Issue 11 University of Cambridge Research Horizons

HORIZONS

University of Cambridge research magazine www.research-horizons.cam.ac.uk

Issue 11 | Spring 2010

In this issue

CANCERplus news and views from

across the University

RESEARCH

eDitoRiAL

A warm welcome toResearch horizonsmagazine. this issuewe focus on cancer –a significant researchtheme across manydepartments in theUniversity and a

clinical and healthcare strength withinthe Cambridge University hospitalsnhS foundation trust.

in the past decade, over £70 millionhas been invested in new cancerresearch buildings and facilities inCambridge, including the CancerResearch UK Cambridge Researchinstitute (CRi)/Li Ka Shing Centre, theStrangeways Research Laboratory andthe hutchison/medical ResearchCouncil Research Centre, as well as innew clinical facilities for cancer patients;and annual cancer research funding inCambridge now exceeds £40 million.Professor Sir Bruce Ponder, featured onour front cover, leads the CRi, whichhosts 250 scientists working within 21 research groups and is one of theprincipal cancer research facilities ineurope.

We hope that our Spotlight sectiongives a sense of the partnerships thatare proving vital for translating cancerresearch into real benefits for patients:from understanding the fundamentalbasis of cancer, to identifying thoseindividuals with the highest risk; andfrom diagnosing and treating cancerearly, to moving towards tailoredtreatment and monitoring of patients.helping to connect this researchcommunity, a virtual Cambridge CancerCentre was launched in 2006 byProfessor Ponder to promoteinteractions between researchers andclinicians working in diverse areas toachieve the best possible results forcancer patients.

elsewhere in this issue, we bringyou examples of some of the otherremarkable research happening acrossthe University, in areas as diverse as theswine flu pandemic, how Britainbecame an island nation, handwritingin 500-year-old manuscripts, dyslexiaand dyscalculia, the purity and linguisticcorrectness of the french language,and the publishing of bestsellers.

if you have any comments andsuggestions for future issues, pleaseemail them to me [email protected]

Dr Louise Walsheditor

Contents

Research News 3–7

Spotlight: Cancer 8–19Cambridge Cancer Centre: the vision 8Beacons of life and death: chromatin and cancer 9Cancer: what’s on the cards? 10Understanding how cancer cells grow 12Data mining the complex cancer landscape 13Smart testing for smart drugs 14Watching cancer cells eat, breathe and die 16Cut-and-paste cancer: lymphoma’s genetic blueprint 17Hutchison/MRC Research Centre 18

Knowledge Transfer 20–21

Preview 22–23 The future of books

Features 24–31 Britain’s island heritage: reconstructing half a million years of history 24A scriptorium of commonplace books 26Le bon usage: using French correctly 27From pandemic to policy: combating swine flu 28The educational neuroscience of dyslexia and dyscalculia 30

In Focus: The British Academy 32–33

Inside Out: Professor Jaideep Prabhu 34

Forthcoming Events 35

The Back Page 36Your way into Cambridge

From pandemic to policy:combating swine flu

Watching cancer cells eat,breathe and die

Cover photograph of Professor Sir Bruce Ponder.Edited by Dr Louise Walsh.Designed by Cambridge Design Studio (www.cambridgedesignstudio.org).Printed by Falcon Printing Services Ltd (www.falcon-printing.co.uk).©2010 University of Cambridge and Contributors as identified. All rights reserved.

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2 | issue 11 | Spring 2010

issue 11 | Spring 2010 | 3

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Professor Lynn gladden is one of theUniversity’s five Pro-vice-Chancellors,whose role is to take forward strategyand policy development and tosupport the vice-Chancellor inproviding institutional leadership forthe University, particularly in theirareas of responsibility. the Pro-vice-Chancellors work closely with theheads of Schools and seniorprofessional administrators. As Pro-vice-Chancellor for Research, Professorgladden succeeds Professor ian Leslie.

Professor gladden CBe, fRS,fReng is the Shell Professor ofChemical engineering, and head ofthe Department of Chemicalengineering and Biotechnology. She isalso a member of the Council of theengineering and Physical SciencesResearch Council (ePSRC). Professorgladden was awarded a CBe in theQueen’s Birthday honours list in June2009 for services to chemicalengineering, having been awarded anoBe in 2001 for services to chemistry.her particular research interests are inapplying magnetic resonanceimaging techniques in the fields ofheterogeneous catalysis and multi-phase transport in porous media.

Professor Lynn Gladden:Cambridge’snew Pro-Vice-Chancellor forResearch

funding from the Wellcome trust (Wt)and medical Research Council (mRC) hasbeen announced for a £5 millionresearch programme on Alzheimer’sdisease (AD) in Cambridge. theprogramme, which is led by ProfessorPeter St george-hyslop in theCambridge institute of medical Researchand Department of Clinicalneurosciences, is a major collaborativeeffort involving 15 scientists from sevenresearch departments across Cambridge.the programme also involves scientistsfrom the University of Bristol, the maxPlanck Centre for Structural molecularBiology in germany and the University of toronto in Canada.

AD is an increasingly commonneurodegenerative disease of the brainthat affects individuals in mid-to-late life,impairing intellectual function andmemory. the disease, which is incurable,results when certain proteins in the brainbecome misfolded and form tangledmasses that are toxic. the resultingprogressive loss of cells in the braingradually incapacitates patients for up toa decade before death. the incidence ofAD is on the increase as populations livelonger: in the UK, 700,000 peoplecurrently live with dementia, half ofwhom have AD; in 30 years’ time, theestimates are that this number will havehit 1.4 million and be costing the UKeconomy £50 billion per year.

Professor St george-hyslopexplained the unique challenge thedisease poses: ‘Although AD has beenknown about for over a century, it’s sucha complex disease that attempts tounderstand the underlying mechanismusing conventional tools have yieldedconfusing and conflicting answers. As aconsequence, there is currently no drugthat can halt its progression.’

to plug the gaps in knowledge, theinterdisciplinary research programmebuilds on a collaboration that has beengrowing for several years in Cambridge,as co-investigator Professor ChrisDobson from the Department ofChemistry explained: ‘A fascination withhow the fundamental molecular eventsthat underlie AD relate to what ishappening in living systems has broughttogether a group of people withinterests that range from theory totherapy.’ the consortium pulls inexpertise from biochemistry, genetics,clinical neuroscience, medical genetics,chemistry, chemical engineering,neurophysiology, physics, biophysics and pathology.

the programme aims to lay the basis for both the development ofbiological markers to detect disease atan early stage, before widespreaddamage has occurred, and the creationof effective therapeutics. ‘Already, theconsortium is working well. theatmosphere takes alight as people throwin ideas about novel experimentalapproaches using tools from bothphysical and life sciences that would nothave been possible until very recently,’said Professor St george-hyslop.

Professor Patrick Sissons, head of theSchool of Clinical medicine and RegiusProfessor of Physic, added: ‘this initiativeexemplifies the power of collaborationbetween internationally leadinginvestigators who can look beyond theirindividual spheres, and work at theboundaries of traditional disciplines tobring new insight to a notoriouslycomplicated disease.’

For more information, please contactProfessor St George-Hyslop([email protected]).

New funding to untangle Alzheimer’sdiseaseA major new drive to understand, diagnose and treatAlzheimer’s disease has begun in Cambridge.

Brain of an Alzheimer’s patient (left), showing considerable cell loss, compared with a normal brain (right)

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in 1948, Cambridge academic ProfessorCharles mcBurney stumbled upon a largecave on the north coast of Libya.Returning to excavate it three years later,he sank a trench 14 metres into the floorof the cave, finding layer upon layer ofevidence of human occupation goingback thousands of years into deepprehistory.

over 50 years later, excavationresumed in 2007 when Professor graemeBarker, Director of Cambridge’s mcDonaldinstitute for Archaeological Research, ledan expedition of 30 academics from 10research institutes back to the haua fteahCave. now, mid-way through this five-yearproject, the researchers have made afascinating discovery that sheds new lighton when modern humans first arrived onAfrica’s northern shores.

‘mcBurney’s work was a seminalcontribution to world prehistory. Withtechniques available to him in the 1950s,he concluded that the trench spannedabout 80,000 years of history. he believedthe human jaws that he discovered deepdown were pre-modern in anatomy andthat modern humans (Homo sapiens)arrived in north Africa around 40,000 yearsago, which is about when they reachedeurope,’ explained Professor Barker. ‘theadvent of new technologies has enabledus to re-evaluate this. Already our findingsare showing that this site is probably farolder than mcBurney realised. the jaws arenow recognised to belong to Homosapiens, and we now have definiteevidence of our species being in northAfrica for at least 80,000 not 40,000 years.’

the team has painstakingly emptiedthe sediment that mcBurney used to re-fill

the trench, revealing the original walls ofthe pit. they have now reached a depth of10 metres, just below where the jaws werediscovered. Using dating technology suchas optical stimulated luminescence –which essentially measures the last time agrain of quartz saw the light of day – theresearchers have established that theyhave reached sediment that is 90,000 yearsold.

‘now that we have the first definiteevidence for our species being in northAfrica at least 80,000 years ago, thequestion is whether they were behaving inways we would recognise as modern. Weare looking for evidence of their

technologies and hunting practices andtheir level of cognition,’ explained ProfessorBarker. ‘And since we have another 6 metres to go before we hit bedrock, thedeepest archaeological trench in northAfrica has potentially a 200,000-year-oldstory to tell.’

For more information, please contact Professor Graeme Barker([email protected]), the DisneyProfessor of Archaeology. This researchwas principally funded by the EuropeanResearch Council, with supplementaryfunding from the Society of LibyanStudies, the project’s sponsor.

Evidence of the first modern humans in North AfricaExcavation of the deepest archaeological trench in North Africa half a century after it was firstdug is offering a glimpse of up to 200,000 years of human history.

the engineering and Physical SciencesResearch Council (ePSRC) hasannounced the investment of £13 million to fund three new CDts atthe Universities of Cambridge, Lancasterand Warwick. the new Centres will openat the beginning of the next academicyear and will each train at least 40students over seven years. each PhDstudent will develop an original researchproject and receive a formal programmeof taught coursework to broaden their

skills and enhance their technical andinterdisciplinary knowledge.

the Cambridge Centre for Analysis willbe directed by Professors Arieh iserles andJames norris. it will aim to build up coreexpertise in mathematical analysis withina cohort of some of the best youngmathematical minds in the world. trainingwill cover the full range of moderntechniques of analysis for mathematicalmodelling, spanning pure, stochastic,computational and applied analysis.

the Centre will provide opportunitiesfor fundamental research, team-basedproblem solving, industrial secondmentsand interdisciplinary collaboration. it will create a generation of independent-minded mathematical researchers whowill contribute to the long-termscientific, technological and economicwell-being of the UK.

For more information, please visitwww.maths.cam.ac.uk/cca/

Investing in the future of mathsA new Centre for Doctoral Training (CDT) in mathematical sciences will train the next generationof mathematical analysts.

Excavation of the Haua Fteah Cave, Libya, today (left) and by Charles McBurney in the 1950s (right)

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in an underground chamber at the‘remotest part’ of the University lies theUK’s largest centrifuge and the world’smost productive machine for observingand measuring geotechnical phenomena.Located at high Cross on madingley Road,the turner centrifuge at the Department ofengineering’s Schofield Centre travels atspeeds of 200 miles per hour and creates150 times the earth’s gravity. the 10 metrediameter centrifuge is being used tomodel loads and pressures experiencedduring earthquakes, and to simulatetunnels and wind farms.

now, thanks to funding from theeuropean Commission (eC), experimentscarried out in Cambridge will soon be‘talking’ to experiments happening at thesame time at sites across europe. Data willbe fed in real-time across the internet toother sites participating in the project,allowing multiple institutions to take part

in a common experiment. in all, 23institutions, each with its own specialistequipment, are involved in research aimedat answering questions about thebehaviour of shallow building foundationsin earthquakes.

the Seismic engineering Researchinfrastructures for european Synergies(SeRieS) project is being coordinated by Dr gopal madabhushi and Dr Stuart haigh.‘european seismic engineering researchhas tended to suffer from extremefragmentation of research infrastructuresand limited access to equipment betweencountries,’ explained Dr madabhushi.‘SeRieS answers this need by enabling thekey actors in europe’s seismic engineeringresearch, including three industrialbeneficiaries, to coordinate remoteresearch activities in real-time.’

the project builds on the success of a smaller-scale initiative between the

UK’s three leading earthquake engineeringlaboratories at the Universities ofCambridge, oxford and Bristol withfunding from the engineering and PhysicalSciences Research Council (ePSRC). thisshowed the benefits of creating real-time,grid-based communications to provideaccess to experimental facilities and data.

for SeRieS, the efficiency and cost-effectiveness of resource usage isconsiderable: it’s been estimated that the annual cost to the eC of the four-yearprogramme is less than 1.35% of the total present value (€190 million) of thematerial resources to be shared by the 23 participants.


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Earthquake research reaches across EuropeReal-time transnational access will enable researchers to participate in experiments all overEurope without leaving the lab.

Against stiff competition from over 100teams in top international institutions, theCambridge team was awarded the grandPrize at the 2009 international geneticallyengineered machine (igem) competitionfinals at the massachusetts institute oftechnology (mit) in november. As well aswinning the overall prize for best projectand the BioBrick trophy, the team wasawarded a gold medal and trophy for theBest environment Project.

the undergraduate students (vivianmullin, Alan Walbridge, Shuna gould,Siming ma, mike Davies, megan Stanleyand Crispian Wilson) faced the challengeof conceiving, designing andimplementing a synthetic biologicalsystem using standard, interchangeableDnA parts (‘BioBricks’) and operating it inliving cells.

their winning idea, ‘e.Chromi’, is basedon the engineering of bacteria that are

normally found in the gut, in order togenerate multicoloured pigments andprovide improved biosensors. onehypothetical application of the inventionwas explored with Daisy ginsberg andJames King from the Royal College of Art:the engineered bacteria could beingested as a probiotic to provide cheap, personalised disease monitoring.Chemical changes in the gastrointestinaltract caused by disease would result in a colour signal in faeces that is bright enough to be visible to the human eye.

the team was supported throughoutthe project by faculty staff from theDepartments of Plant Sciences, genetics,Pathology, engineering, and Chemicalengineering and Biotechnology. one ofthe advisors, Dr Jim haseloff from theDepartment of Plant Sciences, describedthe special role that the competition has

played inCambridge: ‘Since 2005,when Cambridge was the first UK team to take part in igem, the competition has brought together a network ofresearchers interested in the interplay of biology and engineering, helping tostrengthen the emerging field ofsynthetic biology in Cambridge. thecompetition is a highly motivating andeducational experience for all concernedand we’re delighted that the innovativeideas of this year’s team have been sowell received by the judges.’

For more information, please visitwww.synbio.org.uk/igem.html andwww.echromi.com/

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Cambridge wins Grand Prize for iGEM 2009A team of Cambridge students has been awarded the Grand Prize fortheir entry into an international synthetic biology competition.

For more information, please contactDr Gopal Madabhushi ([email protected]) or visit the SERIES website(www.series.upatras.gr/).


