRC Officers and NIH InstituteDirectors.This has included two visits byProfessor Radda to NIH in

326、Washington.We areexchanging ideas and co-ordinating our activitieswith NIH in a number of important areasincluding cardiovascular disease,cancer andtropical medicine.In recognition of the ever increasing power ofcomputers and the potential impact ofcomputational modelling on biomedicalresearch,MRC a

327、nd the US National Institute forGeneral Medical Sciences have been workingtogether to co-sponsor a workshop onComputational Cell Biology which will takeplace in June 2001.The aim of the workshop isto bring together key figures in the field,topromote awareness of new developments anddiscuss where suc

328、h developments might beapplied more broadly in biology and medicine.Number and Value of formal international collaborative projects:1997-981998-991999-002000-01NomNomNomNomI IN NT TE ER RN NA AT TI IO ON NA AL L C CO OL LL LA AB BO OR RA AT TI IV VE E P PR RO OJ JE EC CT TS S (n nu ummb be er r a an

329、 nd d iin nc co omme e)EC1142.71363.21433.71274.1UN(including WHO,IARC)110.3170.4110.640.2Others(including HFSP,ESF,NATO,EMBO)260.3360.5370.5400.7Other international agreements(including governments,charitiesand industries)782.3851.9822.8713.2Total2295.62746.02607.62428.2MEDICAL RESEARCH COUNCIL ANN

330、UAL REPORT 2000 200137Imaging Research Solutions LtdIn February 2001,Nycomed AmershamImaging(NAI)and MRC announced a strategicjoint venture to form Imaging ResearchSolutions Ltd(IRSL),a leading molecular levelimaging centre at Hammersmith.This uniquepartnership between the public and privatesector h

331、as been formed to leverage theopportunities presented by the increasinglyimportant applications of Positron EmissionTomography(PET)to the pharmaceuticalindustry and in clinical diagnosisHigher Education Funding CouncilOver the last year,MRC contributed views to theevidence-based review ofthe Researc

332、hAssessment Exercise(RAE);topics debated inthe review included research funding and policy.MRC is also participating,with observer status,in the current RAE review of the Universities.Human Genetics CommissionAs reported last year,MRC has established a newAdvisory Committee on Scientific Advances in

333、Genetics(ACSAG)chaired by Lord Patel.TheCommittee has regular contact,and cross-membership with the Governments advisorybody in this area,the Human GeneticsCommission.Major areas of discussion for theCommittee so far include pharmacogenomics,stem cell biology,and risk perception.Office of Science and Technology-ForesightProgrammesMRC contributed to the priority setting of six ofthe thirteen Foresi