50 years of biochemistry - university of bristol · 50 years of biochemistry. b ristol biochemistry...

CELEBRATING 50 YEARS OF THE SCHOOL OF BIOCHEMISTRY AT THE UNIVERSITY OF BRISTOL

bristol.ac.uk/biochemistry2014

50 years of Biochemistry

Bristol Biochemistry is 50 years old. Initially taught as an offshoot of the Chemistry programmes at the University of Bristol,

Biochemistry emerged as a separate discipline in April 1964 when Senate approved the establishment of a new Department of Biochemistry. The first undergraduate intake arrived in October 1964. Initially under the leadership of Phillip Randle, and subsequently Brian Chappell, the Department grew rapidly. It quickly established an impressive international reputation that remains to this day.

Over the past 50 years Bristol Biochemistry has produced an extremely talented series of graduates who have gone on to excel in their varied careers – as Colworth Medal holders, Fellows of the Royal Society, respected world leaders in their fields of research, of prestigious academic institutions, businesses and corporations, and even a rock star. All of this has been achieved through culturing an innate interest in the fundamental study of the molecular processes that underlie life itself. The Bristol flavour of biochemistry has always been rigorous, quantitative, and with a strong molecular focus. These demanding, but successful, approaches continue to dominate both our research and our teaching programmes.

In preparing to celebrate 50 successful years of Biochemistry at Bristol we have become increasingly aware of the paucity of records for much of our history. This celebratory volume attempts to partially redress this gap. In the following pages we have articles describing the history and achievements of Bristol Biochemistry. We invite you to meet some of the people that have made Biochemistry at Bristol special – there are interviews and reminisces with many of our past staff and students and photos, old and new. This informal volume attempts to record and identify our successes over the first 50 years and also forms an introduction to our 50th anniversary celebrations to be held in September 2014.

We hope you find this celebratory volume interesting, informative and enjoyable. Perhaps it will also inspire the biochemists of the future to join us for undergraduate or graduate study, or as part of our vibrant and enthusiastic research community. We look forward to another 50 years of bringing molecules to life.

Leo BradyHead of School 2009-2014

Foreword

50 Years of Biochemistry at Bristol 1

Biochemistry 50th Anniversary

CommitteeLeo Brady Steve HalfordTom PodestaCara RichardsCaroline McKinnon

ContactSchool of BiochemistryUniversity of BristolMedical Sciences BuildingUniversity WalkBristol BS8 1TD+44 (0)117 33 12167bristol.ac.uk/biochemistryFollow us on Twitter @BristolBiochem

Thanks toDick DentonAndrew HalestrapGus CameronEmily CoyteBeth WardDavid YatesJon LaneAsh ToyeIan CollinsonAll our interviewees

Designcw-design.co.uk

PrintPrint Services, University of Bristol

© University of Bristol 2014

2 A brief history of Biochemistry at Bristol

6 Bristol Biochemists

Interviewswithsomeofthestaffandstudentswho,overtheyears,havecalledBristolBiochemistryhome.HilaryCross 6

ChrisProud 8

DavidYates 10

JordanRaff 12

PeterHenderson 14

JanDenton 16

DickDenton 18

TobyMurcott 22

GuyRutter 24

HilaryMuirhead 26

JoeYeeles 28

PatienceBarrow 30

NigelEdgell 32

SteveHalford 34

20 Gallery: now and then Imagesfromhalf-a-century

ofBiochemistryatBristol.

36 Biochemistry at Bristol, past and present

Someofthekeyscientificfindingsandresearchfromthepast50years,andalsosomeofthecurrentareasofwork.

TheBristolDNAdoublehelix 36

Theregulationofmetabolism 38

StructuralBiologyatBristol:abriefhistory 40

Mitochondria,bioenergeticsandmetabolitetransport 42

SomecurrentareasofworkinBristol Biochemistry 44

Researchonnucleicacids 46

48 The future of the Department

Contents

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36

20

48

TheMedicalSchoolbuildinghadbeenplannedbeforethewar,butconstructiondidnot

startuntiltheearly-1960swithStage1,theWestWing,completedby1964.Biochemistrywasincludedinthe1962researchcompendium,withprojectsofferedinBotany,Zoology,Chemistry,andPhysiology.IftheUniversityhadaresearchentryitneededaDepartment;in1963,whenthenewMedicalSchoolwasofficiallyopened,aChairinBiochemistrywasadvertised.

InApril1964PhilipRandlewasappointedasthefirstProfessorofBiochemistryattheUniversityofBristol.ComingfromCambridge,ProfessorRandlerecruitedanumberofhiscolleagues,includingDrBrianChappellandDrPeterGarland,aswellashisresearchstudentswhoincludedDickYorke,DickDentonandGeorgeSchofield.Randle,ChappellandGarlandallrecruitedresearchstudentstojointheirlaboratories;theywerehousedonD-floornearthemainentranceofthenewWestWingoftheMedicalSchool.TheSchoolhadanexcellentglassblower,MalcolmFowler,andgoodmechanicalworkshops,overseenbyBobTaylor,whichallowedresearcherstodevelopspectrophotometric,fluorimetricandelectrodeassays.Thesenewmethodswereexploitedbyresearchersinbioenergeticsandmetabolism.

Theearlyyearssawrapidexpansion.TheDepartmentproducednumerouspapersfromtheirnewresearchteams,whichjustifiedRandle’sdrivetoincreasebothstaffandterritorywithintheUniversity.TheBiochemicalSocietyrecognisedearlyexcellence,awardingColworthMedals(forthemostpromisingbiochemistundertheageof35)toChappellin1965,andthenGarlandin1968.In1966theRandlelaboratoryrelocatedtothe

newEastwing,asdidtheChappellgroup.SubsequentlyGarland’sgroupexpandedintotheexistingRandleterritorynearthemainentrance.Plantbiochemists,DrOwenJonesandDrTrevorGriffiths,joinedtheDepartmentandDrHerbert(Freddie)GutfreundwasrecruitedtostrengthenPhysicalBiochemistryandMolecularEnzymology.AlthoughnotcomingstraightfromCambridgehishistoryaddedtotheCantabinfluence.HeinturncatalysedtheappointmentofDrHermanWatsonandDrHilaryMuirheadtosetupX-raycrystallographicstudies.AsChemistrymovedoutoftheInnerCourt,BiochemistrymovedinandextralaboratoryspacewasalsofoundinthebasementoftheBiologyBuilding,whereDrJohnHolbrookandDrMikeTannerjoinedourstaffthere.TheInnerCourtsuiteoflaboratorieswasrenamedtheMolecularEnzymologyLaboratory,andthecoffeeroombecameadynamicdiscussionforum.BristolwasrecognisedagainbytheBiochemicalSocietyin1974whenDavidTrenthamwasawardedtheColworthMedalforhisstudiesonrapidkineticsoftheS1subfragmentofmyosin.Alittlelater,Croftsmastermindedtheinstallationofanelectronmicroscopesuite,trainingAlanBrittontoofferthisservice.WatsonandMuirheadinstalledaPDP8computertoprocessX-raycrystallographicdata,builthugemodelsandtrainedagenerationofresearchstudentsinPhysicalBiochemistry.Muirhead,ahighlyrespectedphysicalscientist,representedtheFacultyonmanyBoardsasa,thentoorare,womaninscience.

AsPhysicalBiochemistrywasdevelopingintheMolecularEnzymologyLaboratory,athirdphaseofstructuraldevelopmentwasagreed,andbuiltin1967/68.ThenewblockwasessentiallyallBiochemistry,with

adedicatedteachinglabonthetopfloor,andusewassplitbetweenDentists,MedicalBiochemistryandPharmacology.ThedevelopmentalsohousedthenewlyconstitutedMRC-funded,RegulationinMetabolism,unit.Bythemid-1970sBiochemistryhadgrowntobethemostresearch-activedepartmentintheMedicalSchool,andsubsequentrestructuringconcentratedonbringinggroupswithsimilarorcomplementaryresearchintocloseproximity.