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finding an effective early way to diagnoseschizophrenia has been a long-termdream of Dr Sabine Bahn at theCambridge Centre for neuropsychiatricResearch, located in the Department ofChemical engineering and Biotechnology.for the past 13 years, Dr Bahn and herteam have been progressing towards agreater understanding of the molecularprocesses that lead to the disorder. todevelop the research, Dr Bahn foundedPsynova neurotech Ltd in 2005 with initialCambridge enterprise Proof of Conceptfunding, followed later by an investmentfrom the Cambridge enterprise Seedfunds.

now, an objective blood test for thediagnosis of schizophrenia is due to belaunched in 2010. this follows acollaboration between Psynova and Rules-Based medicine inc. (RBm) which recentlyled to the discovery and characterisation

of a combination of protein biomarkersthat can be used as an adjunctive aid inthe differential diagnosis of schizophrenia.on achieving this milestone, texas-basedRBm announced additional investments inPsynova and now has a controlling interestin the company.

‘While several psychiatric conditionsshare symptoms, the clinical interventionsvary, making it important to establish anaccurate diagnosis as early as possible,’explained Dr Bahn. ‘We intend to developa minimally invasive, objective test to aidthe early diagnosis of schizophrenia anddifferentiation from bipolar disorder andmajor depression.’

head of Seed funds at Cambridgeenterprise Dr geraldine Rodgers added:

‘Schizophrenia is a tough condition todiagnose and this discovery has thepotential to make a difference to thosewho suffer from this incapacitating disease.’ the two companies are workingwith leading psychiatric researchers togain additional clinical input to maximisethe benefit for patients and the healthcaresystem.

For more information, please contact Cambridge Enterprise Ltd (Tel: +44 (0)1223 760339; email:[email protected]) or visitwww.enterprise.cam.ac.uk/

New blood test for schizophreniaThe first objective means ofdiagnosing a disorder thataffects over 24 million peopleworldwide has been discovered.

New Regius Professor of BotanyCambridge has a new Regius Professor, after Her Majesty the Queen conferred the royal title on theUniversity’s existing Professorship of Botany.

the new Regius Professorship of Botanybrings the number of Regius Professors atCambridge to seven, joining Civil Law,Divinity, greek, hebrew and Physic (all

founded by henry viii in 1540) and modernhistory (founded by george i in 1724). historically, Regius Professorships werecreated by the Crown in disciplines judged

to be fundamental, and for which there isa continuing and significant need. thenew position links the University’s 800thAnniversary celebrations with the DarwinAnniversary in 2009 as J.S. henslow,Charles Darwin’s mentor, was Professor ofBotany at Cambridge.

Sir David Baulcombe is the first to holdthe new Regius Professorship of Botany.he was knighted in the 2009 Queen’sBirthday honours list for services to plantscience, and in 2008 was awarded theAlbert Lasker Basic medical Researchaward for his discovery of how smallmolecules of ribonucleic acid (RnA)govern gene activity through a processknown as RnA silencing. ProfessorBaulcombe’s research has unravelled howthis mechanism is important in generegulation and as a natural weapon inmechanisms of disease resistance anddefence against viruses in plants.

For more information about theDepartment of Plant Sciences andProfessor David Baulcombe’s research, please visitwww.plantsci.cam.ac.uk/research/

Cambridge’s Regius Professors: back row, from left, Sir David Baulcombe, Botany; Richard Hunter, Greek; David Ford, Divinity; David Ibbetson, Civil Law; front row, from left, Robert Gordon, Hebrew;Richard Evans, Modern History; Patrick Sissons, Physic

Dr Sabine Bahn (far right) and two member of her team


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over the next 10 years, a StrategicPartnership in Structural metallic Systemsfor Advanced gas turbine Applications willdevelop materials skills and knowledge tosupport the development of future gasturbines. it builds on a highly successfulUniversity technology Partnership fundedby Rolls-Royce between the Universities ofCambridge, Birmingham and Swansea.

fundamental materials research isneeded to develop materials that willimprove the efficiency and environmentalsustainability of gas turbines, whichprovide the power for many applicationsincluding aircraft, ships and electricitygeneration. Principal investigator Dr howard Stone, from the Department of materials Science and metallurgy,explained: ‘Dwindling resources andclimate change are forcing engineeringdesigners to utilise materials and energysupplies with ever-greater efficiency.

one approach is to find materials thatwithstand gas combusting at highertemperatures, since this uses less energyand creates less Co2.’

to meet this challenge, theprogramme brings together a critical massof researchers to increase the efficiency ofknown materials or to find new materialsthat can be used for the hottest parts ofthe engine. Cambridge’s contribution willbe to develop and test new structuralmetallic materials that will withstand evermore extreme conditions of temperatureand pressure, as well as being safe andeconomical.

the funding also includes a Doctoraltraining Partnership (DtP) to help createthe next generation of world-classmaterials scientists and metallurgicalengineers. ‘the UK is experiencing achronic shortage of materials scientistsdespite a clear industrial need,’ said

Dr Cathie Rae, who is coordinating theCambridge DtP. A total of 60 studentsacross the three universities will undertakeresearch of strategic value to Rolls-Royceand the gas turbine industry in general, as well as taught courses amounting to a year of training. ‘our goal is to equipscientists of the future with the skillsneeded to underpin industries as diverseas aeroengineering, nuclear power andconstruction.’

For more information, please contactDr Howard Stone ([email protected])or Dr Cathie Rae ([email protected]).

Strategic research partnership drivesmaterials science research and training Rolls-Royce and the Engineering and Physical Sciences ResearchCouncil (EPSRC) will work jointly with the Universities ofCambridge, Birmingham and Swansea in a new £50 millionstrategic partnership.

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Naked Scientist takes on materials sciencethe Rolls-Royce Strategic Partnership includes funds to recruit a new member to the award-winning naked Scientists team,whose weekly radio programmes and podcasts reach a worldwide audience of more than 20 million people per week. Working with naked Scientist Dr Chris Smith, the new team member’s focus will be to publicise materials science research as a means to improving the general perception of metallurgical engineering and to encourage more young people into science and engineering.

For more information, please contact Dr Chris Smith ([email protected]) or visit www.thenakedscientists.com/

Books and manuscripts of any period canhave unique and complicated personalhistories. ‘from the moment of inception,a text becomes a material object that canbe subjected to a whole host of lifeevents, which might encompass how it iscopied, edited, published, disseminated,reviewed, revised or preserved,’ explainedDr Jason Scott-Warren, Director of thenew Centre for material texts in thefaculty of english. ‘Whether the text is amedieval manuscript copied by monks, acommonplace book passed from oneowner to another, or a bestsellerconverted into a screenplay, each has anembodied history.’

the recently launched Centre willfoster teaching and research in the studyof material texts across Cambridge. it will offer intellectual and practicalsupport, as well as opportunities forcollaboration through sharing of ideasand expertise. ‘our aspiration is to draw in researchers working in differentdisciplines, different historical periods and different manifestations of text,’ said Dr Scott-Warren.

one aim of the Centre will be tocoordinate web custodianship ofdigitisation projects such as the recentlycompleted Scriptorium project (see page26), which provides rich and varied

resources for manuscript research andteaching.

‘the faculty has a strong track recordin bibliographical scholarship, manuscriptstudies and textual research of variouskinds,’ explained Professor Adrian Poole,head of the faculty of english. ‘theCentre will help us to coordinate andenhance this research, and to reach outto other disciplines, united by a commonfascination with the materiality of thesources we work with.’

For more information, please contactDr Jason Scott-Warren([email protected]).

Unlocking the history of the bookA new chapter in textual scholarship is beginning, thanks to the launch of the Centre forMaterial Texts.


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Cancer will affect one in three of usduring our lifetime and is a leading causeof death and disability worldwide. todaythough, there is a new sense of optimism,as scientific advances have led us to thepoint where an understanding of themolecular and cellular biology of canceris being translated into real benefits forpatients.

over the past 10 years, cancerresearch efforts within the University, theCambridge University hospitals nhSfoundation trust (Addenbrooke’s) and themany institutes and centres in Cambridgeand nearby have been drawing scienceand medicine closer together. helping toconnect this research community, avirtual Cambridge Cancer Centre waslaunched in 2006 to promote interactionsamong researchers and clinicians workingin diverse areas, as well as with biotechand pharmaceutical companies. thevirtual organisation promotes informationexchange between members, hostscross-disciplinary scientific meetings (seepage 35) and makes available pump-priming grants for new collaborativeresearch with potential clinicalapplication.

Creating the researchenvironmentClinical research must be nourished andrenewed from fundamental research.Across the University, cancer research isstrongly represented in manydepartments – from the biomedicalsciences to the physical sciences, andincreasingly embracing mathematics,engineering and computational biology.Research projects are investigating allaspects of cancer, whether it’s at the levelof DnA, cells or populations. Researchgoals include identifying newtherapeutics, imaging tumours, anddevising computational approaches thatanalyse vast amounts of data.

three major laboratories inCambridge have been created with a

focus oncancer research:the Cancer Research UKCambridge Research institute (CRi)/Li KaShing Centre, the hutchison/medicalResearch Council Research Centre, andpart of the Strangeways ResearchLaboratory. together, they provide space for almost 500 researchers, plusstate-of-the-art supporting facilities for technologies such as genomesequencing, molecular imaging,microscopy and computational biology.But more than this, the new laboratoriesare bridging the interface betweenscience and the clinic.

Translating research intopatient careSuccessfully applying the results ofresearch requires an excellent clinicalservice and clinical research environment.Cambridge is very much a cancer centrewhen it comes to strengths in clinical andhealthcare innovation. Cancer was one ofthree main themes when CambridgeUniversity health Partners, which includesthe Cambridge University hospitals nhSfoundation trust and the University, wasselected last year by the Department ofhealth as one of five Academic healthScience Centres in the UK. it was also theleading theme when an internationalpanel selected Cambridge as one of fiveBiomedical Research Centres funded bythe nhS in 2006.

intensive studies in experimentalmedicine are being built up incollaboration with major pharmaceuticalcompanies and academic researchers.multidisciplinary clinical teams for eachcancer type have been created thatinclude University and nhS staff workingclosely together, enabling research andclinical care to proceed side by side.

Catalysing great ideasnew ideas are likely to lie at theboundaries between disciplines or

between laboratory and clinic, and evenat the margins of conventional careerpaths and funding. At the CRi, forexample, many researchers are alsoclinicians, and oncologists work alongsidemathematicians, biochemists and cellbiologists. Across Cambridge, animportant part of the long-term vision isto stimulate training programmes toequip researchers to cross traditionalacademic boundaries.

Playing to scientific strengths, muchcurrent research is focusing on achievingearlier diagnosis and treatment in high-risk groups, discovering the determinantsof treatment resistance, and providingindividually tailored treatment(personalised medicine) based ongenomic information. By harnessing thecatalytic effect of the Cancer Centre onCambridge science, great opportunitieslie ahead in the development of powerfulnew approaches to diagnosing andtreating cancer.

CambridgeCancer Centre:the visionProfessor Sir Bruce Ponderdescribes the vision of aCambridge-wide initiative tolink world-class cancer researchto improved patient care.

For more information, please contactProfessor Sir Bruce Ponder([email protected]), the Li Ka Shing Professor of Oncology,Director of the Cancer Research UKCRI/Li Ka Shing Centre(www.cambridgecancer.org.uk/) andDirector of the Cambridge CancerCentre (www.cancer.cam.ac.uk/).

Professor Sir Bruce Ponder


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Professor Tony Kouzarides

For more information, pleasecontact Professor Tony Kouzarides([email protected]),the Royal Society Napier Professor,at the Wellcome Trust/CancerResearch UK Gurdon Institute(www.gurdon.cam.ac.uk/). Thisresearch was published in Nature(2009), 461, 819–822.

Professor Kouzarides has recentlyfounded ‘Vencer el Cancer’ (ConquerCancer), a cancer charity in Spainwhose goal is to raise funds fromthe public to fund cancer researchand drug discovery. The idea is toemulate Cancer Research UK in thefundraising strategies that havebeen so successful in the UK.

the basic functioning of our cells isgoverned by complex signallingpathways that relay what’s happeningaround and within cells to their controlcentre – the cell’s nucleus. the nucleusresponds by regulating which genes inour DnA are switched on and off. Whenthis fine-tuned regulation goes wrong,diseases such as cancer can result.

At the heart of this gene regulationare proteins called histones, aroundwhich DnA is wrapped rather like beadson a string, before being supercoiled intoa structure called chromatin. But histonesare not just a packing material. histonesalso act as beacons, guiding enzymes tospecific locations on the genome in orderto turn genes on and off. Professor tonyKouzarides’ research group at theWellcome trust/Cancer Research UKgurdon institute discovered in the 1990sthat this process is governed byenzymatic machinery that modifies thehistone proteins. many of the pathwaysthat lead to the modification of histonesare deregulated in cancer.

Professor Kouzarides’ latest discovery,in collaboration with Professor tonygreen’s group in the Department ofhaematology, has made a crucial linkbetween a faulty histone-modifyingenzyme and leukaemia.

New route to leukaemiathe research, funded by Cancer ResearchUK and published recently in Nature, wascarried out by Dr Andy Bannister and PhDstudent mark Dawson. they studied anenzyme known as Janus kinase 2 (JAK2),which functions as a signal transducer –

essentially, a component of the cell’ssignalling pathways that converts onetype of signal to another. faulty JAK2 hasbeen linked with leukaemia for a numberof years.

the breakthrough came when thescientists found an unknown signallingfunction of JAK2. Previously, JAK2 hadbeen thought to transduce signals onlywithin the main part of the cell, but theresearchers showed that it can enter thenucleus and modify histones. importantly,they discovered that the modificationnormally switches on a gene that causesleukaemia, and makes it remain onconstantly. the researchers haduncovered a direct mechanistic linkbetween a signal transducer, histonemodification and cancer.

Towards therapeuticsthe goal now is to continue theirongoing search for other enzymes thatmodify histone proteins (the group hasdiscovered several already). ProfessorKouzarides believes that these hold thekey to a future generation of cancertherapeutics. A University spin-out,Chroma therapeutics, was launched in2001 to exploit his research and that ofothers in the chromatin field, with theaim of harnessing the new understandingof chromatin biology to develop noveltherapeutics to prevent, diagnose andtreat cancer.

Leaps in understanding the basicmolecular genetics that control anddisrupt cell function are bringing a newgeneration of therapeutics closer. Just ashistone proteins act as beacons for

Beacons of life anddeath: chromatinand cancerA new generation ofcancer therapeuticsis on the horizonthanks to fresh light being shed on how genes are switched on and off.

DNA is coiled around histone proteins (shown here asblue beads) and supercoiled into fibres of chromatinbefore being condensed into chromosome structures

drawing signalling enzymes towardsDnA, they are also beacons for cancerresearchers intent on increasing thearsenal of anticancer therapeutics.

how likely we are to develop cancer isdetermined by our genes and our lifestyle.Likening this to a hand of cards, the risk ofcancer depends on whether we inheritgood cards or bad cards and also how weplay them (our lifestyle). Some genes carrya very high risk, which is why someindividuals have a particularly strong familyhistory of cancer. most of the time,however, cancer risk is determined by acombination of genes conferring a moremoderate risk; nevertheless, the overall riskcan be high (a bad hand) if there areenough of these genes.

At Strangeways Research Laboratory(SRL) in Cambridge, the research groups ofProfessor Doug easton, Dr Paul Pharoahand Dr Alison Dunning, supported withover £9 million of funding from CancerResearch UK, are working out the role ofnormal human genetic variation in cancerrisk – essentially, which hands of cards areworse than others.

The SEARCH beginsSeveral high-risk gene defects, such asmutations in BRCA1 and BRCA2 in breastcancer, have been identified throughfamily studies. Work in the 1990s at SRL byProfessor Sir Bruce Ponder, who is nowDirector of the Cancer Research UKCambridge Research institute (CRi), andProfessor easton helped track down thesetwo genes. however, among the generalpopulation, these defects are usually rare,and most cancers are the result ofinheriting several more-common genemutations. for breast cancer, these more-common gene defects account for asmuch as 80% of inherited risk, accordingto findings at SRL.

‘the trouble is, the individual effects of common genetic variants are small andto get reliable evidence about specificvariants you need to sample largenumbers of people,’ explained Professoreaston, Director of the Cancer Research UKgenetic epidemiology group. Key tofinding these mutations has been theassembly at SRL of one of the largestpopulation studies of cancer everconducted, along with the uniqueexpertise that the team has gatheredtogether in cancer epidemiology,biostatistics, large-scale genetic analysisand public health medicine.

this work was started in 1996 byProfessor Ponder and Professor nicholasDay, who recruited Dr Paul Pharoah as aClinical fellow to enrol patients with breast cancer. the enrolment was later extended to include patients with ovarian, colorectal or uterine cancer, aswell as participants with no history ofcancer. the project, now called SeARCh,was further extended five years ago toinclude bladder, brain, kidney,oesophageal and pancreatic cancers, as well as melanoma and non-hodgkin’slymphoma. ‘our early investment in well-curated and very large study sets,with blood samples, pathology review and clinical data, has been absolutelycrucial as it has provided the statisticalpower for reliable conclusions aboutcommon genetic variants,’ explainedProfessor Ponder. today, SeARCh numbers nearly 27,000 cases and normalcontrols from the east Anglia region,providing a remarkable and growingresource: by 2013, the hope is that this will have expanded to 35,000.


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Cancer:what’s onthe cards?

Scientists at StrangewaysResearch Laboratory areleading the search for the‘genetic cards’ thatdetermine an individual’srisk of cancer.

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BCAC: Breast Cancer AssociationConsortium

BOADICEA: Breast and ovarianAnalysis of Disease incidence andCarrier estimation Algorithm

CIMBA: Consortium ofinvestigators of modifiers ofBRCA1/2

EMBRACE: epidemiological Studyof familial Breast Cancer

OCAC: ovarian Cancer AssociationConsortium

PRACTICAL: Prostate CancerAssociation group to investigateCancer Associated Alterations inthe genome

ProtecT: Prostate testing forCancer and treatment

SEARCH: Studies of epidemiologyand Risk factors in Cancer heredity


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Going global‘SeARCh has shown that the size of thedataset is really important for assessingthe impact of common genetic variantsaccurately,’ explained Dr Pharoah, wholeads a research group at SRL from theDepartment of oncology. ‘the logicalnext step was to combine data fromSeARCh with other studies that hadbeen happening worldwide.’

Cambridge now coordinates fiveinternational consortia of study groups:two consortia studying breast cancer,one each studying ovarian and prostatecancers, and a newly formed consortiumto examine genetic differencesunderlying adverse side-effects fromcancer radiotherapy (see right panel).from SRL, the consortia pull in not justSeARCh but also other studies such asProtect, a prostate cancer study led byCambridge’s Professor of Surgicaloncology, David neal, together withProfessor freddie hamdy in oxford andProfessor Jenny Donovan in Bristol; andthe familial breast cancer studyemBRACe, led by Professor easton. thescale of the endeavour is unprecedentedin population studies, and the europeanUnion has recently awarded €12 millionto coordinate these large-scale geneticstudies in breast, ovarian and prostatecancers.

‘Apart from increasing the reliabilityof the data,’ said Professor easton, ‘theinternational consortia afford theopportunity to study populations fromdifferent parts of the world wheredifferent genetic and lifestyle factors are operating.’

Gene huntingimprovements in technology that wouldhave been hard to imagine whenSeARCh began are now being used toanalyse the data, demonstrating theenormous foresight in setting up such a resource a decade ago.

‘We know that there are about 10 million variants in the genome, butchoosing the right ones to test forassociation with cancer has in the pastowed a great deal to chance, with theresult that very few positive associationswere identified,’ said Dr Dunning, wholeads the high-throughput laboratoryteam within the SRL. ‘now, though,thanks both to the ability to carry outgenome-wide scans and the samplescollected through the internationalconsortia, we can pinpoint the variantsthat are definitively linked to the risk ofcancer.’

A full genome scan for breast cancer,the first of its kind, was completed in

2007 by the researchers and published inNature. full genome scans of prostateand ovarian cancers have since followedin Nature Genetics. in the latest scan,published in october 2009, the genomesof 38,000 men with and without prostatecancer were analysed for over 43,000single differences in DnA (called singlenucleotide polymorphisms or SnPs),revealing multiple new cancer generegions.

to date, 13 predisposing generegions have been identified for breastcancer, five for ovarian cancer and 27 forprostate cancer, findings that havesignificant implications for targetedscreening and prevention in the future.Since most of these newly discoveredregions contain genes that had notpreviously been considered in cancer,they will also provide new insights intothe biology of the disease. going forward,Professor Ponder’s group at the CRi isdeveloping phenotypic assays as a read-out of cancer risk, studying how riskgenes exert their function and searchingfor molecular markers for future studies ofearly diagnosis and prevention. Professorfiona Watt at the Wellcome trust Centrefor Stem Cell Research is also studyingthe biological effects caused by thesegene defects to understand what goeswrong in cancer.

Professor neal, in the Department ofoncology and CRi, has been investigatingwhether a protein made by one of thenewly discovered prostate loci can beused as a screening and diagnosticmarker in prostate cancer since it can be measured in serum and urine. earlyresults suggest not only loss of theprotein in prostate cancer, but also adecrease in men who possess the high-risk form of the gene but who have notyet developed prostate cancer.

Translational toolsBut what does this all mean tounderstanding our own risk? for breastand ovarian cancer, Dr Antonis Antoniouand Professor easton have developed acomputer model named BoADiCeA thatcan predict an individual’s risk of thesecancers. the tool is already being usedby genetic counsellors to identify high-risk individuals, referring them forcounselling and regular screening ifappropriate, and providing advice aboutways to lower their risk. As new datacome to light from the genome scans,BoADiCeA will continually be improved,providing increasingly accurateinformation to individuals wishing toknow the hand of genetic cards thatthey’ve been dealt.

For more information, please contact Professor Doug Easton([email protected]), Dr PaulPharoah ([email protected])and Dr Alison Dunning([email protected]) at theStrangeways Research Laboratory(www.srl.cam.ac.uk/) or visit the SEARCHwebsite (www.srl.cam.ac.uk/search/Homepage.htm).

Dr Alison Dunning, Professor Doug Easton and

Dr Paul Pharoah (left to right)

Worldwide consortialed by StrangewaysResearch Laboratory

BCAC: 100,000 breast cancer casesand controls; 55 study groups

CIMBA: 25,000 breast cancer casesand controls; 42 study groups

OCAC: 30,000 ovarian cancer casesand controls; 34 study groups

PRACTICAL: 25,000 prostate cancercases and controls; 27 study groups

Radiogenomics Consortium: newlyformed; 23 study groups


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Cambridge scientistsare asking what rolestem cells play in howcancer develops,spreads and relapses.

Stem cells (shown here in red) are responsible for the maintenance and regeneration of all the cells in a tissue

most tissues in the human body aremaintained by stem cells – master buildersand repairers that replenish different typesof cells when needed. the uniqueproperties of stem cells are of greatinterest to scientists investigating thepossibility of regenerating and repairinghuman tissues. But stem cells have alsocome under close scrutiny in relation tocancer, since the ability to self-renew is acharacteristic of tumours. Research intocancer stem cells is offering new insightinto how cancer cells grow and how sometumours relapse even following powerfultherapy.

Cambridge has a very active stem cellcommunity, recognised as a centre ofexcellence by the Wellcome trust (Wt)and the medical Research Council (mRC). A major research theme within thiscommunity is the Cancer Stem CellProgramme at the mRC Centre for StemCell Biology and Regenerative medicine.Professor fiona Watt, who directs theProgramme, explained why cancer stemcells are so interesting: ‘Pathologists haveknown for centuries that within a singletumour there can be cells that differ inmaturity. it is now becoming clear that thisheterogeneity reflects, at least in part, theexistence of cancer stem cells and theiroffspring, and that these cells play a crucialrole in the life history of cancer. eradicatingthese master builders would strike at theheart of the tumour.’

Cancer stem cellsthe Cancer Stem Cell Programme bringstogether clinicians and scientists withexpertise in haematological, epithelial andbrain cancers.

one of the best-studied adult stem cellsystems is the process by which the many

different cell types found in blood areconstantly replenished. Professor tonygreen and Dr Brian huntly in theDepartment of haematology are usingthis process as a paradigm forunderstanding leukaemias: ‘We areespecially interested in the molecularrewiring that underlies the change from anormal cell to a cancerous stem cell,’explained Professor green. A recentsuccess has been the discovery of a newmolecular mechanism for leukaemia (see page 9).

to identify cancer stem cells and theircomplex interactions, researchersfrequently develop biological models ofcancer. Dr Stephen goldie in ProfessorWatt’s lab, in collaboration with cliniciansat Cambridge University hospitals nhSfoundation trust, is investigating cancerstem cells in human head and necktumours by creating models thatrecapitulate the original human tumour.‘interactions between the tumour and itsenvironment are being tracked by state-of-the-art imaging technology toestablish which cells are responsible formaking the tumours and what can bedone to make the tumour shrink andstop spreading,’ explained Dr goldie.

Scientists from the Centre for BrainRepair in the Department of Clinicalneurosciences and the Wt Centre forStem Cell Research are investigating stemcells in brain cancer. ‘Brain canceraccounts for a disproportionate numberof cancer deaths and new treatments areurgently required,’ explained Dr ColinWatts, Consultant neurosurgeon, fromthe Centre for Brain Repair. ‘thesetumours contain stem-like cells that areresistant to current treatments. Work inthe Centre aims to understand the

mechanisms underlying this resistanceand to develop ways of killing these cells.’

Driving new treatmentsthe current thinking is that cancer stemcells constitute a minority of the cellswithin a tumour and, although they arecapable of dividing continually, they maydo so relatively slowly. most therapies aretargeted towards rapidly dividing cells,which might kill the bulk of the tumourbut not the cancer stem cells.Understanding more about cancer stemcells is therefore crucial, as Professor Wattexplained: ‘future treatments that arespecific for cancer stem cells will not onlybe more effective in treating the disease,but will also incur less collateral damageto the patient’s normal tissues.’

Understanding howcancer cells grow

Professor Fiona Watt

For more information, please contact Professor Fiona Watt([email protected]), theHerchel Smith Professor of MedicalGenetics, at the WT Centre for StemCell Research (www.cscr.cam.ac.uk/) and the Cancer Research UKCambridge Research Institute/Li Ka Shing Centre(www.cambridgecancer.org.uk/).

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the advent of new technologies hasenabled researchers to interrogate humangenomes at unprecedented resolution.these technologies have led to a wealth ofgenomic information that has the capacityto shed new light on complex diseases,but they also generate far too much datato interpret by eye. Consequently, novelcomputational and statistical techniqueshave evolved to extract meaningfulpatterns from the data (‘data mining’) andto integrate this with other types ofbiological information in an attempt tomake sense of what it all means.

in Cambridge, a collaboration betweenthe Computational Biology group at theCancer Research UK Cambridge Researchinstitute (CRi), led by Professor Simontavaré (also at the Department of Appliedmathematics and theoretical Physics), andProfessor Carlos Caldas and Dr JamesBrenton (who are both at the CRi and theDepartment of oncology) seeks to do justthis, demonstrating the power ofcombining expertise in statistics,computational and experimental biology,and clinical medicine to understand cancer.

METABRICBreast cancer, like other malignancies, isdriven by the progressive acquisition ofkey genetic alterations that confer growthadvantages on the cell. most of theacquired aberrations are merely‘passenger’ events that do not influencecancer progression, whereas the ‘driver’events are critical mediators of disease. it isthese ‘driver’ events and the effects theyelicit that researchers seek to identify, theproblem being akin to searching for aneedle in a haystack.

metABRiC (molecular taxonomy ofBreast Cancer international Consortium) is

an Anglo-Canadian effort aimed at findingthe ‘needles’, and is funded by CancerResearch UK and the British ColumbiaCancer foundation. given the substantialmolecular heterogeneity among breastcancer patients, metABRiC seeks tointerrogate the genomic andtranscriptional landscape of over 2,000clinically annotated breast tumourspecimens to generate a robust moleculardescription of the disease.

each sample is examined fordifferences in gene expression levels, aswell as for alterations in the number ofcopies of each gene, by combiningmeasurements from nearly two millionprobes that query the genome atsequential positions. Add to this a varietyof other data types and five years ofclinical history, and you wonder how thesheer volume of data can be processed, let alone interpreted. in fact, a majorchallenge with such high-dimensionaldatasets is the identification of truedifferences amid inherent backgroundnoise. how can one see the forest for thetrees in the cancer genome landscape?

Seeing the forest for the treesDr Christina Curtis in the ComputationalBiology group is leading the analysis ofmassively parallel technologies usingcomputational and statistical methods tomake sense of this vast data deluge. muchof her research relies on high-performancecomputing to process these and otherlarge datasets. fortunately, the CRi housesa computer cluster with nearly 500 coresand multiple high-memory nodes that willexpand to meet the growing need forcomputational capacity.

Using novel analytical approaches fordata integration and mining, Dr Curtis and

her team have defined additional subtypesof breast cancer based on their uniquemolecular characteristics, providing freshinsight into mechanisms of breast cancertumourigenesis. future work will relatethese molecular profiles to specific clinicalphenotypes and identify markers thatimprove the classification of breast cancer.importantly, the techniques employed formetABRiC are sufficiently general to beapplied to a variety of other cancerdatasets.

Computational biology is providingthe means to navigate through large-scale,multi-dimensional datasets. in doing so, itcan help to build a holistic, systems-levelperspective on cancer that will shapefuture clinical practice.


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Searching for patterns in cancer genomes amid vast amounts of information

Data mining the complexcancer landscape

Computational biology is helping scientists tonavigate through the data deluge generated

from the analysis of cancer genomes.

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Professor Simon Tavaré, Dr James Brenton andProfessor Carlos Caldas

(left to right)

For more information, please contactProfessor Simon Tavaré([email protected]) and Dr ChristinaCurtis ([email protected]) at the CancerResearch UK Cambridge ResearchInstitute/Li Ka Shing Centre(www.cambridgecancer.org.uk/).