WhilstmanystaffinBiochemistryreceivedaccoladeswhichresultedinpromotionwithintheDepartment,severalstaffmemberswerepromotedtochairsoutsideBristol.In1970GarlandwasappointedtotheChairinBiochemistryatDundee.DrPatienceBarrowwasappointedtoassistwiththeincreasingadministrativeloadontheretirementofAshfordin1973,andtookresponsibilityforundergraduateandpostgraduateadmissions.In1975RandlemovedtoaChairinOxfordandChappellwasappointedtoHeadofDepartment,apositionhewouldretainuntilhisretirementin1995.AnotherpromotionsawPhelpsmovetoheadtheDepartmentatLancaster.Followingthesedepartures,NigelBrown,SteveHalfordandAndrewHalestrapwereappointedaslecturers.In1977DavidTrenthamwasappointedtoaChairinPhiladelphia,similarlyin1978DrTonyCroftsmovedtoBiophysicsattheUniversityofUrbana,Illinois.TherecentlyvacatedspaceallowedGutfreundtomovetotheMedicalSchool,andtheInnerCourttoptwofloorsallowedHalford,Brown,andthenewlyappointedDrWoodtosetupthere.HolbrookmovedtothesharedlaboratoryonC-flooroftheMedicalSchool,andbuiltatemporarywall(himself,withhelpfromworkersfromhisfarm)acrossthelaboratorysoPharmacologycouldcontinue

A brief history of Biochemistry at Bristol

In 1960, the University of Bristol offered research in Biological Chemistry, supported by professors and lecturers from Botany, Zoology, Physiology,

Chemistry and Pharmacology.

University of Bristol2

tousetheirspace.ThesemovesconsolidatedresearchinthefieldofDNAenzymology.

Newbloodlectureshipswereannouncedin1983,andBiochemistrydecidedtodevelopexpertiseintheemergingfieldofmoleculargenetics.DrLenHallandDrBillChiawereappointed,andA100wasconvertedtoprovidetherequiredlevelofsafetyforworkingwithgeneticallymodifiedorganisms.BythistimeHolbrookwasprogressinginthefieldofsitedirectedmutagenesis,soworkingin

acommonlaboratoryblockwithHallwasnecessary.ThroughoutthisperiodM101continuedtobeapowerhouseofmetabolicresearch.TheMetabolicBiochemistrylaboratoryprovidedsomeimportantlinkswiththeDepartmentofMedicine,andthewashing-uproomwasadiscussioncentreformanyyears,beforesafetyinterestsrequiredaseparateroom.

AbiginitiativebyHolbrookin1986/7broughttogetherbothbiochemistsandchemiststobidforaMolecularRecognitionCentre,fundedbytheBBSRC.Thisprovidedposts,instrumentationandmoneytomovetheX-rayfacilitiesfromtheInnerCourttotheMedicalSchool.NewequipmentwasinstalledinChemistry,andtheSouthWestFacilityforMolecularRecognitionwasestablished,formingavaluablelinkwithorganicchemistry.Theinitialgrantwasrenewedtoprovideafurtherfiveyearsoffunding,beforetheDepartmenttookoverresponsibilityforthisfacility.Aroundthistime,WatsontookearlyretirementandwasreplacedbyLeoBrady,and

structuralbiologyexpertisewasfurtherstrengthenedbytheappointmentsofChrisDempsey,in1991,andAndreaHadfield,in1999.

WhilstRandlehadbeenthearchitectoftheexpansioninthe1960sand1970s,ChappellsteeredtheDepartmentthroughseveralroundsofausterityinthe1980sand1990stoemergeasaDepartmentthatgainedatopratingintheResearchAssessmentExercise.In1995DentonbecameHeadofDepartmentandoverthenextfiveyearsfundsforresearchanddevelopment

becamemorereadilyavailable.Thiswaspartlyduetoanimpressiverecordofgrantachievementandalsobecauseofourgoodperformanceinthenationalresearchassessmentexercise,whenourgoodratingsuppliedagenerousmultiplieronourUGCblockgrant.

TheWoolfsonBioimagingFacilitywasopenedin1997bringingtogethermanyresearchersinthefieldofcellularbiology.Itwasthefirstofanumberofsuccessfulbidsinvolvingcollaborationwithotherdepartments,andProfessorTavaré,ProfessorCullenandDrRutterquicklybecamemajorinvestigatorsusingthefacility,managedbyDrMarkJepson.

FromitsinceptionBiochemistryfollowedaCambridgemodelofteaching,whereaprogrammeoflecturesandpracticalclasseswasreinforcedbysmallgrouptutorials.Chemistrywasalwaysamandatorypartofourcourse,andthoughdislikedbymanystudents,wasverypopularwithsubsequentemployersandassistedthequantitativenatureof

thecourse.ThegeneralBiochemistrycourse(1G)inthefirstyearformedtheentrytoourprogrammeandwastakenbyallstudents.However,asstudentnumbersincreasedeventhelargestlecturetheatreinChemistrywastoosmalltohousethiscourse,sotailoredcoursesweredevelopedfortheMedicalandVeterinarystudents.Theseweremappedmoredirectlyontotheteachingneedsoftheappropriatestudents,andallowedBiochemistry1Gtocontinuewithitsexperimentalandquantitativetreatmentofscience.StudentnumbersgrewfromaBiochemistryintakeofsevenHonoursstudentsin1964,throughanintaketargetof40in1985,toourcurrentintakeofnearly100studentscomprisingbothhomeandoverseasstudents.

EarlydayssawScience,Medical,DentalandVeterinarystudentstakingfirstyearpracticalclassesinD20.InitiallyMedicalandSciencestudentssharedthislaboratory,subsequentlywhentheoldVeterinarySchoolBuildingonParkRowwasredeveloped,vetsalsomadeuseofthefacility.Laterstill,dentalstudentswereslottedintovacantgapsintheschedule,asmedicalpracticalswerereduced.DentalBiochemistrywasrunandadministeredbyDrAnneCole,whosededicationwasexemplary,andthecoursewasstrengthenedbytheappointmentofDrHayes,whotookoverthedentalcourseuponAnne’sretirement.Final-yearHonoursstudents,bythistime,hadprojectssetbymembersofstaffandsotheirpracticalworktookplaceinresearchlaboratories.

By1970theoldfashionednatureoftheseclasses,withacookeryelementwhichincludedboilingupurine,andshakingsamplesinWarburgManometers,ledtomanycomplaintsfromstudents.RandlerespondedbyappointingDavidYatesasaspecial


Biochemistry 25th anniversary meeting in Chemistry Lecture Theatre 1 in 1989.

By the mid-1970s Biochemistry had grown to be the most research active department in the Medical School

Herman Watson with a model of yeast phosphoglycerate kinase.

David Yates, Jon Lane and Ash Toye

lecturerwiththeresponsibilityofdevelopingandimplementingnewpracticals.Garlandhaddevelopedamultipurposeteachingmachine,theSpectroPlus,marketedbyMSEScientificInstruments.Thepurchaseof32oftheseenabledmoreexcitingandreactivepracticalstobeimplemented.Studentswereencouragedtorecordpracticalresultsrapidly,usingdataandcomprehensionsheetsratherthanafullwrite-upinabook,andpracticalfileswereduplicatedandsoldtostudentssotheyallhadsimilarinstructions.Atthistimenearly25%ofallstudentsenrolledintheUniversityattendedpracticalclassesinD20.From1980to1998approximately350studentsaweekattendedpracticalclassesinD20,beforeenlargedlaboratoriesweredevelopedintheEastWingofChemistry.

Overtime,newundergraduatecourseswereaddedtoourprospectuswithBiochemistrywithStudyinIndustry,pioneeredbyHolbrook,BiochemistrywithMedicalBiochemistry,andBiochemistrywithMolecularBiology.Inthe1960sindividuallecturerstaughtsectionsofthecoursewithlittlereferencetothewhole.In1975DavidTrentham,thefirstyearco-ordinator,wasthefirstmemberofstafftoattendthewholecourseoflectures.Hisfindingsallowedthecoursetodevelopbyfillingingapsandeliminatingareasofoverlap,andadegreeofqualitycontrolwasinitiated.Studentfeedbackindicatedthattheprogrammeofstudystillhadroomforimprovementandasaresult,Biochemistrybecameoneofthefirstdepartmentstochallengepotentiallecturerswitharequirementtogiveanelementarylectureaspartoftheinterviewprocess.Allstudentswereofferedsmallgrouptutorials,andstaff,postdoctoralstudentsandpostgraduatestudentswereallinvolvedinteaching.Asqualitycontrol

becamestricter,studentfeedbackquestionnairesallowedtheSeniorTutor,initiallyBarrow,andlaterYates,tomonitorandassisttutorstodevelopbestpractice.