Discovering and evaluating anticancerdrugs is a billion dollar business. mucheffort is put into the discovery of noveldrug targets and then elegant chemistryapproaches are used to design andsynthesise new therapeutics. ‘With theincreasing biological understanding ofcancer, an increasing repertoire ofpotential targets has been identified,’explained Professor Duncan Jodrell, at theCancer Research UK Cambridge Researchinstitute (CRi). ‘But, in the past, time andmoney have been wasted performinglarge-scale clinical trials on compoundsthat end up not having a significantimpact on cancer. With many morepotential drugs, we need to avoid thishappening in the future’. therefore, a majorquestion is which drugs should beprogressed to clinical trials?

Professor Jodrell and Dr David tuveson,also at the CRi, believe that the answer liesin re-designing the way that preclinicalstudies are performed and in developingmore-relevant animal models of thehuman disease. essentially, smart drugsdeserve smart evaluation. ‘thedevelopment of anticancer drugs istherefore likely to have the highest impactwhen performed at centres that are world-leading in preclinical cancer models, noveltherapeutics, molecular imaging and‘science-led’ clinical application of novel therapies in patients,’ explained Dr tuveson. ‘All of these components arecoming together at the CRi andlaboratories close by.’

GEMs of discoveryfor many years, mouse models havebeen an invaluable resource tounderstand the mechanisms thatunderpin cancer in human patients.these models have become increasinglysophisticated, starting with xenograftmodels, in which part of a tumourremoved from a patient is transplantedinto mice, through to the latestgenetically modified mouse (gem)models, which carry the mutations thathave been associated with particularhuman cancers.

‘one bottleneck for bringing newtherapies into the clinic is the extent towhich preclinical testing quickly andaccurately predicts how well a drug willperform once it enters clinical trials inpatients,’ explained Dr tuveson, who leadsthe tumour modelling and experimentalmedicine group. ‘our goal is to improvethe ability to discriminate between drugsthat will have significant patient benefitsand those that won’t.’

Dr tuveson’s particular focus has beenon pancreatic cancer and melanoma –two of the most difficult cancers to treat.Despite the fact that we now knowwhich gene is predominantly responsiblefor each of these types of cancers,patients have a poor prognosis as fewtreatments are available and manytumours do not respond to them.

Recently, his group discovered a newmechanism that might explain whypancreatic cancer is often resistant to

Given that it costs anestimated $1 billion to bringa new cancer drug tomarket, can better decisionsbe made about which drugsto test in the clinic?

Smarttesting for

smart drugs

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Which anticancer drugs should be progressed to clinical trials?


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Professor Duncan Jodrell (left)and Dr David Tuveson

For more information, please contact Dr David Tuveson([email protected]) andProfessor Duncan Jodrell([email protected]) at theCancer Research UK CambridgeResearch Institute/Li Ka Shing Centre(www.cambridgecancer.org.uk/).

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gemcitabine, a commonly usedanticancer treatment. Working withcolleagues at Cambridge Universityhospitals nhS foundation trust(Addenbrooke’s) and laboratories in theUSA and europe, the scientists found thatresistance to chemotherapy is the resultof the pancreatic tumours having a poornetwork of blood vessels, which makes itharder for drugs to reach the tumour. thisresult, published a few months ago inScience, may also explain why anticancerdrugs targeted at blood vessels (whichsome tumours have in abundance) don’twork for pancreatic cancer.

‘Working out why some tumoursshow a disappointing response tochemotherapeutic drugs has enabled usto look at what can be done to overcomethis therapeutic intractability,’ said Dr tuveson. ‘if the door has been closedto therapy, perhaps we can find a way ofreopening it?’ early studies have shownthat a compound called iPi-926, createdby infinity Pharmaceuticals, reduces theamount of tissue surrounding thetumour, allowing greater access forgemcitabine.

Dr tuveson is also working withcolleagues at the Wellcome trust Sangerinstitute to identify genes and pathwaysthat influence cancer development –information that will be used to developnew models that mimic human cancers.the proximity in Cambridge of severaldrug development programmes – suchas the Cambridge molecular therapeuticsProgramme at the hutchison/medicalResearch Council (mRC) Research Centre(see page 18) and groups within theDepartments of Chemistry andBiochemistry – will offer broad access tonovel therapeutic classes for this work.

Entering a new phase‘Although the results are extremelypromising,’ said Dr tuveson, ‘these are earlydays and we need to show that thisapproach is safe to use in humans beforewe can consider adding the newcompound to cancer treatments.’ to dothis, Dr tuveson is working with ProfessorJodrell, who leads the Cancer Research UKPharmacology and Drug Developmentgroup at the CRi and a closely associatedearly Phase trials team based inAddenbrooke’s hospital.

Professor Jodrell is interested in whatanticancer drugs do to the body(pharmacodynamics) and how the bodyhandles the drug (pharmacokinetics).‘these are important determinants of successful therapy since themeasurements provide information onwhether the drug is hitting the righttarget. We also learn how long the drughangs around to do this before it’smetabolised or eliminated.’

An oncology clinic for pancreaticcancer patients is being developed atAddenbrooke’s hospital and early phaseclinical trials are performed in theWellcome trust Clinical Research facilityon the same campus. this allows thepreclinical studies initiated in CRilaboratories to be translated into clinicalbenefits for patients. trials will be availablefor patients with both early and advanceddisease. ‘We will be looking for biomarkersthat can identify which tumours willrespond to a particular treatment, as wellas markers that demonstrate early that thetreatment is working,’ explained ProfessorJodrell. ‘the goal is to identify whichpatients will benefit from drugs, and toget more information at an earlier stageto inform those ‘go/no go’ decisions for

progressing a drug through to later-phaseclinical trials.’ for both the preclinical andclinical studies, novel imaging techniquesdevised by Professor Kevin Brindle (seepage 16) and Professor John griffiths atthe CRi may provide instantaneousassessment of response to treatment. inpatients, these non-invasive imaging toolswill hopefully maximise the informationaccrued, yet avoid the discomfort forpatients of undergoing serial biopsies toobtain tumour tissue.

information from the preclinicalmodels of pancreatic disease developedby Dr tuveson will soon be integratedinto clinical trials. A clinical trial protocolwill commence in Cambridge in early2010 to test novel combinations ofgemcitabine and other drugs.Collaboration with Dr Adrian mander,leader of the mRC Biostatistics Unit hubin trials methodology Research inCambridge, is providing statisticalapproaches to maximise the informationderived from the trials.

Anticancer cocktailsthe unique mirroring arrangementbetween preclinical models and clinicaltrials that is being created in Cambridgeholds great promise for moving towardsindividualised therapy for cancer patients.novel and established drugs can betested quickly and effectively to work outthe appropriate combination that willovercome lack of response to treatment.‘it’s now possible to imagine the day,’ saidProfessor Jodrell, ‘when each patient istreated with a personalised cocktail ofdrugs that takes account of the specificattributes of their cancer.’

Recent research shows that the anticancer drug gemcitabine (stained green) is unable to reach pancreatic tumours (stained blue)

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increasing the speed and sensitivity ofdetecting how tumour cells areresponding to treatment is something ofa holy grail in the field of oncology.treatment response is still largelyassessed by looking for a reduction intumour size using magnetic resonanceimaging (mRi) or X-ray computedtomography. But many tumours may takeweeks or even months to show evidenceof regression and, in some cases, may notregress at all despite a positive responseto treatment. how can an earlierindication of response be achieved sothat clinicians can select the besttreatment for an individual patient?

new techniques are being pioneeredin Cambridge to ‘see’ tumour cells asnever before. Research in Professor KevinBrindle’s laboratory is developing a varietyof clinically applicable, non-invasive,imaging techniques that measure tumourcells ‘eating, breathing and dying’.

Spin doctorone approach under investigation by theBrindle lab is based on mRi. Although thistechnique has been around since the1970s, the new imaging method has acrucial difference – instead of detectingthe distribution and properties of waterprotons in tissue, which conventional mRidoes, the new approach detects withmuch greater sensitivity than ever beforethe small molecules in tissues that arefundamental to their biochemistry. theseare the carbon-based metabolitesinvolved in producing energy and inmaking the constituents of the cell; achange in how these metabolites arebeing used can signal that an effectivetherapy is starting to kill the cells.

the problem with carbon-basedmolecules is that they are present in tiny

amounts compared with the protons intissue water, making them hard to detectand almost impossible to image at highresolution. to overcome this, the Brindlegroup has been collaborating with gehealthcare to develop a technique thatincreases mRi sensitivity by more than10,000 times.

to achieve such a dramatic increasein sensitivity, the scientists have turned tonuclear spin hyperpolarisation. Beforeintravenous injection, a molecule labelledwith an mR isotope of carbon ishyperpolarised so that a large proportionof the carbon nuclear spins line up withthe magnetic field, as opposed to only afew in a million in a conventional mRexperiment. the resulting gain insensitivity means that the researchers canwatch how the hyperpolarised carbon ismetabolised by tumours, using this as aread-out for living and dying cells. Datapublished recently have shown how wellthis technique works for monitoringtreatment response, and the first clinicaltrials are planned to start in 2010.

Personalising medicineDifferent tumours are likely to requiredifferent imaging methods. With recentfunding from the Leukaemia andLymphoma Society, a new study has justbegun in which several of the imagingmethods under development in theBrindle group are being validated inmodels of lymphoma (see oppositepage), so that the best reagents andprotocols can be selected for futureclinical trials.

improved imaging methods are notonly useful in the clinic, but will also beinvaluable for early stage clinical trials ofnew drugs, where the need to establishwhether new treatments are working is

particularly acute. Professor Brindle isworking with Professor Duncan Jodrelland Dr David tuveson at the CancerResearch UK Cambridge Researchinstitute to develop imaging methodsthat allow treatment responses inindividual patients to be measuredimmediately (see page 14). Becausepatients with similar tumour types canshow markedly different responses to thesame therapy, imaging will be animportant component of the armoury of‘personalised medicine’, enabling themost effective treatment to be tailored tospecific patients.

For more information, please contactProfessor Kevin Brindle([email protected]) at theDepartment of Biochemistry(www.bioc.cam.ac.uk/) and the CancerResearch UK Cambridge ResearchInstitute/Li Ka Shing Centre(www.cambridgecancer.org.uk/). Thisresearch was published in Proceedingsof the National Academy of Sciences(2009) 106, 19801–19806 and wasfunded principally by Cancer ResearchUK, with material support from GEHealthcare.

Professor Kevin Brindle

Watching cancer cells eat,breathe and dieCancer cells can now be viewed as never before, thanks to cutting-edge imaging tools beingdeveloped in Cambridge.

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Visualising treatment response: lymphomaresponding to treatment, imaged using

hyperpolarised carbon (red signal indicatesgreater response)


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Visualisingchromosometranslocations:

nuclei of lymphomacells (blue) in whichchromosome 2 lights

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red; a yellow signalindicates thepresence of atranslocation

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Lymphoma is an umbrella term thatdescribes cancer of the white blood cells ofthe lymphatic system, which normally actsto protect the body against infection. inlymphoma, malignant changes in a whiteblood cell causes it to divide abnormallyand out of control; not only are these cellsunable to protect the body againstinfection, and in fact interfere with thegrowth of healthy cells, but they also buildup, often in lymph nodes, as tumours.

Lymphoma accounts for more than9,000 new cancer cases diagnosed eachyear in the UK alone and the incidence isrising by about 4% per year. Some of thesecases appear to result following viralinfections, immunodeficiency orautoimmunity, but for the most part wedon’t know what causes the geneticalterations underlying the different subtypesof lymphoma, of which over 30 are nowknown. however, progress is being made inunderstanding what effect the geneticalteration has on the cell in which it occurs.

Dr Suzanne turner leads a group in theDepartment of Pathology who areinterested in a subtype of lymphoma that,although rare, has become a paradigm for understanding the growth anddevelopment of lymphomas(lymphomagenesis) because of its well-defined genetic alteration.

the many different subtypes oflymphoma have alterations that range fromsingle mutations, through loss and gain inregions of genetic material, to large-scalechromosomal changes. the cancer thatinterests Dr turner, anaplastic large celllymphoma (ALCL), falls into this lastcategory because it results when sections ofgenetic material from two chromosomesare essentially ‘cut and pasted’ in the wrongplace.

Dr Suzanne TurnerFor more information, please contactDr Suzanne Turner ([email protected])at the Division of MolecularHistopathology in the Department ofPathology (www.path.cam.ac.uk/). Dr Turner is a Leukaemia ResearchBennett Fellow and is also funded bythe Kay Kendal Leukaemia Fund andCancer Research UK.

Cut-and-pastecancer:lymphoma’sgenetic blueprintResearchers in the Department of Pathology have established precisely how the ‘cutting andpasting’ of genetic material from one chromosome to another results in cancer.

Genesis of a lymphomaAlthough relatively rare in adults, ALCLaccounts for 1 in 10 cases of alllymphomas in children. the mostcommon type of ALCL is caused by theswapping of genetic material betweenchromosomes 2 and 5. Rather like thejoining together of parts of two differentsentences, swapping segments ofchromosomes can sometimes result innonsense. But in some cases, the twoparts produce an intelligible outcome,albeit with a different meaning. this iswhat happens in ALCL: the alteredgenetic code, which juxtaposes the genefor nucleophosmin (nPm) onchromosome 5 with the gene foranaplastic lymphoma kinase (ALK) onchromosome 2, generates a new geneproduct (nPm-ALK) at the fusion pointbetween the two chromosomes.Although only portions of the two genesremain, together they create a newprotein with altered functions.

Dr turner’s group was one of the firstresearch groups in the world todemonstrate that nPm-ALK can causecancer. they discovered that the errantprotein sets off a cascade of events thatconfers survival and growth properties onthe cells in which it is expressed. the cellsproliferate uncontrollably and alymphoma is born.

A model systemDr turner’s group has developed modelsystems to investigate both the specificcell type in which the translocation anddisease originate and whether the normalfunctions of the immune systemcontribute to the disease process.Potential new drugs and drugcombinations, particularly those that

inhibit the nPm-ALK protein, are beingtested with the long-term aim of takingthese into the clinic. A collaboration withDr Amos Burke, Consultant oncologistwithin the Department of Paediatrichaematology and oncology at CambridgeUniversity hospitals nhS foundation trust,provides an important clinical perspectiveon the work. And new imaging methodsdeveloped by Professor Kevin Brindle in theCambridge Research institute (seeopposite page) are being used to detecttreatment response at an early stage.

for ALCL, the long-term goal is todevelop a way of inhibiting nPm-ALK andthe catastrophic malignant effects that itinitiates within the white blood cell inwhich it occurs. But these studies will alsocomplete a story – one that explains theway in which lymphoma can be set inmotion… and be stopped in its tracks.


how do different forms of cancer arise?Which individuals are most likely todevelop cancer? Why is cancer so difficultto treat? the hutchison/medical ResearchCouncil (mRC) Research Centre not onlyaddresses these questions through world-class fundamental research, but is alsoincreasingly recognised for translating thisinformation into improved diagnosis.