TheresultingimprovementinlecturingandtutorialshelpedtheDepartmenttoachieveamaximum24/24inthe1999QualityAssuranceaudit.Thecombinationofhighresearchratings,goodstudentfeedbackandtopQualityAuditratingssawstudentapplicationstoBiochemistrygrow,andtheA-levelscoresrequiredincreasedfromCCCin1987toAABin2005,andsubsequentlytoAAA.Anearlygraduate,whenaskedaboutherteachinginthe1960s,describedBiochemistryasacoursetobesurvived,ratherthanenjoyed.Recentgraduatesstillfindthe

programmeofstudychallengingbutveryinteresting,andthelatestsurveyplacesBristolBiochemistryamongthetopprogrammesinthecountryforstudentsatisfaction.

In1999theofficialopeningofthenewSyntheticChemistryfacilitymadespaceavailabletodevelopasuiteofteachinglaboratoriesintheformerEastWingofChemistry,allowinglargerclasssizes.TheteachinglaboratoryspacevacatedintheSchoolofMedicalScienceswasrestructuredwiththeaidofaverylargegrantfromtheWellcomeFoundation,bidforbyDentonwithrepresentativesfromAnatomy,PhysiologyandPharmacology,andthefivefloorsconcernedwereconvertedfor21stCenturyResearch.TheHenryWellcomeIntegratedSignallinglaboratorieswereformed

asamultidisciplinaryco-operative,providingresearchfacilitiesthatspandepartmentalboundaries.

Biochemistryhad,sinceitsinception,beenpartofboththeFacultiesofScienceandofMedicinewithrepresentativesontheBoardsofeachFaculty.HonoursstudentsprogressedthroughScience,towhichourfinanceswerelinked,whilstmanystaffpromotionsandappointmentswereprogressedthroughMedicine.In1997HolbrookwasapproachedtotakeovertheroleofDeanoftheFacultyofMedicine,apostthatheretaineduntil2000.TheScienceFacultywasseenasbeingtoobig,andtheMedicalFaculty,alsolarge,hadacomplicatedadministrationduetoinvolvementwiththeNHS.TheDepartmentofVeterinary

Sciencedidnotfitwellintoeither.AnewFacultywasthereforeformed,namelytheFacultyofMedicalandVeterinaryScience.ProfessorDentonacceptedthechallengeofestablishingthis,in2003,andmovedofficesandstaffintoquartersoccupied36yearspreviouslybyProfessorRandle–Biochemistryhadcomefullcircle.ProfessorHallreplacedDentonasHeadofDepartmentand,in2004,becameDeanoftheFacultywithProfessorBantingreplacinghimasHeadofDepartment.In2009ProfessorLeoBradywaspromotedtothepostandin2013BantingbecameDeanoftheFaculty,thethirdbiochemisttoholdthispostinitsfirsttenyears.

SincethebeginningofthenewmillenniumBristolBiochemistryhasundergonesignificantchange,in


responsetoexcitingadvancesinbiomedicalscienceconcurrentwitharesearchfundingsqueezethatresultedfromfinancialandstrategicpressuresinthepublicandprivatesectors.Fromtheoutsidethoughthebiggestchangeisinthename–wearenolongeraDepartment,buthavebecomeaSchool.

Overthelastdecadewehaveseensomenotablechanges.Newacademicstaffhavebeenrecruited,includingSavery,Collinson,Kuwabara,Adams,Frayne,Woolfson(jointwithChemistry),andVerkade,MartinandNobes(jointwithPhysiologyandPharmacology),aswellasHenleyandHanley(transferredfromthedisbandedDepartmentofAnatomy).Manyothers,includingMellor,Szczelkun,Stephens,Lane,Dillingham,Toye,CurnowandRacehavetakenuppositionshavingpreviouslyheldFellowshipshere.Ofthese,thejointappointmentswithSchoolswithin,andoutside,ofthefacultyareparticularlyinterestingastheyemphasisehowoutwardlookingBiochemistryhasbecome,withanimpressiveexampleofthisflexibilitydemonstratedintherecentsuccessfulapplicationforaBBSRC/EPSRCCentreforSyntheticBiology(~£13.6M),expertlyhandledbyWoolfsonandRace.Thenewlydubbed‘BrisSynBioCentre’willcontainseveralco-investigatorsfromBiochemistryalongwithcolleaguesfromtheFacultiesofScienceandEngineering.Overthisperiodwehavealsohadtowavegoodbyetoseveralvaluedmembersofstaff.ThesehaveincludedHall(whoafteractingasDeanofFMVSwasappointedProVice-Chancellorforpersonnel),Rutter(tobecomeHeadofCellBiologyatImperial),Tanner,Halford(Emeritus),Denton(Emeritus),Booth(tobecomeHeadofChemistryatKings),Rivett,McGiven,HendersonandHadfield.

TokeepupwiththechangingdynamicoftheSchool,andtocontinuetoprovideoutstandingresearchfacilitiesfortheSchoolandwiderUniversity,therehavebeenmultiplerefurbishmentsandexpansionstoourresearchspace.Theformerteachingandresearchlaboratories,thatcomprise2.4,A-floor,A103,B-floor,andM-floor,haveseenperhapsthemostsignificantchangeswithrefurbishmentstoallbutB-floorcarriedoutprimarilywiththesupportofJointInfrastructure(JIF)grantsandtheWolfsonfoundation.MostrecentlytheBiochemistrylaboratoryspaceonD-floor(D28,D35)wasconvertedintoofficesfortheDeanandforthenewlyinstalledFacultysupportteams(Finance,HRandFacultyGraduateSchool).InreturntheSchool

obtainedspaceonC-floor,whichhadpreviouslybeensplitbetweensocialandadministrativeprovisionformedicalstudents,andwasrefurbishedin2012withtheaidoffinancialsupportfromtheUniversityandtheWolfsonFoundation.Thesecellbiologylabs(C50)provideausefulgeographiclinkbetweentheISLCellBiologylaboratoriesofAdams,CullenandTavaré,andthePhysicalBiochemistrylaboratoriesofBrady,Race,andAnderson.TheywereoriginallyoccupiedbyBanting,StephensandLane,butwithBantingtakingupthepostofDean,MellorandBassmovedinduringthesummerof2013.

TheC50labsarelocatedclosetothe‘jewelinthecrown’ofthefaculty,theWolfsonBioimagingFacility,whererecentyearshaveseenexcitingchangesnotablyalargeexpansion,in2009,makingBristolaninternationalleaderintheemergingtechniqueofcorrelativelightandelectronmicroscopy(CLEM).WiththisexpansioncametheappointmentofVerkade,anexpertintheCLEMtechnique,andthroughtheawardofalargeBBSRCequipmentgrant(Stephens)thefacilityisextendingitsCLEMcapabilitiesandcapacity.Withnewequipmentarrivingsoon,andongoingimprovementsandexpansionstotheFacultyproteomicsfacility,wewillbeabletocarryouttime-resolvedproteomicsanalysisofcomplexcellbiologicalprocessesforthefirsttime.

ThecontentanddeliveryoftheBiochemistryprogrammeshavecontinuedtoevolve,withasignificantdevelopmentbeingtheintroductionofeBioLabsasaplatformfordeliveryofmaterialssupportingpracticalsandtutorials,submissionandmarkingoflabreportsandtutormonitoringofmarksandabsences.Thelecturecontenthasundergonesignificantrevisiontoreflectchangesinbiochemistryinthe21stcentury,butstillretainingastrongemphasisondatahandlingandscientificwriting.Inthelatestdevelopmentteachingofbiologicalchemistryisfinallytobebroughtin-housethroughthecreationoftwofirst-yearunitstositalongsidegeneralBiochemistry.ThiswillbetterintegrateBiologicalChemistry,BiophysicsandBioenergeticsintoastrongerfoundationforthelateryearsofthedegreeprogrammes.

WehavealsointroducedtaughtpostgraduateprogrammesinBiomedicalScienceandResearchandBiophysicsandMolecularLifeScienceswhichareattractivetooverseasstudentsaswellasourowngraduates.

Onits50thanniversaryBiochemistrycantrulybeconsideredasacross-faculty,interdisciplinarylinchpinofresearchandteachinginBristol.Itveryeffectivelyspanstopicsfromthemolecular(suchaschemicalreactionsandinteractionsthattakeplacewithinandbetweenproteins),throughthemacromolecularlevel,totopicscoveringthefarlargerscaleofthedynamicinteractionstakingplacebetweencellsintissuesandwholeorganisms.Inthisway,researchinterestsinBiochemistryleantowardsbothphysicalandmedicalsciencedisciplines–animpressivefeatgiventherelativelysmallsizeoftheSchool.Thishasbeenachievedthroughimportantnewappointments,includingjointappointments,acrossdepartmentsandfaculties,throughstrategicrecruitmentofnewResearchFellows,andtheimpressiveongoingexpansionofcoreresearchfacilities–anendeavourthathasbeenessentialinrecruitingnewstaffandmaintainingourresearchcompetitiveness.Notonlyisthisbroadeningofscopereflectedinourcurrentresearch,butitalsoinfluencesthelearningexperiencecontainedwithinourteachingprogrammesandthecareerchoicesthatBristolBiochemistrygraduatesmake.

Inthesummerof2014LeoBradywillbesteppingdownasHeadofSchoolandKateNobeswilltakeuptherole.Shewillbetakingthehelmofatightly-runshipwithawellfundedandsupportedbroadresearchbase,excellentteaching,andgreatpossibilitiesforexpansioninthefuture.

Undergraduate practicals in A89, Biological Sciences Building.

A big initiative by Holbrook brought together biochemists and chemists to bid for a Molecular Recognition Centre

Corrine Smith in the early molecular graphics room.

Molecular enzymology in the 1970s, including Mike Geeves, John Eccleston, David Yates, Freddie Gutfreund, Martin Webb, Paul Attwood, David Trentham and Steve Halford.


Q What was your role at the University of Bristol?

A MyrolewasasaTeachingLaboratoryTechnicianintheYear1teachinglaboratory.Iinteractedwithagreatnumberofstudents(HonoursBiochemistry,othersubjectHonours,dentists,vetsandmedics).Ipreparedthepracticalclasses,soI’dbeverybusyduringterm-time.Eachweek,eachclasswasdifferent.Itendedtobemakingsolutionsandtryingouttheexperiments.Outofterm-timeIwouldhelpsortoutexamscriptsandmarks,andtryoutnewpracticalclassexperiments.

Q What brought you to the University?

A IamaBristolianandattendedAshtonParkSchool.IwasalwaysinterestedinscienceandwantedtoworkinalabsowhenIwasintheSixthFormIappliedforvariouslocaljobs.IwasfortunatetohaveaninterviewwithCharlesAshfordintheBiochemistryDepartmentandgotthejobasajuniortechnician.IwasveryluckytostartwhenIdid.Idon’tthinkthattheDepartmenttookonmanymorejuniortechnicians(certainlynottwoonthesameday!).

Interview with…

Hilary Cross


Q Can you remember your first day?

A NigelEdgellwasinterviewedonthesamedayasmeandhetoogotajobasajuniortechnician.HeandIwenttoprimaryandsecondaryschooltogetherandwestartedatBristolUniversityonthesameday.IremembermeetinginthefoyeroftheMedicalSchoolBuilding–IwentfirsttoroomD20whichwasoneoftheYear1labsandIstartedworkstraightaway.Therewerenointroductorydaysoranythinglikethat,backthen.IstartedwithYvonneWilliamsandLesCorbinwhoweretheteachinglabtechniciansatthetime,andtheyshowedmewhattodo.Itwasoutoftermsotheyweren’ttoobusyandIhadalittlewhiletolearnonthejobbeforethetermandclassesstartedinearlyOctober.

AcoupleofmonthslaterImovedtoA100labandsetupthepracticalclassesforthedentalstudents,withDrAnneCole,andlateralsotheYear2students,withMollieLuscombe.Theninthemid-1980sthedentistsmovedtotheYear1labandtheYear1students,dentists,medicsandvets,allusedthesamelab.

Q Why do you think Biochemistry at Bristol is so highly regarded?

A Thedepartmenthadaverygoodfoundation,withProfessorPhilipRandle,attheverybeginning.TheDepartmenthasalwaysbeenverypioneeringandattheforefrontofresearch.ThisattractsthebestpeopleandsotheDepartment’sreputationincreasesandbecomesinternational.

Q Can you name any significant changes which took place while you worked at Bristol?

A TheSchoolnowhasmoreup-to-date,state-of-the-artlabsandequipment.Fromatechnician’spointofview,therearealotmorestudentsandfewertechniciansthanbefore.Ithinkthateverythingwasmorepersonalinthosedays–eachlabgrouphadtheirowntechnician.

Q Why do you think there are not many women in Biochemistry?

A Beingatechnician,ie.supportstaff,therehavealwaysbeenmorewomensupportstaffsoIdidn’tnoticethedifferencesomuch.IagreethattherewerenotagreatdealofwomenacademicstaffwhenIfirststarted.ButIthinkthiswasgeneralformostprofessionsandacademicsinyearsgoneby.Inthosedayswomentendedtochoosebetweenacareerorgettingmarriedandhavingchildren.Nowmorewomenaregoingtouniversity,takingPhDsandmanywomencombinebothcareerandhavingafamily.

WhenIfirststartedIwasworkingwithAnneCole,MollieLuscombe,HilaryMuirheadandPatienceBarrowwhowasthedepartmentadministrator.SoIhadearlycontactwithseveralfemalemembersofacademicstaff.IrememberduringanearlySchoolsWeekoneofthevisitingteacherscommentedthattherewerenotanyfemaleacademicstafftakingorrunningtheeventandthatitwasn’tsoencouragingfortheschoolgirls.Inrecentyearstherehavebeennearlyallfemaleacademicstaffrunningeventsfortheschoolchildren.

Q Do you have a best memory from your time at Bristol?

A MybestmemoryisofbeingpresentedwithmyLongServiceAwardinrecognitionof40yearsofservicetotheUniversitybytheChancellor,BaronessHale.IttookplaceattheannualmeetingofUniversityCourtinDecember2011.NigelEdgellwaspresentedwithhisawardatthesametime.Itwasalovelyoccasion.Idon’tknowwherethose40yearswent,thetimegoesbysoquickly!IenjoyedmytimeintheBiochemistryteachinglab.IthinkthejobjustsuitedmeandBiochemistrywasalwaysagooddepartmenttoworkfor.


Hilary started her career at the University of Bristol as a junior technician in 1971. Initially Hilary spent much of her time working with Anne Cole, helping her set up and run the biochemistry course for dental students. In the 1980s Hilary moved to the main teaching lab where she prepared practicals for Year 1 groups. She became a central figure in Biochemistry, teaching within the School until her retirement in 2012.

The department has always been very pioneering and at the forefront of research. This attracts the best people

and so the department’s reputation increases and becomes

international.

Bristol Biochemists

The key to the success of the School of Biochemistry has been, and will continue to be, thanks to the people within it.

Cara Richards interviewed a selection of students and staff, past and present, to learn more about the last 50 years.We start with Hilary Cross, a lab technician,

who worked at the School for forty years.

Everyone in the lab just got on extremely well and this made it both an enjoyable place to work but also a very productive one because we worked well as a team.

I think that’s what has helped to build Bristol up, people all try and help each other and strive to be the best they possibly can, which is what you want to do but it’s not

always that easy to achieve it.

Q What brought you to the University of Bristol?

A BristolwasalreadytheleadingdepartmentforBiochemistrywhenIappliedbackin1970.Iwasinvitedtovisitandhadachancetolookaround.ThisgavemeagoodfeelforBristolasaplacetoliveandstudy.TherewasalotgoingonintheBiochemistryDepartmentandofcourseBristolisalsoanicecity.IthoughtitwasagoodplacetocometoandIwasrightbecauseIhadaveryenjoyableexperienceasastudentinBiochemistry.Indeed,itwasmytimeinBristolthatsentmeinthedirectionthattherestofmycareerhasfollowed–thelecturerstriggeredmyaspirationtocontinuewiththeparticularlineofresearchIhavefollowedeversince.IsubsequentlymovedtoScotlandformyPhD,andthenworkedasapostdocinGöttingeninGermany.InbothplacesIstudiedhowcellmetabolismiscontrolled,anditwasmyundergraduatelecturesinBristolthatfiredmyinterestininvestigatingthis.AdecadeorsolateritwasclearthatBristolwasaprimelocationtoreturntoasalecturertocontinuewiththatresearch,andIwasfortunatetoberecruitedtotheBiochemistryDepartmentatBristolasalecturer.