Integrating science andmedicinethe hutchison/mRC Research Centre wasestablished in 2001 and is jointly directedby Professor Ashok venkitaraman, ProfessorRon Laskey and Professor Sir Bruce Ponder.it occupies a unique niche within thecancer research community in Cambridgebecause it houses three integratedcomponents that bring together scientistsand clinical staff working towards commongoals. the mRC Cancer Cell Unit andlaboratories of the University’s Departmentof oncology are carrying out fundamentalresearch on the mechanisms that regulatethe division and fate of cancer cells, andare using this information to develop new tools for the early diagnosis of cancers (see opposite). the thirdcomponent is the Cambridge moleculartherapeutics Programme, which seeks to create innovative new platforms to make the next generation of cancer drugs (see opposite).

A multidisciplinary approachCancer research today involves a variety ofapproaches – from chemistry and imaging,to mathematical modelling and cellbiology, to clinical investigations and trials.the hutchison/mRC Research Centreprovides an excellent example of the rapidand substantive progress that can beachieved through a multidisciplinary andcollaborative approach.

many groups have strong links toresearchers in other UniversityDepartments such as Chemistry,Biochemistry, and Applied mathematicsand theoretical Physics. Bringing thesedifferent perspectives to the field of cancerresearch has had a major impact on ourunderstanding of the disease bycontributing new insights into problemsas diverse as cell division, proteinbehaviour and drug discovery.

this integrated, multidisciplinaryapproach to research also places thehutchison/mRC Research Centre firmly atthe heart of the Cambridge Cancer Centre,whose overall aim is to harnessCambridge’s wider strengths infundamental and applied sciences toimprove clinical outcomes for cancerpatients. As part of this initiative, thehutchison/mRC Research Centre willcontinue to build on its reputation foridentifying major clinical problems in thecancer field, addressing these problemsusing fundamental research, andtranslating the solutions into diagnostictools and treatments that improve humanhealth.

Hutchison/MRC Research Centre…where fundamental research is pioneering innovativeapproaches to cancer diagnosis and treatment.

Professor Ashok Venkitaraman

For more information, please visitwww.hutchison-mrc.cam.ac.uk/

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A major goal in public health is to detectcancer, or pre-cancerous changes, at anearly stage using methods that areeffective and practical enough to roll outto gP surgeries, medical screeninglaboratories and developing countries.

‘for cancer of the oesophagus,’explained Dr Rebecca fitzgerald, ‘mostpatients present with symptoms late on,when they are having trouble swallowing.By then, the chance of surviving five yearsafter therapy is only 20%, and yet the firstsigns of disease in these patients are oftenvisible 10–20 years beforehand.’

‘Screening for cervical cancer using thesmear test is a prime example of thesuccess of early detection programmes,’added Dr nick Coleman, ‘but cervicalchanges are subtle and a high degree oftraining is needed to recognise them.What’s needed is an effective way of automating screening.’

Professor Ron Laskey and Dr Colemanhave discovered a biomarker that enablesscreening for differences between normaland diseased cells. normal cells don’texpress mini chromosome maintenance(mCm) proteins, whereas cancerous andpre-cancerous cells express them inabundance. Screening for the presence ofmCm proteins in cervical smears cansubstantially improve early diagnosis. thetechnology has been licensed to Becton,Dickinson and Company, which is runninglarge-scale trials for cervical cancerscreening. meanwhile, the researchers arenow investigating the wider application ofthis tool: in colorectal cancer, incollaboration with mr Richard miller,Consultant Colorectal Surgeon in theDepartment of Surgery, in lung cancer andin anal cancer.

mCm proteins are also being used by Dr fitzgerald to detect pre-cancerous

changes in the oesophagus. Cancer of theoesophagus kills about 7,000 people eachyear in the UK, and the figure is increasing.two-thirds of cases develop through arecognisable pre-cancerous stage calledBarrett’s oesophagus and Dr fitzgerald hasdeveloped a means of detecting thiswithout endoscopy. A sponge on a stringis swallowed and is then gently withdrawnup the oesophagus, bringing with itsamples of the lining cells to be examinedfor evidence of biomarkers. following thesuccess of a pilot study of 500 patientswith a history of heartburn (associatedwith the development of Barrett’soesophagus), a much larger study is beingplanned to see just how accurate the testis in comparison with endoscopy.

testing positive to early detection tests will define much smaller groups ofindividuals who can then be offeredspecialist investigation and treatment at avery early stage of the disease, when thechances of full recovery are high.

For more information, please contact Dr Rebecca Fitzgerald([email protected]) or Dr Nick Coleman ([email protected]).

Improving cancer diagnosisMost common cancers are difficult to treat successfully once thecancer has spread. Scientists at the MRC Cancer Cell Unit in theHutchison/MRC Research Centre have identified improvedmethods to detect cancer early.

the discovery and clinical developmentof new medicines against humandiseases such as cancer is long, expensiveand inefficient. A major problem is thatfewer than 10% of the proteins encodedin the human genome have successfullybeen ‘drugged’ using conventionalmethods, making it difficult to targetthose linked with cancer. A second is thatthe failure rate during early clinicaldevelopment of new anticancer drugs isunacceptably high, largely due to poorunderstanding of their effects. the CmtPharnesses the strengths of Cambridgeacademic sciences to address these keychallenges, bringing together expertise inchemistry, structural biology, physics andengineering (led by Professors Chris Abell,tom Blundell and mike Payne) with thebiomedical research in the hutchison/

mRC Research Centre led by ProfessorAshok venkitaraman.

new approaches to widen therepertoire of ‘druggable’ targets start withthe development of novel assay platformsto identify the hard-to-find targets thatcharacterise different forms of cancer. Aplatform of innovative screening methodsis then used to discover chemical ‘leads’that can be used against them. theseinclude fragment-based methods, wheresmall fragments (rather than completedrug molecules) are soaked into crystalsof the target protein to identify the siteand nature of the binding interaction, andthis information is used in the design andsynthesis of the next generation ofinhibitors. Another approach involvesnovel ‘libraries’ of drug-like chemicals,which are screened for activity against

target proteins by biophysical assays, cell-based assays and in silico screens, and elaborated further using structuredetermination.

the second major strand of work inthe CmtP is to accelerate the early clinicaldevelopment of new anticancer drugsthrough improved understanding of theireffects on normal and cancer cells.Several new approaches are being taken,including the establishment of laboratorymodels that more accurately predict theeffects of drugs on human cancers, andmethods to screen for biomarkers thatdetermine which patients are most likelyto benefit from the drugs. this work hasalready led to the design of new types ofclinical trials that more effectively matchthe right drugs to the right cancer patients.

early success in developing these newapproaches has secured over £6 million infunding for the CmtP from sponsorsincluding the mRC and the Wellcometrust.

For more information about the CMTP,please visit www.cmtp.cam.ac.uk/ orcontact Professor Ashok Venkitaraman([email protected]), the Ursula Zoellner Professor of CancerResearch.

New approaches to cancerdrug discoveryThe Cambridge Molecular Therapeutics Programme (CMTP) isdeveloping innovative strategies to widen the repertoire of‘druggable’ cancer targets and accelerate the clinicaldevelopment of new medicines.


KnoWLeDge tRAnSfeR

A combination of aquatic ecology and chemical engineeringhas resulted in a novel means of combating an invasion of zebramussels into underground water mains. this non-native speciesoriginates from central Asia and has become one of the world’smost significant environmental pests. in the UK, zebra musselsgrowing at high density cause problems when they occlude rawwater mains that feed water-treatment works, water-coolingsystems in power plants and water supplies for drinking.

Dr David Aldridge, from the Department of zoology, and Dr geoff moggridge, from the Department of Chemicalengineering and Biotechnology, have invented anenvironmentally sound control method called the BioBullet,now being manufactured by their spin-out company BioBullets Ltd.

the fat-coated BioBullet capsule, which is released into theclogged pipe, contains salt-based toxins that are lethal to zebramussels. the mussels are then flushed out of the water pipe; anyBioBullets not taken up by mussels dissolve into harmlesscomponents. the technology provides a practical solution thatdoes not affect the treatment process or water quality.

the research has been of great interest to the UK waterindustry, with four companies funding the research to date.now, following approval by the Drinking Water inspectorate,trials have begun with Anglian Water Services Ltd to use thepellets in the UK for potable water systems. A newmanufacturing site is under way for BioBullets following anaward of £500k by the technology Strategy Board (tSB), which isbeing match-funded by Anglian, thames Water and tastetech.

Barrie holden, Water innovation manager at Anglian Water,said: ‘We are very encouraged that this technology will have asignificant impact on the ability of our water treatment works to

receive the required volume of raw water by limiting theinfestation. the technology potentially provides an economicand environmentally sound solution to a persistent problem.’ Dr Aldridge added: ‘Working closely with Anglian Water andother water industries is giving us new insight into how best toformulate and deliver the BioBullets solutions.’

For more information, please contact Dr David Aldridge([email protected]).

BioBullets mussel in on water mainsPipes blocked by an invasion of freshwater mussels pose a severe problem to the water industry.A tiny, fat-coated capsule could provide the answer.

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Dr David Aldridge and zebra mussels

PneumaCare is solving the problem of how to monitor lungfunction in babies, children and chronically sick patients using a non-invasive medical device. the idea for the device,which combines innovative image processing with technologies from the gaming and movie industry, has been developed by a consortium of experts that includes Dr Joan Lasenby at the Department of engineering, Dr Richardiles at Cambridge University hospitals nhS foundation trust and Dr Colin Smithers of Plextek Ltd.

the company represents a new and interesting departurefrom the usual spin-out model, as Dr gareth Roberts,PneumaCare Chief executive, explained: ‘Recognising an unmet medical need, the company consulted and utilisedUniversity expertise to create an innovative product. We havedeveloped a close working relationship with the academicsinvolved and, to cement this relationship, the academic partners have become equity holders. the success of this model ensures that the University shares in the company’ssuccess.’

PneumaCare will present data from its first product,PneumaScan™, over the next few months. ‘We believe that the

PneumaScan will make monitoring feasible, effective andsimpler, leading to better patient recovery,’ said Dr Roberts. ‘Wehave generated considerable interest in the investmentcommunity and are poised to go into full clinical developmentand medical trials.’

Part of this investment has come from the newly createdUniversity of Cambridge Discovery fund, which is managed byCambridge enterprise Ltd. the fund was created to smooth thepath of transferring University-related technologies for the benefitof society by providing proof of concept, pre-licence, pre-seedand seed investments, and is capitalised from donations throughthe University of Cambridge 800th Anniversary campaign.

For more information about PneumaCare, please visit www.pneumacare.com/For more information about the University of CambridgeDiscovery Fund, please contact Cambridge Enterprise Ltd(Tel: +44 (0)1223 760339; email:[email protected]) or visitwww.enterprise.cam.ac.uk/

A new model for industrial–academic partnershipPneumaCare, the first company to receive funding from the University of Cambridge DiscoveryFund, is a new model for utilising academic expertise.


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An innovative tool to image artwork hasresulted from a partnership between artconservators at the hamilton Kerrinstitute (hKi), a research department ofthe fitzwilliam museum, and SmartDriveLtd, a Cambridge-based company thatspecialises in precise motor controlsystems.

SmartDrive usually work withelectromechanical companies needingprecise motion control for roboticassembly lines and scientific

instrumentation. But for this venture, theyturned to the hKi, a centre of excellencefor conservation services and worldrenowned for its research on oil andtempera easel paintings.

the aim of the joint venture was touse tools that SmartDrive had developedfor science and technology applicationsto create a scanning system to guide artconservation. the result, SatScan, iscapable of revealing hidden layers ofpaint, as Chris titmus, imaging consultant

at the hKi, explained: ‘the information thatSatScan provides guides the restorationprocess and enriches the history of thework. it can also help with authenticationby revealing details that may showconsistency with a certain artist.’

Detailed topographical surface datafrom the artwork are captured using amoving camera that, under computercontrol, ‘flies’ in front of the painting.high-resolution digital images in visiblelight, infrared and ultraviolet parts of thespectrum are used to visualise under-drawings or to examine previous re-touching. the system speeds up apreviously manual, cumbersome processand extends the size and range of workthat can now be scanned.

Dennis murphy, managing Director ofSmartDrive, said: ‘Without hKi’s expertknowledge of the area, and capacity toput SatScan through its paces in aworking environment, we could neverhave developed a tool that we feel is asignificant breakthrough for artrestoration.’

For more information, please contactChris Titmus ([email protected]) or visitwww-hki.fitzmuseum.cam.ac.uk/ orwww.smartdrive.co.uk/

the Prisons Research Centre inCambridge’s institute of Criminology hasbeen working in and with prisons for thepast decade, carrying out a programmeof empirical research that is helping toinform policy and operational decisionmaking in prisons.

‘All prisons have strengths andweaknesses,’ explained Centre DirectorProfessor Alison Liebling, ‘but how prisonauthorities go about objectivelyevaluating the quality of prisons hassuffered from a lack of systematicresearch on what matters most, and hasfailed to link differences in prisonorganisation and culture to outcomessuch as suicide and reconviction.’

Aiming to fill this gap, ProfessorLiebling and colleague Dr Ben Crewehave spent almost three yearsinterviewing senior managers, staff and

prisoners at public and private prisonsacross the UK. the study, funded by theeconomic and Social Research Council(eSRC), draws on the trust and credibilitythey have developed over many yearsthrough engagement with practitionersand prisoners.

in piecing together the complexinterplay of values, practices andoutcomes that define the relative successand failure of prisons, the net result of thisstudy, building on several others, hasbeen the development of a survey-basedmanagement tool with which prisons cannow measure their own performance.‘Using the tool, we’ve found some reallyclear patterns that show what makes anestablishment work well and where thereis cause for concern,’ explained ProfessorLiebling. ‘the prison managers we’veworked with have been extremely

receptive and are using the data as abasis for strategic planning.’

Phil Wheatley, Director general of thenational offender management Service,which is responsible for delivering prisonand probation services on behalf of theministry of Justice, added: ‘this researchhas enabled the Prison Service to betterunderstand how prison management canbe more effective and to betterunderstand the complexity of the prisonofficer role. Specific deliverables include anew anti-suicide policy, which hassubstantially reduced suicide, and asurvey for measuring prisonerperceptions, which has been used tojudge the success of our prisons.’

For more information, please contactProfessor Alison Liebling([email protected]).

A measure of prison performance Pioneering research by Cambridge criminologists is helping prison managers to understandwhat makes a good prison.

Innovative tool reveals the paintings hidden withinThe development of optics that ‘fly’ over paintings could revolutionise art conservation.

SatScan in operation

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for centuries, books have played a centralrole in education, the spread ofknowledge and the cultivation of literaryand scholarly debate. With its originsdating back to the 15th century, thepublishing of books is the oldest of themedia industries and one which hascontinued to flourish despite theprofusion of other media forms. however,over the last 30–40 years, the industry hasgone through a process of turbulentchange stemming from forces that arepartly commercial, partly technological.thanks to these developments, it bearslittle resemblance today to the industrythat existed in the 1960s and before.