Q Who do you remember in particular?

A Amongthelecturerswhotaughtme,thepersonwhoprobablyhadthebiggestinfluenceonmewasDickDenton.Hegavelecturesontheemergingunderstandingofhowenzymesareregulatedbyhormones,andhowthiscontrolscellmetabolism.Iwasespeciallyinterestedinhowinsulinworks–butatthattime,wedidn’treallyknowanythingaboutthis.Somethingwasalreadyknownabouthowotherhormones,suchasadrenaline,workedanditwasDick’slecturesonthistopicthatreallyinspiredmetothinkhoweleganttheseregulatorymechanismswereandhowmuchI’dliketobeinvolvedintryingtofigureouthowinsulinworked.

InfactIinitiallywantedtodoaPhDinBristol,forexamplewithDick.However,hedidnothaveastudentshipavailable.HesuggestedItalktosomeonewhohadrecentlystartedhisownlabinDundeeandwascomingdowntoBristolfor

atalk(organisedbytheBiochemicalSociety).HisnamewasPhilipCohen.PhilipinvitedmeuptoDundeetolookaround.Itooktheovernighttrain–butcouldn’taffordthesleeperandonlyhadanhour’ssleep.Nonetheless,ImusthaveseemedrelativelywideawakeasPhilipofferedmethestudentshiphehad,soIwenttoDundeetodoaPhDwithhim.Philiphas,overmanyyears,establishedhimselfasoneoftheleadingscientistsinthisfieldworldwideandhasdevelopedanenormouslysuccessfulresearchcentreinDundee.IhavebeenfortunateinhavingDick’sinputearlyinmyuniversityeducationandthenPhilipCohen’saddedimpetus,whichtogetherpropelledmeinthedirectionwhichmycareerhassubsequentlyfollowed.

FrommytimeasanundergraduateatBristol,IalsoparticularlyrememberotherpeoplelikeJohnHolbrookandFreddieGutfreund,whointroducedmetoproteinsandenzymes.IalsovividlyrememberJohnWilliams;hehadaverydifferentlecturingstylefromalmosteverybodyelse,whogave‘formal’lectures,whilehejustsatonthebenchatthefrontandtalkedad lib,itseemed,for45-50minutesinaveryenthusiasticway.Hedidn’tusetheblackboardmuch,butkeptyourattentionsimplybecausehewasveryengaging.Itwaseffectiveandinteresting.IdidmyundergraduatepracticalprojectwithTrevorGriffithsandthatwasgreatfun.TrevorsharedhislabwithOwenJones;theyandtheirteamsweregreattoworkwith,anditwasthatexperiencewhichconvincedmethatwhatIwantedtodoaftergraduatingwastodoaPhD.

HilaryMuirhead,whosupervisedmylibraryproject,wassomeoneIalsoparticularlyliked.Shewasaveryfriendlyandapproachableperson.Shewasadelightfulpersontoworkwith,verystraightforwardandmatteroffact;shewouldjusttellyouwhatyouwantedtoknow,andcommunicatedbothinformationandenthusiasmveryeffectively.

Q Do you have a best memory?

A ImustconfessthatmybestmemoriesasanundergraduatearelesstodowiththecourseandmoretodowiththesocialsideandthefriendsImadeatthattime,almostallofwhomIamstillinregularcontactwith.Iwas

Interview with…

Chris Proud


verykeenonrockmusicatthattimeandthosewerethedayswhenbigbandsstillplayedsmallervenuessuchastheColstonHall.Famous,internationalactswouldplaythereatthattime.IwenttoseeSantana,NeilYoung,TheSmallFaces,JeffBeck,Indeedawholeloadof1970’srockacts.TheStudentUnionalsoattractedsomeprettybignamesinthosedays.IwenttoseeChickCorea,WingsandTheKinksintheSU.

Later,whenIreturnedtoBristoltorunmyownresearchgroup,IwasbasedinalabcalledM101.Ithadagreatatmosphere–metaphoricallyspeakingatleast–thephysicalatmospherewascharacterisedbyacuriousodourfromanundefinedsource.M101hassincebeenrefurbishedandthatsmellhasnowgone!OneofthegoodthingsaboutM101wastheannuallaboutingandattheretirementpartyforNigelEdgell(astalwartofM101),JeremyTavaré(andothers)haddredgedupsomereallyembarrassing,ancient,photosfromtheseoutings.Embarrassingmostlyduetopeople’shairstylesorclothes,beingthe1980sIcanprobablyleaveyoutoimagine!Inmycase,Iwasnotoriousforgettingthevenueofthelaboutingwrongtwice.Iwenttothewrongplaceandendeduphavingasoloouting.

Q Why do you think Bristol Biochemistry has such a good reputation?

A Ithinkmostofthesethingsboildowntothepeoplewhoareinvolved.Asweknowthedepartmentis50yearsoldnow,soithasalonghistory.ManyofthepioneeringpeopleinbiochemistryintheUKwereassociatedwithBristol.ManyofwhomthemhadmovedfromCambridgewhentheDepartmentwassetup,andIthinkthishelpedtocreateaverygoodhigh-achievingethosintheDepartment.Theywantedtheirundergraduatestodowell,andtheyalsowantedtobeexcellentintheirownresearch.AsImentionedalready,thelabthatmygroupwashousedinwasM101.Ithadhadagreatatmospherebecausetherewereseveralgroupsworkingtogether–DickDenton’sgroup,AndrewHalestrap’steamandthenlater,JeremyTavaré’s

lab,andmine.Everyoneinthelabgotonverywell,bothscientificallyandsocially.Thismadeitbothanenjoyableplacetoworkandalsoaveryproductiveone,becauseweworkedverywellasateam.IthinkM101typifiedformethecharacterofBristolBiochemistry–friendly,interactiveandwithhighaspirations.Andthepubsnearby,onStMichael’sHill,certainlyhelpedwithsocialising!

Q What changes took place during your time at Bristol?

A Ithinkthereweretwobigchanges.OnewasmovingresearchersupfromWoodlandRoad(MolecularEnzymology)intotheMedicalSchool.Thesecondwasthat,basedonitssuccess,theDepartmenthasgrownalottoo,hiringmanytalentednewpeopleacrossadiverserangeofareas.

Idon’tknowhowmanypeopletherewerewhenIstartedbutitwascertainlyquitesmall,andit’scertainlybiggernow.Thesubject(biochemistry)hasalsochangedsomuchinthefortyyearssinceIwasanundergraduatethere.Inthebeginningthedepartmentfocusedonafewareas,suchasbioenergetics(howcellsobtainenergyfromnutrientsand,inthecaseofplants,fromsunlight)andmetabolismandenzymes.Now,ofcourse,itcoversaverywideareaofscience.

Q What advice would you give to new students who are starting a course in biochemistry at Bristol?

A Thisisreallyadviceforsomeonethinkingintermsoftheircareeraftergraduating–whetherornotyou’repursuingacareerinresearch,youneedtofindsomethingthatyou’redeeplyinterestedin.Itcan’tbeapassing,peripheralinterest,ithastobesomethingwhichreally‘grabs’you.IhavebeenluckythatthetopicthatinterestedmeasastudentatBristol(thebiochemicalmechanismswherebyhormonescontrolthefunctionsofcells)stillcontinuestofascinatemeandformsthebasisofmyresearchtoday.


Chris studied Biochemistry at Bristol as an undergraduate from 1971-74. He studied for his PhD at the University of Dundee, then returned to Bristol as a lecturer and reader from 1985-95. He also worked at the University of Dundee, the University of British Columbia and the University of Kent. He is now based at the University of Southampton where he is professor of cellular regulation.

Q What were the early days at Bristol like?

A IhavemanyhappymemoriesofmyyearsasaPhDstudent.ItwasatimewhenpracticaljokeswerecommonandveryoftenthesewereattheexpenseofHealthandSafety.Inthelate1960stoearly70swhenProfessorSirPhilipRandleusedtodomanytestsonrats,inordertorendertheratsunconscious,ether-soakedpapertowelswouldbeaddedtotheglasstanksinwhichtheratswerekept.Thepapertowelsweresubsequentlythrownintoawastepaperbin.Oneday,whenRandlereturnedtohislaboratoryhepromptlyemptiedhispipeintothebin,causingalargefiretoerupt.Randle’sonlywordswere‘Ah!Ether’.PhilipRandle’snotoriousloveofresearchonratswascelebratedwhentheDepartmenthaditssilveranniversarywithacommemorativecakeintheshapeofalargepinkrat,whichheceremoniallybeheaded!

ProfessorSirPhilipRandlefeaturesgreatlyinDavidYates’anecdotesfromhisearlytimeatBristol.Hedescribesthemanindetail,alargemaninheightandbuild,whousedtoswiminthepoolinthebasementoftheStudentUnion.AccordingtoYates,hewouldstandatthedeepend,atthesix-footmarker,andindoingsohisheadandshoulderswouldbeabovethesurface.OthermembersofstaffwouldseethepoolasaprimelocationtoinitiateorcontinuetheirconversationsaboutDepartmentalaffairs,butduetotheextremeheightdifferencewouldbeforcedtoconducttheirbusiness,atthedeepend,swimmingincirclesaroundRandle.

Q What did you find most enjoyable during your time in Biochemistry?

A Myfavouritethingwasinteractingwithstudents.AftertheretirementofPatienceBarrow,IwasaskedtotakeoverasAdmissionsTutor;thiswasajobIrelished,andheldfor18years.Duringthistime,Iwouldvisitneighbouringschoolsandvisitcareersfairs.Thisreallyhelpedtogivemeanunderstandingofwhatstudentswantedandthequestionstheyneededanswering.IalsorememberhavingtogiveanannualspeechtoourstudentseveryChristmastime,warningthemoftheneedtoreviseinthehopethiswouldshockthemintoaction.

Q What brought you to the University of Bristol? A Iwasrecruited,andenticed,bytheeminentreputationofSirPhilipRandleandPeterGarland,whohadtutoredmeatCambridge.Iwasnottobedisappointed.

Q What single thing would you say defines Biochemistry at Bristol?

A Bristolhasastrongcommitmenttoacademicrigour.TheBiochemistryprogrammehasalwayshadastrongchemicalandmolecularflavour,includingplentifulimmersioninquantitativemethods.Itisconsideredchallengingbyourstudentsandstrongtrainingbytheirprospectiveemployers.

Interview with…

David Yates


Q Why do you think Bristol Biochemistry is so highly regarded?

A BiochemistryresearchatBristolhasalwaysbeenworld-leading.Inaddition,thebiochemistryteachingprogrammeincreasinglybecameapriorityforourstaff.Myappointmentwasinstigatedbyaneedtorevitaliseteachingpracticalsandtointroducenewideastotheteachingprogramme.InanefforttoinstigatechangeinBristol’spracticalteachingprotocol,Iwouldwritetootherinstitutionsofferinganexchangeofideas.ThisledtomebeingaskedbytheBiochemicalSocietytorunagroupfocusingonpracticalteaching.

TheDepartmentcontinuedwiththiscommitmenttoprovideexcellentteaching,bylaterchangingtheprocedurebywhichnewmembersoflecturingstaffwereappointed.Initiallynewmembersofstaffwereselectedsolelybasedupontheirresearchprowess,howeveranewinterviewprotocolwasimplemented,aspartoftheinterviewprocess,thatrequirednewmembersofstafftoprovethemselvesbygivingasamplelectureataleveltoengagefirst-yearstudents.Thisupped the anteforlecturersandservedtodemonstratethedesire,inBiochemistry,toprovidefirst-classteachingforourundergraduates.

Q What has changed since your time at Bristol?

A OfcourseHealthandSafetyrequirementshavebecomeincreasinglyonerous.Thisseemstohavetakenmuchofthefunoutofresearch.Inaddition,intheearlydaysacademicswereprettymuchfreetoworkonwhateverinspiredtheirinterest.Nowgrantfundingisessentialandmorecompetitive,andthepressuretoproducegoodpublicationsisalwaysthere.Itisafarmoreseriousbusiness.

Q Most important scientific advances from Bristol Biochemistry?

A Therearetoomanytochoosefrom!TheworkofMRCMetabolismUnit;FreddieGutfreund’sworkonrapidreactionkinetics;BrianChappell’sgroundbreakingresearchonchemiosmotictransport;TonyCroft’sworkonmitochondriaandbioenergetics;JohnHolbrook’sproteinengineeringstudiesofenzymes;proteinstructuralstudiesbyHermanWatson,HilaryMuirheadand(later)LeoBrady.Bristol’sstrengthslieinmetabolicbiochemistryandbioenergetics,alongwithmoleculargenetics.

Q Were there any particular people in Biochemistry who had a big impact on you?

A FreddieGutfreundwasalwaysgoodtohistechniciansandwasadelighttoworkwith.PeterGarlandwasgenerousbutachallengetoworkfor–healwaysthoughtofthebestexperimentsfirst!BrianChappell,despitehisfearsomereputation,wasextremelyfair,excellentatadministrationandtaughtmehowtobegenerous.

Q What advice would you give to new students starting out in biochemistry at Bristol?

A Workhard,keepupwithyourlecturesandreviseregularly.


Bristol has a strong commitment to academic rigour.

David was a part of Bristol Biochemistry for more than 40 years. Arriving at Bristol University at the same time as Professor Sir Philip Randle in 1964, David was initially a PhD student with Peter Garland. He subsequently went on to become a research assistant with Freddie Gutfreund, then a lecturer, and finally senior tutor and departmental administrator, up until his retirement in 2006.

Undergraduate practical class in A89 of the Biological Sciences Building.

Q Why did you choose to study at the University of Bristol?

A Tobehonest,Iwasprobablyabitnaïve!Iwasn’taparticularlyacademicpersonatthatage,soitwasn’taveryinformedchoice.IhadheardthatBristolwasafunplacetobeandIknewthatithadaverygoodreputation.Itwasalsotherightmixofbeingfarenoughfrommyhomeatthetime(London)butnotmilesaway.IvisitedbeforeIcame,anditlookedlikealovelycitytolivein.ItwastopofmylistandIjustscrapedinwiththreeBs.

Q What made you choose to study biochemistry?

A ItwasprobablythethingthatIwasleastbadat.IreallylikedscienceandifIcouldhaveIwouldhavestudiedphysicsbutIwasn’tgoodenoughatmaths.PhysicswaswhatIfoundmostinteresting.Asforbiology,Ihadn’tstudieditatA-levelbutIhadfriendswhodidanditjustsoundedlike

somuchlearning.PlusIcouldn’tdochemistry,becauseofthemathsagain,itwouldhavebeenjustalittlebittoohard.SoIdecidedtopitchatwhatIfeltwasrightformeandbiochemistryturnedouttobethecorrectchoice.

Q How did you find the biochemistry course at Bristol?

A I’dbeinterestedtoseewhatthecourseislikenowbut,backthen,wedidn’thavealotofoptions;wehadtostudybiochemistry,chemistryandoneextra.AlotofpeoplefoundchemistryreallyeasybutIfounditreallydifficultsoinmysecondyearImadeareallygoodchoice.Ididenvironmentalchemistry.Firstly,itwaswayeasierthanchemistryandsecondly,itwasbrilliant,Ifounditreallyinteresting.Althoughitwasmoreonthebiologysideofthings,environmentalchemistrywasthebestthingIdidhere,andthemostfun.Itwasn’tuntilmyfinalyearwhenIdidalibraryprojectandthenarotationprojectinthelabthatIdecidedtobeascientist.Ireallyenjoyedbeinginthelab.


Q Why do you think Biochemistry at Bristol is so highly regarded?

A Oneofthebigadvantagesithasisitshistory.Everyoneknowsit’soneoftheclassicdepartments.Bristolhasareputationforbeingaverygoodplacetolearnandagreatplaceforresearchbutalsothecityisreallynice.SoIthinkallofthosethingscombinetomakethisoneofthetopplaceswherestudentsliketogo.BristolUniversityiscertainlystillsomewhereI’drecommendtomykids.