Despite these changes and despitethe continuing importance of books incontemporary culture, there has beenvery little systematic research on themodern book publishing industry.historians have studied the book tradeand the impact of books in earliercenturies, but the modern publishingbusiness has been largely neglected byresearchers.

it was partly to fill this gap in ourknowledge that i began in 1999 to studythe changing structure of the industry inBritain and the United States. theresearch, spanning a decade, was fundedby two grants from the economic andSocial Research Council (eSRC). While thefirst phase of the research focused onacademic publishing, the second phase,begun in 2005, was concerned withmainstream trade publishing – the worldof general interest books, aimed at thewider public and sold through high-streetbookstores, supermarkets and theinternet. this is the sector of publishingthat produces bestsellers like Dan Brown’sThe Da Vinci Code – books that are widelyreviewed in the press, prominentlydisplayed in bookstores and, in somecases, turned into films.

What makes a bestseller? Why dosome books take off and becomerunaway successes while thousands ofothers vanish without a trace? What arethe changes that have swept through theindustry and how have they affected thenature of what gets published and whatsucceeds? What impact have thesechanges had on the character of ourliterary culture, and what impact are theylikely to have in the years to come?

Three key developmentsto address these and other questions i immersed myself in the world of tradepublishing in Britain and the USA. i interviewed senior managers, editorsand other staff at all of the large tradepublishing groups in London and new

york, as well as many staff working insmall and medium-sized publishinghouses; i also interviewed agents, authors,scouts and booksellers – altogether, i didmore than 250 interviews with keyplayers in the industry. this enabled meto build up a detailed picture of how theindustry works, how it has changed overthe past few decades and how it ischanging today.

i was able to show that three keydevelopments have shaped the evolutionof trade publishing in the english-speaking world since the 1960s. the firstwas the growth of the retail chains, likeWaterstones in the UK and Barnes &noble in the USA. these nationwidechains of book superstores transformedthe landscape of bookselling in the 1980sand 1990s; they made books much morewidely available, but at the same timethey drove many smaller independentbooksellers out of business.

the second development was the riseof the literary agent. Although not new –the first agents appeared in London atthe end of the 19th century – literaryagents have, since the 1970s, becomemuch more powerful brokers in the fieldof trade publishing. they control accessto new content and, through auctions,are able to raise the stakes for books thatare perceived to have high sales potential.

the final development was theconsolidation of publishing houses underthe umbrella of large multimediacorporations. many of the great

The futureof books

Merchants of Culture: the Publishing Business in the21st Century by Professor John B. Thompson willbe published in 2010 by Polity

The book publishingindustry has gone throughmore change during thepast few decades than inany comparable period inits 500-year history.Professor John Thompsonexamines this change andasks what impact it willhave on the future ofbooks.


PRevieW

publishing houses whose names are wellknown to us all – Penguin, Jonathan Cape,macmillan, Knopf – are today owned bylarge corporations and survive as imprintsrather than as independent publishinghouses.

Making bestsellerstogether, these developments havecreated a field of cultural activity that has adistinctive structure and dynamic – a ‘logicof the field’. they have led, for instance, tothe polarisation of the industry, with four orfive large corporate groups dominating thefield and a plurality of small independentpublishers on the margins. very fewmedium-sized independent publishersremain active: in this new world of tradepublishing, it is very difficult to be medium-sized.

these developments have also led to apreoccupation with what in the industryare commonly known as ‘big books’. theseare not yet bestsellers but rather ‘hoped-forbestsellers’. given the unavoidable roleplayed by serendipity in trade publishing,it is simply unclear how well many newbooks will do in the marketplace – no-onereally knows.

So how do publishers decide howmuch they’re willing to pay for them?various factors come into play here, but acrucial role is played by ‘the web ofcollective belief’ which is built up throughthe numerous conversations that takeplace between agents, editors and otherplayers in the field. in the absence of

anything solid, the expressed enthusiasm(or lack of it) of trusted others is decisive.

the focus on big books is exacerbatedby the financial pressures on the publishinghouses owned by large corporations andby the practices of the retail chains, whichorder large quantities of some new books,charge publishers a premium for front-of-store displays and expect them to turn overquickly. many new books fail to take off andare sent back to publishers in largenumbers, resulting in historically high levelsof returns. But in those cases where theydo take off, publishers and booksellersmobilise quickly behind them, withadditional resources and promotion,pouring more fuel on the flames – this inpart is how bestsellers are made.

The end of the book?today trade publishers are faced withunprecedented challenges. the economicclimate is tough, overall sales (especially innorth America) are down and the arrival ofa new generation of ebook readers hasraised fresh questions about the future ofprinted books. Do these developmentsmean that the world of the book as we’veknown it is about to undergo a furthertransformation, even more radical than thatwhich has characterised the industry inrecent decades, perhaps even leading tothe eclipse of the printed book as such?

Despite widespread speculation aboutthe ‘end of the book’, we are still a long wayfrom a world in which trade books areroutinely read on screens rather than on

For more information, pleasecontact the author Professor JohnThompson ([email protected]) atthe Department of Sociology(www.sociology.cam.ac.uk/).

the printed page. Although ebooksales have increased significantly inrecent years, especially in the USA,they still account for only around 1%of the revenues of trade publishers – a tiny fraction. this is bound toincrease as reading devices becomemore widely available but no-oneknows exactly how significant it willeventually become.

Whatever happens, it seems likelythat books will continue to play animportant role in our cultural andpublic life for the foreseeable future.Books have been, and remain formany, a privileged form ofcommunication, one in which thegenius of the written word can beinscribed in an object that is at once amedium of expression, a means ofcommunication and a form of art. forthe telling of extended stories or thesustained interrogation of our ways ofthinking and acting, the book hasproven to be a most satisfying andresilient cultural form, and it is notlikely to disappear soon. But howbooks will be produced and delivered,and where they will fit in the newsymbolic and informationenvironments that are emergingtoday, are questions to which thereare, at present, no clear answers.

Professor John Thompson


feAtUReS

Deep below the Bay of Biscay, where theenglish Channel meets the Atlanticocean, layers of sediment hold preciousinformation about how Britain came to beseparated from mainland europe. Untilrecently, the clues had remained hidden,off limits owing to the impracticalities andcost of obtaining long-piston coresamples and high-resolution acoustic datain this area. however, thanks to an Anglo-french collaboration between ProfessorPhil gibbard, who leads the QuaternaryPalaeoenvironments group in theDepartment of geography, and PhDstudent Sam toucanne and his colleaguesfrom the University of Bordeaux, theseabed has now yielded its secrets. indoing so, it provides the final instalmentin a story that has been unfolding for twodecades, since Professor gibbard firstbegan his detailed palaeogeographic andpaleoenvironmental reconstructions ofthe southern north Sea.

When Britain actually was inEuropeBut the story really starts 500,000 yearsago, five ice ages before present times,when Britain was connected to europethrough a land mass that stretched fromthe netherlands to the Dover Strait.Between Britain and france was a wideshallow area into which southerly riverslike the Somme and the Seine drained,while the thames and the Rhine drainednorthwards into the north Sea.

indications as to what happened tothe landmass over the ensuing half amillion years have been found insedimentary investigations of thegeological history of the southern northSea region and neighbouring areas byProfessor gibbard. these provided a read-out of past environments, includingclimatic changes, and of how and wherethe rivers flowed during the past.together with bathymetric maps (sonar

readings of the floor of the englishChannel, showing the topography ofdeep valleys running the length of thewaterway), it has been possible to buildup a detailed picture of the conditions ofthe region: where rivers drained, glaciersformed and landmasses changed.

most recently, the scientists havebeen able to build up a continuousrecord of the earth’s climate variability forthe past 1,200,000 years, showing acorrespondence between temperaturechanges caused by the waxing andwaning of the glaciers and the peaks andlows in sedimentary deposits. the datashow that three of the five ice ages –450,000 years, 160,000 years and 30,000years ago – seem to have had the mostdramatic impacts on the sedimentarydeposits. Could one or more of these iceages have precipitated the events thatresulted in Britain becoming separatedfrom europe?

The latest instalment ofa 20-year study to

understand how Britainbecame an island

completes a tale ofmegafloods and

super-rivers.

Britain’s islandheritage:reconstructinghalf a millionyears ofhistory


Megafloods and super-riversthe first breakthrough came whenProfessor gibbard’s investigations of thesouthern north Sea region and review ofthe drainage systems led him to suggestthe existence some 450,000 years ago ofa massive lake. the meeting of a glacierflowing down across Britain from thenorth and a glacier advancing fromDenmark strongly modified the flowdirections of central european rivers,effectively blocking their flow into theAtlantic ocean. the result was the build-up of a large, freshwater, glacial lake,about the size of east Anglia, just north ofwhat is now the Dover Strait. the lake wasdammed by an ice sheet, landmass and,crucially, the upfolded spit of land thatlinked Britain and france at the DoverStrait.

the first morphological evidencecame to light in 2007 from bathymetricmaps of the english Channel. Dr Sanjeevgupta at imperial College Londonobserved that the existence of longgrooves of erosion and deep valleysrunning longitudinally along the bedrockfloor fitted with an extraordinaryconclusion. it seems that the freshwaterlake filled until, like an overflowing bath, itbreached the Dover Strait. A catastrophicdischarge of water surged at least onceand probably twice down the basinbetween Britain and france,overwhelming the rivers and streamsbelow it, and spreading out across thebasin as a megaflood. this massivesouthwards discharge of meltwatersmerged with the river-water from theSeine, Somme and others, to form the‘fleuve manche’ (Channel River)palaeoriver, one of the largest riversystems on the european continent.

further ice ages followed. each time,as the glaciers receded, sea levels roseand the Channel would continue to becarved out; as glaciers returned, sea levelsdropped and the landmass would oncemore connect Britain to the Continent. A second megaflood seems to havehappened 160,000 years ago, only thistime the gap at the Dover Strait wasenlarged enough that it would neverreform: Britain was now an island.

A full reconstructionthe recently published Anglo-frenchstudy has provided the final piece of thepuzzle by looking, for the first time, atwhat flowed out of the Channel into theBay of Biscay during these crucial periodsof Quaternary history. Corroborating thestory that had emerged from theupstream sedimentary analyses and thebathymetric data, this new research

demonstrates peaks and troughs in thecharacter and volume of the sedimentarymaterial relating to the interglacial andglacial periods. Significantly, at the timesidentified for the megaflood, thescientists found that the volume andcharacter of the sedimentary materialvastly increased, consistent with massivesurges in ice-rafted debris and sedimenthaving swept down the fleuve manchesuper-river and out into the Bay of Biscay.With this new research, there is now acomplete record that reconstructs thesedramatic and far-reaching events thatwere to give Britain its island status.

Like any other large-scalegeographical upheaval, the implicationsof the megaflood are profound. the largevolume of freshwater released into theAtlantic would have caused changes inocean circulation, with knock-on effectson the climate in an area stretching fromthe Bay of Biscay to north Africa. floraand fauna (including early humans)would also have been affected: duringinterglacial periods such as the one weare currently experiencing, the high sealevel would cut Britain off from mainlandeurope, forming a barrier to the migrationof humans, animals and plants alike. Butin glacial periods, the water level wouldfall and, although there would neveragain be a continuous landmass linkingBritain with europe, the Channel Riverwould provide a major migrationrouteway. in fact it was probably possible to wade across from france to Britain as few as 9,000 years ago, and this may yet be possible tens ofthousands of years from now, when we enter the next ice age.

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Professor Phil Gibbard

For more information, please contactProfessor Phil Gibbard([email protected]) at the QuaternaryPalaeoenvironments Group(www.qpg.geog.cam.ac.uk/) in theDepartment of Geography. Thisresearch was published in QuaternaryScience Reviews (2009) 28, 1238–1256and Nature (2007) 448, 259–260.

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The Dover Strait was formed in the last half amillion years when a massive lake, dammed tothe north by the European ice sheet, burstthrough into the English Channel

‘Scriptorium’ is the culmination of a three-year project in the faculty of english todigitise and preserve a type of manuscriptbook well known in 15th- to 18th-centuryeurope: the commonplace book ormanuscript miscellany. And at the heart ofthe project, which was funded by the Artsand humanities Research Council (AhRC),lies an innovative tool that will help you toread them.

A literary phenomenonCommonplace books were the personalorganisers of their day. Learned men (and,more rarely, women) would compile bookscontaining recipes, accounts, sonnets,quotes, prayers, songs, legal treatises andmedical instructions. Sometimes passedfrom one owner to another and continuedover decades, if not centuries,commonplace books would be filled withsnippets of contemporary information andculture. the keeping of such books wasregular practice in the period, enablingtheir owners to record and rememberwhat they had read, been told oroverheard. each is a unique collection ofknowledge: an intellectual scrapbook, thefilofax of its time.

A total of 20 commonplace books andmiscellanies forms the backbone of theScriptorium project. these books have

A scriptorium ofcommonplace books

A digital archive of 500-year-old ‘filofaxes’ offersextraordinary insight into early thought and

writing practices.

been sourced fromCambridge collegelibraries and theUniversity Library, aswell as from archivesin country houseslike holkham hall in norfolk. Somehave a knownprovenance, suchas a 17th-centurybook of estatemanagementwritten byWilliamheveningham,part of whichwas writtenduring his

18-year incarceration in WindsorCastle for his role in Charles i’s execution.the glastonbury miscellany (c. 1450), a114-page collection of literary texts inLatin and english, started life as aglastonbury monk’s accounts book and,after successive interventions by five morescribes, was still being added to a centurylater.

Daleks aid digitisationover the course of three years, the projectteam, led by Drs Richard Beadle, RaphaelLyne, Andrew zurcher and Colin Burrow,adapted and developed painstakingtechniques to minimise the risk of damageto texts during photography. ‘Daleks’,made from an aluminium bolt and twosewing needles, provided one means ofsafely applying adjustable levels ofpressure on manuscript leaves, to lay themflat for photography. Project researchers,including Drs Christopher Burlinson,Angus vine and Sebastiaan verweij, alsopioneered new descriptive methods andrepresentational strategies for publishingrare manuscript materials online, includingfull and searchable analyses of eachmanuscript, and transcriptions of keyselections.

Working in collaboration with theCentre for Applied Research in educationaltechnologies (CARet), and it developermariko Brittain, the team also developedan expansible, automated manuscriptimage database that will continue to

function and grow beyond the life of thefunded project. And with conservation inmind, high-resolution manuscript imageshave been securely dark-archived inDSpace@Cambridge, CambridgeUniversity Library’s digital repository.

Help with handwritingthe art of deciphering old handwriting,known as palaeography, is a difficultdecoding process that can becomplicated by factors such as the scribe’sstyle, evolving letter-forms and unusualpunctuation. help in cracking this code isnow available from the Scriptoriumproject’s fully interactive online englishhandwriting course. the course makes fulluse of the wide range of hands, styles andidiosyncratic habits represented by theScriptorium project manuscripts, whichwere chosen with an eye to theirpalaeographical range and complexity.

this and other resources within theScriptorium project are dovetailing withteaching and research in the faculty ofenglish, opening up the literature, history,theology and philosophy of earlier periodsto a new generation of students andscholars in Cambridge and across theworld.

Dr Raphael Lyne, Dr Richard Beadle and Dr Andrew Zurcher

(left to right)

For more information, please contact Dr Richard Beadle([email protected]), Dr Raphael Lyne([email protected]) and Dr AndrewZurcher ([email protected]) at the Faculty of English or visitScriptorium (http://scriptorium.english.cam.ac.uk/).

A miscellany ofhousehold information compiled in

the 15th century; MS Ll.1.18.9v

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in these globalised times, wheninternational communication has takensome endangered languages to the pointof extinction, it is fascinating to considerhow one nation has resisted theencroachment of other languages in theinterests of keeping its language pure.

the french have long been keenadvocates of linguistic correctness or‘good usage’. indeed, it is often said thatfrance provides the most extremeexample of a prescriptive, interventionistand purist attitude to use of language.even today, ministerial commissionsrecommend acceptable terminology forfields as diverse as it and nuclear energy,and the Académie française (the frenchlanguage academy), advises on properusage of french vocabulary and spelling,as it has done since the 17th century.

in a major research project funded bythe Arts and humanities Research Council(AhRC), Professor Wendy Ayres-Bennett is directing a collaborative projectresearching the origins of this concern forlinguistic correctness and the broadersymbolic values associated with it.

Remarks and observationsthe french preoccupation with languagepurity is reflected in the founding of theAcadémie française in 1635 and, perhapsabove all, in the publication of aparticular type of metalinguistic work. in1647, Academy member Claude favre devaugelas published his Remarques sur lalangue française, a collection of short,randomly ordered remarks andobservations intended to resolve pointsof doubtful usage and provide clearguidance on the good use of french.

vaugelas’s book quickly became abestseller and was highly influential. Weknow, for instance, that in 1660 the greatplaywright Pierre Corneille reworked thelanguage of his plays to take account ofvaugelas’s judgements and that JeanRacine, author of some of france’s finesttragedies, is said to have taken a copy ofthe work with him to the south of franceso as not to become ‘contaminated’ byregional speech.

to understand theappeal and influenceof such works in theirday and beyond is toexamine the socialand cultural history of france. in a period of great socialmobility, whennobility could bepurchased by thenewly rich, thevolumes acted as a kind oflinguisticcourtesy book.Someonearriving new to theKing’s court would need to know notonly how to dress and eat properly, butperhaps above all how to speak correctly,so as not to offend polite society.

A rich resource many volumes of remarks andobservations have been published byvarious authors down the centuries. Allare typically intended not for foreignersbut for competent native speakers whowish to perfect their usage of french.

these volumes provide the focus ofthe research project, which bringstogether scholars from north America,france and other parts of europe toaddress key questions about the genreand to create a corpus of the principaltexts, to be published online and ascritical editions. this valuable researchtool will provide those working oncontemporary french with a historicalperspective to their research: many of themost troublesome rules of frenchgrammar used today, including pastparticiple agreement, date from theseearly remarks on the french language.moreover, one of the most fascinatingaspects of the research is that thevolumes of remarks provide unique dataon how people actually wrote and spokein the period.

the writers of remarks continually strivedto define what is french and to excludethe unwanted ‘other’, whether this isregional, low-register or foreign usage.notions of language, nation and identityare thus closely intertwined. in short, to research the history ofstandardisation and linguistic correctnessin france involves consideration of whatit is to be french.

Le bon usage: usingFrench correctlyThe purity and linguistic correctness of theFrench language has been closely guardedby the French for centuries. Professor WendyAyres-Bennett is exploring the reasonsbehind this national preoccupation.

For more information, please contactthe author Professor Wendy Ayres-Bennett ([email protected]) at the Department of Linguistics(www.mml.cam.ac.uk/ling/).

Professor Wendy Ayres-Bennett

Frontispiece ofVaugelas’s Remarques sur la languefrançaise (1647)

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Pandemic h1n1 virus infection – or‘swine flu’ – has spread globallyfollowing its emergence in mexico inmarch 2009. millions of people havebeen infected and, as of December2009, over 9,500 deaths have beenreported to the World healthorganization (Who).

governments and individuals areunderstandably concerned: this is thefirst human influenza pandemic in morethan 40 years. Although a ‘bird flu’pandemic has been feared since 1997,no more than a few hundred peopledied of avian h5n1 influenza, despitebeing spread by migratory birds andthe international poultry trade. Puttingthis in context, hundreds of thousandsof people globally continue to die fromseasonal influenza each year.

not only do severe pandemics havefar-reaching repercussions for humanhealth, the health sector and theeconomy, but influenza outbreaks infarmed animals also have a profoundimpact on the consumer market andloss of business. new research on theorigins, spread and prevention of swineflu is urgently needed to informgovernment policy on how futurepandemics like the one we are currentlyexperiencing can be detected,controlled and ultimately prevented.

A coordinated researchresponsein what has been described as amongthe fastest reactions of the UK scienceand funding community to an emergingdisease threat, leading UK researchfunders announced in november 2009funding of £7.5 million aimed atunderstanding the development andspread of pandemic influenza. thiscoordinated response from the researchcommunity was catalysed by the medicalResearch Council (mRC), Wellcome trust,Biotechnology and Biological SciencesResearch Council (BBSRC), Department ofhealth and Department for environment,food and Rural Affairs (Defra). the resulthas been the funding of four majorcollaborative projects (see panel).

in Cambridge, Professor James Woodat the Department of veterinary medicineleads a study to monitor the spread andevolution of influenza in infected UK pigherds and farm workers, bringingtogether a multidisciplinary team of 18 researchers from Cambridge, oxford,edinburgh and London. A sister projectled by Professor ian Brown at theveterinary Laboratories Agency (vLA),Weybridge, focuses on the transmission,infection dynamics and immunopathologyof h1n1 in pigs compared with humaninfection. together, the two projects form the Combating Swine influenza(CoSi) initiative.

Viral ‘mixing vessels’ the new research builds on a programmeof study carried out by the Cambridgeinfectious Diseases Consortium (CiDC),which has been investigating infectiousanimal viruses that pose a major diseasethreat to both animal and humanpopulations. the CiDC is led by ProfessorWood in the Department of veterinarymedicine and operates in closecollaboration with the Animal healthtrust (Aht) in newmarket.

A large part of research within theCiDC focuses on swine h1n1 and equine h3n8 viruses. Swine flu iscommon in pigs in europe and circulates through farms on at least anannual basis. equine influenza virus also circulates endemically in the UK,predominantly affecting younger horses. Working closely with theinternational and national referencelaboratories for swine and equineinfluenza – the vLA and the Aht,respectively – and collaborating with the Wellcome trust Sanger institute,researchers at the CiDC are aiming toexamine genetic variation withinendemic viruses.

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‘This is amongst thefastest I have ever seenthe UK sciencecommunity react to anemerging disease threat.Turning around afunding initiative in amatter of months whileensuring we aresupporting the bestscience has been a hugeachievement by thescientific communityand the funders.’Professor Douglas Kell, BBSRCChief Executive, commentingon four new collaborativeprojects being funded acrossthe UK, one of which is beingled by Cambridge.

Influenza virus


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this latest strain of swine flu, forinstance, is known to have arisen from thecombination of two swine influenzaviruses, one originating in the USA andthe other in europe. it seems thatprogenitor viruses were circulatingundetected, probably in pigs, for aroundnine years before the jump to humanstook place. Pigs are especially likely to bea ‘mixing vessel’ for viruses because theyare more susceptible to a range ofinfluenza viruses than most other animals.

By examining genetic variation withinendemic swine and equine viruses, thescientists hope to understand how virusvariants, which usually arise at a lowfrequency, end up being spread betweenanimals and populations. Usingepidemiological and experimental data,they are constructing mathematicalmodels of virus infections, examiningquestions relating to the control ofinfection within the host animal, thespread and control of viruses throughpopulations and how the gradualevolution of the influenza virus reaches athreshold before large-scale outbreaks orepidemics are likely to be observed.

The COSI Initiativethe newly funded research initiative isintended to develop a vital newunderstanding of how the pandemich1n1 virus behaves in pig populationsand how interaction with farm workersmay help it to evolve and spread. Withthis information, it should be possible tomove a step closer to developingstrategies to slow or prevent the spreadof the virus in both pig herds and thehuman population.

the collaboration led by ProfessorWood aims to define the consequencesof what would happen if the pandemich1n1 virus spreads from humans to pigs,as has happened in countries as diverseas Argentina, USA, Canada, northernireland and Australia, probably following

Combating Swine Influenza (COSI) Initiative: the role of pig–pig andpig–human interactions in the development and spread of pandemic h1n1:• epidemiological and evolutionary investigations in pigs and farm workers

(University of Cambridge)• immunological and dynamic modelling of infection in pigs compared with

humans (Veterinary Laboratories Agency, Weybridge)

FluWatch: study of the transmission of pandemic h1n1 within households inengland (University College London)

MOSAIC: study of hospitalised cases of severe infection (Imperial CollegeLondon)

the infection of pig farmers who havethen transmitted the virus to pigs. inBritain, many pigs are farmed in largepopulations and, if these farms were tobecome infected with the pandemic fluvirus, then large amounts of virus wouldbe produced with unpredictableconsequences.

Detailed genetic studies of archivedsamples from previous swine influenzaoutbreaks will be carried out, as well asan investigation of the health of pigfarmers and vets who are exposedthrough their occupation to theseoutbreaks. this will provide a betterexplanation of how the pandemic virusarose and spread, including where theinitial virus combination took place. Withthis information, the likelihood of similarevents reoccurring can be predicted andrecommendations for minimising theongoing risk can be made.

Another important area will be topredict the immediate threat if thepandemic virus mutates to become amore virulent form, particularly ifpandemic h1n1 becomes endemic in thepig population. the rates of viralmutation will be studied and any specificvirus mutations associated with thespread between pigs and people working

with pigs will be identified. Data fromaffected farms will be used to makeaccurate models of transmission anddynamics to help inform interventionstrategies.

Informing policytogether, the four newly fundedcollaborative projects aim to understandhow the virus mutates and jumps thespecies barrier and how it spreadsthrough communities; how the viruscauses disease in both pigs and humansand why it affects some individuals morethan others; and which interventions aremost effective at preventing infection ortreating the disease. the intention is forthe results to feed directly into widerpolicy analysis on dealing withpandemics, for the long-term benefit ofhuman and animal health.

Scientists from the Department of Veterinary Medicine and the Wellcome Trust Sanger Institute will beworking together to understand swine flu; left to right: Professor James Wood, Dr Greg Baillie (Sanger), Dr Pablo Murcia, Dr Paul Kellam (Sanger)

For more information, pleasecontact Professor James Wood([email protected]), the AlboradaProfessor of Equine and FarmAnimal Science, at the Departmentof Veterinary Medicine, or visit the CIDC website(www.vet.cam.ac.uk/cidc/). The COSI Initiative is funded by the BBSRC, Defra, MRC andWellcome Trust.

Professor James Wood

Newly funded collaborative projects on H1N1

Developmental dyslexia, which manifestsas a difficulty in reading and spelling,affects about 7% of schoolchildren, mostlyboys, and presents a major obstacle toeducational success, future mental healthand lifetime earning. its mathematicalcounterpart, developmental dyscalculia,affects about 6% of schoolchildren and isfound equally in boys and girls. Accordingto figures released from the UKgovernment office for Science, dyscalculiahas an even higher impact on educationalsuccess than dyslexia.

early diagnosis and appropriateeducational support are known to havelasting benefits for children and adultsaffected by these disorders. to get thisright, a better understanding is needed of how the brain acquires reading andmaths skills, and the new field ofeducational neuroscience is helping tofind the answers. in the forefront of these studies is Cambridge’s Centre forneuroscience in education. With £2 million recent funding from themedical Research Council (mRC), theresearchers at the Centre aim to discover neural markers for dyslexia and dyscalculia through brain imagingtechniques. this will enable affectedchildren to be identified as early aspossible and for targeted remediation to be delivered.

A world firstthe Centre for neuroscience in educationwas the first neuroscience laboratory inthe world to be established within afaculty of education. Launched formally in2005, with an inaugural conference thatattracted 220 teachers and educators fromover 15 countries, the Centre now has ateam of 24 students and researchers. Staffare trained in a variety of disciplines,spanning psychology, education,medicine, linguistics and physics. theCentre is directed by Professor Ushagoswami, with Dr Dénes Szűcs asUniversity Lecturer in neuroscience andeducation.

From electrochemical signalsto educationthe main brain imaging technology used in the Centre is theelectroencephalogram (eeg), a techniquethat can measure the voltage changesthat are caused by the electrochemicalactivity of brain cells. Whenever a child (or adult) is thinking or feeling, tinyelectrical changes occur in the brain. thesechanges can be measured by sensitiveelectrodes that are placed on the skin ofthe scalp, mounted in a special hairnetthat enables direct recordings of brainactivity to be taken. the technique is


For some children,acquiring the importantskills of learning to read ordo arithmetic is fraughtwith difficulty. Educationalneuroscience is helping tounderstand why.

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A special hairnet collects data from a young participant in the developmental dyslexia project


painless, the electrodes are easy to put onand the children enjoy the measurementsessions.

But how can these electricalmeasurements tell us anything about theprocess of learning? A developmentaldyslexia project is making this link byfollowing over 100 children on a yearlybasis for five years, making brainmeasurements at the same time asanalysing speech processing, auditoryprocessing, reading and spelling. one area of particular focus is a specific difficultyin processing the sound patterns of words,a skill called phonological awareness,which has been known for over 20 years tobe the hallmark of developmental dyslexia.

The sound of syllablesChildren with dyslexia find it difficult todecide whether words rhyme and to count the number of syllables in a wordlike oasis. one reason is that aspects of the auditory signal in speech are processed less efficiently by the dyslexicbrain.

in a simple auditory tone task that hasnow been used with dyslexic childrenlearning languages as diverse as english,Spanish, Chinese and finnish, scientists atthe Centre have shown that one particularsound parameter is more difficult todiscriminate. A bit like the difference in theonset of loudness between a trumpet noteand a violin note, there is a difference inthe rate of onset of loudness that occurs aswe produce syllables; the Cambridgeresearchers have found that this is impairedin developmental dyslexia. in fact, thisprocessing difficulty means that childrenwith dyslexia are impaired in any auditoryrhythmic task – including perceivingmetrical structure in music and tappingalong to a beat.

Reading in rhythmto further complicate matters, the way inwhich the pre-literate brain representslanguage is fundamentally different to the

way in which the literate brain representslanguage. Learning to read changes thebrain because learning an alphabet makesus conceptualise spoken words in terms oftheir spelling patterns. We automaticallyhear spoken language as a series of thekinds of sounds represented by letters (e.g.we hear cat as c + a + t); this connectionbetween sounds and letters is calledphonics. the dyslexic brain does not havethe auditory distinctions efficiently in placeto which phonics instruction can be easilylinked.

Currently, the main remediation offeredto children with developmental dyslexia isyet more intensive instruction in phonics.instead, the research in Cambridgesuggests that interventions based onrhythm and even music may be beneficial,at much earlier ages. Rhythm is more overtin music than in language, and otherprojects at the Centre have shown thatbeing able to sing in time with music ispredictive of syllable and rhyming skills,and that training in rhythm improvesphonological awareness. Severaleducational interventions based onmusical and speech rhythms are currently being developed at the Centre.