Q Have you noticed any changes, in coming back to Biochemistry?

A Well,givenwhoisherenowI’msurealothaschangedintermsofthecourseitself.ButIjustgavealectureandthelecturetheatrehasn’tchanged,they’vechangedtheseatsbutitlookedjustthesame.Nothingelsehaschangedanawfullot.Igraduatedin1986,nearly30yearsago,soit’sprettyamazingthatIcomebackandsomanypeoplearestillhere.Itmustbeveryhardtoleave.Forthedepartment,it’salwaysgoodtogetnewbloodinbutIthinkpeoplelikeitheresomuchtheystayherealongtime,it’sreallyremarkable.Thereisstillthatmixofoldnameswhoarestillhere,butalsoneweroneslikeDavidStephens.

Q What are your best memories of Bristol?

A ImetmywifeatBristol,sothat’sagoodone.Shewasaphysicistandmuchclevererthanme,shewasreallygoodatmaths.Meetingherwasadefinitehighlight.Inmyfinalyear,itwasthefirsttimethatdoingworkwasinterestingsoIreallyenjoyedthatlastyear.IplayedlotsoffootballonCliftonDownsandIrememberthesunsettingoverthebridge;thosearethekindsofthingsImiss.Whenweleft,afewfriendsandIwentforafinalwalkaroundtheDownsanditwasbeautifulday,thesunwassetting,itwasaprettymagicallastdayinBristol.IdefinitelyhaveveryfondmemoriesandIreallylikecomingback.

Q Have you stayed in touch with any fellow students?

A Ihaven’tkeptintouchwithverymanypeoplefromBiochemistrybutIbumpintosome,nowandagain.IstillseeEmmaLitherland,whowasinmyclass.Wehadareunionactually,onlyafewweeksago,withsevenoreightofusandwemetuponthedaywewouldhavearrived30yearsago.Emmawasthere,butalsosomepeoplefromPhysicsandpeoplewehadmetinhalls.IhadmybigCRUK(CancerResearchUK)grantrenewaltheotherday,mybigfive-yeargrant,anditbasicallyrunsthewholelab.Therewasthisguy,PaulClarke,there(who’sinDundeenow);Iknewthename,thenIsawapicture,andIthought‘IthinkIrecognisethatguy’;itturnsouthewasinthesameclassasme.HedefinitelyhasabigswayinwhetherornotIgetthegrant!Ihaven’theardyetwhetherIgotit,ornot,butwe’llsee.


A Onewhoisnolongerhere–aguycalledBillChiaandhewasn’tactuallyatBiochemistrythatlongbuthewastheonly‘fly’personandIwashungeringforthatkindofcellanddevelopmentalstuffratherthanthehard-corebiochemistry.HegaveustheonlylectureswehadonfliesandIrememberItalkedtohimquitealotwhenIwasthinkingaboutstayinginresearchandaboutwhichlabstogoto.He’sactuallyquiteabigfigureinthefield,it’sabitremovedfromwhatIdonowbutIstillbumpintohiminmeetingsandthings.IalsorememberbothAndrewHalestrap’sandSteveHalford’slecturesverywell.

Q Can you remember your first day at the University?

A It’ssearedonmymemory.ThefirstthingIcanrememberisdrivinguptheM4,withmydadandbrother,feelingverynervousandnotknowingwhatitwasgoingtobelike.Aswepulleduptothehall,mybrotherseesthisguygettingoutwiththisbigsetofgolfclubsandhesaid‘whobringsafullsetofgolfclubs?Thisisgoingtobeterrible,you’regoingtohateit!’ButthatguybecameoneofmybestfriendseventhoughIcan’tplaygolfandneverdid.It’sfunnythatthepeopleImetonthosefirstdayswerethepeopleIendeduphangingoutwith.It’squitestrange,you’rejustthrowntogetherreally.Wealsostartedworkinginthefirstweekanditwasabitstressfulinthebeginning,butwesurvived.


Interview with…

Jordan RaffJordan studied for his BSc in Biochemistry at Bristol from 1983-86. He then completed his PhD at Imperial College London; his work focused on cell division in fruit flies. He has continued in this field throughout his scientific career working as a postdoctoral fellow at the University of California, San Francisco, and then as a, Wellcome Trust funded, Senior Research Fellow at the Cancer Research UK Institute in Cambridge. Jordan has since relocated to Oxford and runs a lab, backed by Cancer Research UK, based in the Dunn School of Pathology.

I graduated in 1986, nearly 30 years ago,

so it’s pretty amazing that I come back and

so many people are still here. It must be very

hard to leave.

Bristol has a reputation for being a

very good place to learn and a great place for

research but also the city is really nice.

forpublication.Therewerepublicationsfromtheothersatthattimetoo.Inretrospectwewereverysuccessful,butinaratherinformalway.

Q What were your interests outside of the lab?

A TheundergraduateBiochemists(initiallyonlynineofus)wouldcertainlymeetupandgooutforlunchofapieandahalfofbitter.IplayedrugbyfortheChurchillsecondteam.IparticularlyremembergoingtotheVictoriaRoomsfortheSaturdaynightdances.Therewasabarthereandlocalrockgroupswouldbeplaying–IrememberonecalledJohnnySladeandtheVikings.Busloadsofgirlswouldcomeinfromtheteachingcollegesandthatwaswheresomeofmygroupmettheirsubsequentpartners.ItwasthetimeoftheBeatlesandtheStonesandwe’dhavearoundofpartiesattheweekend–IrememberoneinaquarryintheAvonGorge.

Q Do you have a best memory of Bristol?

A IwasinBristolforjustoversixyearsaltogether,sotherearelotsofgoodmemories.ForexampleImetmywifethere(inapubcalledtheAlbion),andImadesomeverygoodfriendsatUniversity.Ienjoyedmyfirstyearfartoomuch;IreceivedaDean’sletterattheendofit,whichwasakindofwarning.IthinkpartoftheproblemwasIcamefromasingle-sexschoolandwasveryimmature,andhavinggirlsaroundwasabigthing.Itsoundsverynaïvecomparedtotoday.Isettleddowninmysecondandthirdyears.

Q Why do you think Bristol has such a good reputation for biochemistry?

A Istudiedphysiologyandchemistryfortwoyears.Thenweweresoluckythat,forourthirdyear,PhilipRandlebecamethefirstProfessorofbiochemistryandbroughtinBrianChappellandPeterGarlandandwewerethefirstfinalyeartheytaught.Therewerebythenonlysixofus.Weheardaboutfrontlinemetabolic

biochemistryforayearanditwasfantastic.IthinkBristolBiochemistrygrewveryrapidlyinreputation,theequalofOxbridgeinmanypeople’seyes.

PhilipandsubsequentDepartmentheadslikeBrianweresuccessfulinrecruitingverygoodresearchers,andtheDepartmentgrewandgrew.Theyallsetveryhighresearchandteachingstandardswithouteventhinkingaboutit.Thatwasaveryreallegacy.

Q What do you think of the city of Bristol?

A EveryoneIknowwholivedinBristol,likedit.WhenIwasastudentCliftonwasveryrundown;itwaswherealltheawfulstudentflatswereandwheremanyofuslivedandwherethepartieswentonatweekends.IdearlywishI’dhadenoughmoneytobuyanapartmentinCliftonbackthen.Westillvisitrelativesandfriendsthereregularly.

Q What did you do when you left Bristol?

A MywifeandIwenttoMadison,WisconsinintheUSAafterIfinishedmyPhDandwewerethereforthreeyears.IdidpostdoctoralresearchontheeffectsofantibioticsattheEnzymeInstituteunderHenryLardy.ItwasduringadifficulttimeintheStatesbecausetheuniversitieswereattheforefrontoftheanti-Vietnamwardemonstrations.ThiswasthetimeoftheKentStateshootingsinwhichfourstudentswereshotdeadbytheOhioNationalGuardduringananti-wardemonstration.WeactuallyhadtheNationalGuardontheMadisonCampus;theycarriedloadedgunsandwedidgetassociatedwithone

demonstrationthatinvolvedseveralthousandsofpeople.Asitmovedaroundthecorneranduptowardsthecapitolbuilding,wefoundourselvesfairlynearthefrontandwerealisedthattherewasalineaheadofNationalGuardswithfixedbayonets.Wouldyoubelieveit?AmericansagainstAmericans.Whatsavedthedaywasthatthepeoplepeeledoffintothestreetsoneitherside.WestillhaveaphotooftheFBIphotographingus.WereturnedtotheUKwhereIworkedwithHansKornbergatLeicesterandCambridge.