Magnitude of the problemthe mRC project on dyscalculia is justbeginning but, here too, the neurologicalbasis of the disorder is under scrutinybecause a distinct area in the brain’sparietal cortex seems to be specialised forunderstanding magnitude. Children withdyscalculia have enormous difficulties inmaking decisions about quantities, suchas ‘how much is four?’ intriguingly,however, scientists at the Centre haveshown that the main sensory marker ofmagnitude difficulties – being slower tomake judgements about numbers that arecloser together than further apart – is not deficient in children with dyscalculia.But these children do have very poorworking memories, finding it both difficult

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Professor Usha Goswami

For more information, please contactthe author, Professor Usha Goswami([email protected]), at the Centre forNeuroscience in Education(www.educ.cam.ac.uk/centres/neuroscience/) in the Faculty ofEducation. Research at the Centre isfunded by grants from the MRC,Economic and Social ResearchCouncil (ESRC), European Union,Leverhulme Trust and NuffieldFoundation.

to keep relevant information in mindand to recognise mistakes.

When children start learning mathsat school, changes largely occur in thelanguage areas of the brain. theensuing neural connections that formbetween memory, magnitude anddecision-making processes mayunderlie what goes wrong indyscalculia. this hypothesis will beexplored using a variety of non-invasiveimaging techniques at the Centre andin collaboration with the mRCCognition and Brain Sciences Unit inCambridge, in an effort to use spatialimaging technologies to deliver exactinformation about where the affectednetworks are in the brain.

With foresightthe Centre is also beginning to havean input into government policy.Professor goswami was the scientificco-ordinator for Learning Difficultieswithin the government office ofScience ‘foresight’ project on mentalCapital and Wellbeing in 2008, one ofthree Cambridge scientists in the leadteam (along with Professors BarbaraSahakian and felicia huppert). if therecommendations of the foresightproject are implemented nationally,then the insights from brain science foreducation will eventually be reflectedin the basic training of all the teachersin the country. When that happens, allUniversity Departments of educationwill need some expertise in brainscience – and Cambridge will be in thevanguard once again.

The Centre for Neuroscience in Education team

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the British Academy receives £22 millionin government grant to support UK-based research and internationalcollaboration in the humanities andsocial sciences. from this, over 1,000awards are made each year, benefitingindividuals based in more than 120universities and research institutionsacross the UK.

Supporting researchone of the most popular British Academyfunding programmes is the Postdoctoralfellowship. these provide three-yearcareer development opportunities toscholars such as Dr Matilda Mroz andDr Zoltán Tiba (see panels) to developresearch, teaching and publications at an early career stage. Around 45 newawards are made annually under thisexceptionally competitive flagshipscheme, including seven to Cambridgethis year.

British Academy ResearchDevelopment Awards (BARDAs) supportestablished scholars wishing to develop asignificant collaborative or individualresearch project. About 35 awards aremade each year under this comparativelynew scheme, which replaces largeresearch fellowships and research leave.in Cambridge, BARDA-funded scholarsinclude Dr mandeep Dhami, who isevaluating apology in the context ofrestorative justice, Dr Claire Preston, whois studying 17th-century english literatureand scientific investigation, and Dr AnnaWilliams, who is researching thearchitecture of theology.

the Academy also offers SmallResearch grants (up to £7,500) tostimulate interdisciplinary work,collaborations or pilot studies, and severalschemes focus on encouraginginternational collaboration, promotingcapacity development and engagement.for instance, the three-year UK-AfricaAcademic Partnership award encourages

institutional links and promotes newunderstandings and interchangebetween participating countries. inCambridge, Dr Devon Curtis is using thisaward to collaborate with scholars inUganda and Botswana on a study ofrebel movements and post-conflictpeace building in Africa.

the British Academy is thecounterpart to the Royal Society, whichsupports the natural sciences. theAcademy partners with the Royal Societyand the Royal Academy of engineeringfor the esteemed newton internationalfellowships scheme, which aims to builda global pool of research leaders andencourage long-term internationalcollaboration.

Championing humanities andsocial scienceseach year, the Academy elects 38outstanding UK-based scholars to befellows of the British Academy inrecognition of their researchachievements. today, there are over 900fellows who take a lead in representingthe humanities and social sciences, andwho contribute to public policy anddebate. Seven Cambridge academicswere among the recently elected fellows:Professor Simon Baron-Cohen, ProfessorPhilip ford, Professor Jonathan haslam,Professor mary Jacobus, Dr Johnmarenbon, Professor Susan Rankin andProfessor John Duncan.

through investing in ideas, individualsand intellectual resources, the Academyaims to enhance the scholarly andcultural resources of the UK, contributingto quality of life, economic prosperity,public policy, understanding of othersocieties and cultural enrichment.

For more information about the British Academy, please visitwww.britac.ac.uk/

Polish cinema inthe frame

The UK’s national academy for the humanities and socialsciences seeks to recognise and support leading-edgeresearch within these fields, championing their importanceand the vital role they play in raising and answeringfundamental questions facing society today.

Cinema was a central means ofcultural expression in post-warPoland. Dr Matilda Mroz isasking how and why.

‘Watch them closely, for these are the lasthours of their lives…,’ commands thenarrator at the beginning of the Polishfilm Kanal (1956), directed by AndrzejWajda. And watching closely, frame byframe, is precisely what Dr matilda mroz is doing, as she examines post-war Polishfilms for the nuances that escapedSocialist censorship and gave cinema ofthe time a unique political resonance.

‘Cinema is the most important artform to emerge in the 20th century,’explains Dr mroz, from the Department of Slavonic Studies. ‘in Poland, unable tocommunicate resistance to the Socialistregime through open political channels,oppositionists often chose to expressthemselves through culturally symbolicactions. Cinema became their mostpowerful tool, slipping subversive notionspast the censors through subtle cinematicdirection.’

Warsaw Uprising Memorial,Poland, on the 60th anniversaryof the Uprising


Dr Matilda Mroz

For more information, please contact Dr Matilda Mroz ([email protected])at the Department of Slavonic Studies(www.mml.cam.ac.uk/slavonic/).

For more information, please contactDr Zoltán Tiba ([email protected]) atthe Centre of African Studies(www.african.cam.ac.uk/).

Dr Zoltán Tiba

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funded through a British AcademyPostdoctoral fellowship, Dr mroz hasbeen tracing this trend in Polish film-making, a trend that is beautifullyexemplified by Kanal. Set among theruins of wartime Warsaw, Kanal depictsthe last days of the 1944 Warsaw Uprisingand the attempt of the insurgents toreach another part of the city throughthe sewers, in which they get lost andperish.

‘it was the first film that addressedthe previously taboo subject of the non-Communist resistance movement, and ittraumatised many viewers because itshowed the soldiers escaping and thendying in the filth of the sewers ratherthan fighting heroically,’ explains Dr mroz.‘even the cinematography was such thatviewers often spoke of feeling as lost andclaustrophobic as the characters – amarked departure from the rigorouslyframed films beloved of the Socialistmovement.’

Understanding how cinema-goersreacted to the films is an importantaspect of the research, since it affords aunique opportunity to examine theintersection between cinematicexperience, historical climate and Polishculture. Dr mroz’s funding enabled her totravel to Warsaw to the national filmArchives last year, where she made alucky discovery: ‘Sixty years ago,someone had diligently cut out everyarticle and mention of the very films thati was interested in and pasted them intoscrapbooks. there’s something veryexciting about opening these yellowing,crinkled books and thinking about thearchivists determined to preserve forposterity both the ‘official’ and thecontroversial responses to importantfilms.’ now, decades later, Dr mroz isrediscovering these invaluable recordsand their testimony to the enduringpower of cinema for the Polish people.

‘the nature of famine has changed,’ said Dr zoltán tiba, a British-Academy-fundedPostdoctoral fellow in the Centre of AfricanStudies. ‘today, famines happen not justbecause there is a decline in the availabilityor in the access to food, but because offactors such as the political economy andthe toll of hiv-AiDS on the workingpopulation.’

Dr tiba’s research has set out todevelop fresh analytical tools tounderstand famines. he takes malawi insub-Saharan Africa as his primary focus.‘malawi is an interesting case since in manyways it challenges commonly acceptedviews about the causes of famine. thefamine in 2002 demonstrated thatdemocracy does not always ‘end famine’.Contemporary famines have multiple andcomplex causes, and traditionalinterventions such as food aid distributionsare not necessarily the best solution to‘new’ famines.’

for the past seven years, Dr tiba hasbeen conducting research in a malawianvillage, where he has been interviewingvillagers and carrying out householdsurveys, as well as speaking to governmentofficials and aid agencies. his findings arebuilding a unique picture of village life andthe malawians’ experiences of foodinsecurity. ‘the area is a garden of eden,with lush vegetation and plenty of water

and, yet, chronic food insecurity is a seriousproblem and the threat of famines is stillevident.’

‘increasingly my research isemphasising the role of local attitudes todiversification of diet and production,’explained Dr tiba. ‘one possibility for long-term change at the macro level is to focuson the micro level – something as simpleas individuals growing fruits and raisingsmall livestock in addition to growingcereals would add to the safety net tosubvert chronic food insecurity andfamines in a country like malawi.’

Famine’s changing faceDr Zoltán Tiba’s research on why famines happen is posingquestions about the root causes and possible long-terminterventions.

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‘in two decades’ time, the expectation isthat india will have one of the world’slargest economies – a result of itsescalating engagement with innovation,its service economy and its young anddynamic population,’ explained ProfessorPrabhu. ‘it’s an incredibly exciting time tobe looking at the nation’s role in theglobal economy, both through the lens of innovation and from a systematicbusiness perspective.’

the Centre for india & globalBusiness, launched in march 2009 withstart-up funds donated by the BP group,has an overarching research theme ofinnovation and the role that it can play inindia. this stretches from how and whythe world’s largest multinationals areincreasingly locating their global R&D and innovation activities in india, how indian firms themselves areinternationalising and increasing theirglobal competitiveness, to howorganisations are actively innovating with those in india who live below thepoverty line to make their lives better.

Professor Prabhu brings to the Centrehis extensive research experience gainedin the USA, europe and the UK. AsDirector, his goal is to create acollaborative platform that draws inmultiple stakeholders from india, the UKand other countries. ‘it’s not just theresearch that counts, it’s also how wepromote and guide engagement withinnovation in india and, for this, the roleof other stakeholders will be crucial,’ heexplained. ‘By understanding some of thechallenges that lie ahead, we can help to derive solutions that will be ofwidespread benefit to the globaleconomy.’

What would others be surprised tolearn about you?When I was younger, I was obsessed withfiction and poetry. I was particularly fond ofthe poetry of Auden, Brodsky and Walcott,and the novels of Saul Bellow. I read widelyand went around with all these literarythoughts in my head, imagining that oneday I might be a poet. Although I took a

more conventional route and ended upstudying engineering and business, I’m stillfascinated by the written word.

Have you ever had a Eureka moment?I’ve had moments of dawning realisationthat have had a profound influence on me.Probably the most significant of these wasafter moving from India to the US to studyat the University of Southern California inthe early 1990s. I was swept away by theintellectual openness and I consideredswitching from engineering to philosophy. I also saw at first hand how differently toIndia the US operated in terms of the role ofthe state versus free enterprise. It was myfirst introduction to the complexitiesunderlying political economies worldwide.

What’s the best piece of advice you’veever been given?When I was wrestling with whether toembark on a philosophy doctorate, myuncle (himself a philosopher) suggested thatI choose business instead. Deciding againstphilosophy was very hard to accept then,but, as it turns out, he was absolutely right. I had grown up questioning why there isinequality in society, in particular why somepeople and countries are wealthy andothers are not. Studying business has givenme the tools to think about these questionssystematically. I like the fact that businessengages with the world and its social andeconomic prospects, and the fact that thereare constantly new questions to ask anddiverse theories and methods to use to findanswers to them.

What motivates you to go to workeach day?The idea that something I do might in some small way make a difference topeople’s lives. One aspect of the Centre’sresearch is looking at how business canhelp improve the lives of people who live onunder $2 a day – about 2.5 billion peoplearound the world, many of whom are inIndia. If you think about innovation as theshaping of technology to deliver newbenefits for people, then even the most basic innovations will improve lives,

provided a business solution can be foundto make them viable. Even something asbasic as using a mobile phone as a micro-payment system can open up enormousopportunities in a country like India, where60% of the population has no bank accountand, as such, remains outside the formaleconomy.

What’s your favourite research tool?It has to be statistics, both conceptually andas a practical, computer-based tool.Without statistics it is very hard to do anykind of systematic social science.

What will the future look like in 2050?The emerging markets will have emerged.Nations like India and China, as well asRussia, Brazil and countries in Latin Americaand Africa, will all have a bigger role to playon the global stage. There will be greatermovement of people, more diversity at work,increased democracy, and essentially amore connected world. With climatechange and population growth, we’ll facesignificant challenges, especially scarcity inenergy, food and water. But necessity is themother of invention and it is my belief thatwe will see some significant entrepreneurialand business solutions to the challengesahead.

Professor Jaideep PrabhuJaideep Prabhu is the first Jawaharlal Nehru Professor ofIndian Business and Enterprise, which was endowed by theGovernment of India, and is Director of the Centre for India& Global Business at Judge Business School. With a passionfor understanding and promoting India’s place in shapingthe global knowledge economy, he leads an importantcomponent of the University’s long-standing partnershipwith India.

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foRthComing eventS

Join us for the UK’s largest free sciencefestival, exploring subjects from astronomyto zoology, with demonstrations, hands-on experiments, talks from leadingscientists, and visits to University andpartner facilities. over 180 events will beon offer, designed to give families, adultsand children hands-on science and insightinto the University’s cutting-edge scientificresearch. many of the activities,demonstrations and children’s lectures will

take place on Science on Saturdays (13 and 20 march).

the theme will be ‘Diverse Science’ tocelebrate the international year ofBiodiversity in 2010. there will be manyopportunities to delve into diversity atevents for all ages during our family fundays and adult evening lecture series.highlights for adults include lectures byProfessor David Spiegelhalter (the WintonProfessor of the Public Understanding of

Risk) and a panel discussion entitled ‘Whatprice nature’ organised in conjunction withthe Cambridge Conservation initiative.highlights for children include an hour ofexplosive demonstrations with the nakedScientists, and a food factory Workshop –where you’re the chef with the medicalResearch Council human nutritionResearch Unit. the full programme isavailable from www.cambridgescience.org/from January 2010.

the Cambridge Cancer Centre (CCC)Symposium is a one-day eventhighlighting the interdisciplinary andcollaborative cancer research beingcarried out in Cambridge. this is thefourth CCC Symposium to take place.

talks from invited speakers and fromrecipients of CCC pilot project funding

in 2009 will showcase the latestinterdisciplinary cancer researchundertaken in Cambridge. there will be aKeynote Lecture by Professor marianoBarbacid of the Centro nacional deinvestigaciones oncológicas in madrid.the day will have ample opportunity fornetworking during the poster session and

barbecue, with delegates from Universitydepartments, institutes and local biotechcompanies. the full programme will beavailable in spring 2010 and registrationwill open shortly after this time on theCCC website (www.cancer.cam.ac.uk/).for more information, please emailkatrien.vanlook@cancer. org.uk

8–21 March 2010Cambridge Science Festival: ‘Diverse Science’

Forthcoming events: Save the dates!

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25 June 2010Cambridge Cancer Centre SymposiumCancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge

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