Q What advice would you give to biochemistry students today?

A Itwaspossibleforus,attheendoftheundergraduatethreeyears,tofeelwehadmasteredmostofbiochemistry;Ithinkitwouldbeprettyimpossibleinthesepost-genomedaysforanybodytofeelthat.Choosingaspecialitysubjecttostudyisthereforeamuchmorecriticalaspectofone’scareertodaythanitwasthen.Theotherfactoristhatemployabilityismoredifficulttoachievenow.Itmustbeaggravatingtotheyoungergenerations,butwegavelittlethoughttowhowasgoingtoemployus.AcademicjobswereperfectlypossibleandindustrieswouldactuallycometotheUniversitiestorecruitpeoplewhereasnowtheysiftthroughthousandsofapplicationsforfarfewerposts.

Theclimateisverydifferentnow.Frommyexperiencemyadvice,totoday’sstudents,isthatarigorousbiochemicaltrainingenablesyoutounderstandmostotherbiologicalandbiomedicaldisciplines,creatingmanycareeroptions,butthenIwouldsaythatwouldn’tI?!

Q Why did you choose to study biochemistry?

A AtschoolIwasveryinterestedinbiology.AllIknewwasthatIdidn’twanttodotheusualmedicineorveterinarysciences.Ifoundabookthathadsomebiologicalchemistryinit,glycolysisandtheKrebscycle,andIthought,wellmaybehereisaninterestingopportunity.Atparents’evenings,thechemistrymasteradvisedonuniversitiestochooseandIremembermymothersaying‘hethinksBristol’sagoodoption’soIwenttoaninterviewandgotin.

Q Can you remember your first week at Bristol?

A ItwasmostlycentredaroundChurchillHall.ThefirstpeoplewhoalsoarrivedonmystaircasewereallGeordiesandIcouldnotunderstandawordtheysaid!SoitseemedalittlestrangetoasouthernerfromPortsmouth.IhadaveryoldbicyclethatIusedtogettotheDepartment,cyclingdownWhiteladiesRoad.Itwasamatterofhonourtocycleallthewaybackuptothetop.Thephysiologylectures,givenbytheprofessor,wereextremelystrict;hewouldlockthedoorsonobodycouldcomeinlate.

Irememberthepracticalclassesbecausetheyweresobizarre–thethingsthatwewereworkingon,frogmuscle,ourownurine,spittle,andallsortsofassays.Icanremembermessingaroundinsomeofthosephysiologypracticalclasses;infactIgotthrownoutofoneofthem.Chemistrywasverygoodandreallyhard–forexamplewehadtoundertakepracticalprojectsfromtheoriginaltextbookinGerman.

Q What research did you do at Bristol?

A IwasveryimpressedbyBrianChappell’sworkonmitochondria,andtheadvancedtechniqueshedevisedtostudythem.HetookonseveralnewPhDstudentsatthetime–BrianRobinson,RichardHansfordandmyselffromBristol,andJohnMcGivanfromCambridge.KeithHaarhoffandTonyCroftswerealreadyworkingwithBrian.MyprojectwasatfirstinvestigatingtheroleofcalciuminH+/Oratiosinmitochondria;BriansuspectedthatthecalciummovementsmightbeprimaryratherthandrivenbytheprotonmovementsasrequiredbyPeterMitchell’sChemisomoticTheory.Thiswasratheranti-MitchellianbutheknewPeterverywellandvisitedhiminGlynnHouseinCornwall.Somyprojectwas

totrytoresolvethis.Iwoulduseanapparatus,whichIpartlyassembledmyself,tomeasureH+/Oratiosforthefirstyearorso.ThenwemanagedtoinhibittheH+/OwithEGTAifIrememberrightly;thereaftertheprojectwasn’tgoingterriblyfar.SoImovedontoexaminingeffectsofionophoreantibiotics,followingonsomeapproachesdevisedbyBrianand,Ithink,KeithorTony.IwasusingsomenewantibioticsthathadlargelybeendiscoveredinHenryLardy’slaboratoryintheUSA,whichiswhyIlaterwenttoMadison.

IwasstudyingtheireffectsonmyownredcellsmeasuringK+/H+exchangeswithelectrodeswhenJohnandIrealised(duringourusualpublunchasIrecall)thattheliposomemodelmembranesheusedwereawonderfulsystemtodoasimilarkindofthing.JohnandItendedtoworkinparallelandwedevisedsomegreatexperimentswithradioactivesodium,potassium,rubidiumandcaesiumdowninthehotroom,buriedinthelumpofrockundertheMedicalSchool.Wewereveryinexperiencedsowedraftedonepaper–thesedaysyou’dprobablymaketwoorthreepapersoutofit;weputeverythinginfromtheeffectsofalltheantibioticsonallofmitochondria,redcellsandliposomes,interpretedintermsoftheMitchellTheory,andsentitofftotheBiochemicalJournal,whoacceptedit

University of Bristol14 50 Years of Biochemistry at Bristol 15

Interview with…

Peter Henderson

Peter did both his undergraduate and PhD studies at Bristol. Once he had obtained his PhD he lived and worked in Wisconsin, USA. Since returning from the States, Peter has worked at many institutions including the Universities of Leicester and Cambridge, Jichi Medical School in Japan, Guelph University in Canada and Macquarie University in Australia. Peter has been professor of biochemistry and molecular biology at the University of Leeds since 1992.

My advice, to today’s students, would be that rigorous biochemical training enables you to understand

most other disciplines.

Q What brought you to Bristol?

A I’ddoneabiochemistrydegreeatBirminghamandIdidn’twanttogointoresearch.Idefinitelydidn’twanttodoteachingatthatstageandIthoughtImightgointojournalwork.Iwaspersuadedtotakeaveryshortsecretarialcourse,basictypingandshorthand,andIcametodothatinBristol.ThenthejobwithPhilipcameupandIthought‘I’lljustdoitforalittlewhile’andthendecidewhatIwanttodoafterthat.ThenDickcamealongandhewasafixtureinBristolbecausehewashalfwaythroughhisPhDwithPhilipRandle.ThenIhadchildrenandIneverquitemadethemoveintowhatIthoughtImightdowhenIfirstgraduated.

Q What was Philip Randle like?

A ThefirsttimeImetPhilipwasonwhatmusthavebeenhisfirstorseconddayinBristol.Irememberarrivingandknockingonhisdoor.Iwentinandhewassittingonasofa,quitelowdown.HestartedgettingupandIwatchedhimandhekeptgoingup,andup,andup.Hewasaverybigman!

Itwasreallygoodbeingthereatthestart.ThedepartmentwassmallandIfeltverymuchapartofitandappreciated,andtherewasagreatsociallifearoundthat.Philip,andhiswifeElizabeth,entertainedusquitealotbutitwasalwaysfeltratherhardworkbecausetheydidn’treallydosmalltalk.Hewasamanoffewwords.Itwasn’tworthsayinganythingifitdidn’thavesignificance.IremembersomeofthoseearlydinnerpartieswithDickwhenIfoundmyselfresortingtoinanitieslike‘whereareyougoingonholiday?’totryandovercomethesilences.

IremembertoothatPhilip,veryunusuallyatthetime,insistedthateveryoneintheDepartmentcallhimPhilip,whichwasverymuchfrownedupon,generally.I’dspeaktosecretariesinotherdepartmentsandtheirrelationshipwiththeirHeadofDepartmentwastotallydifferent–theywouldrefertotheirHeadas‘theProfessor’whereasPhiliphadamuchmoreequalandcollaborativeapproachtorunningtheplace.Hewasalsoaverythoughtfulmanandwasverywillingtogivemealotofresponsibility.Hewasareallygoodmantoworkfor.

WithintheUniversityingeneral,thingswereconductedinsuchaformalwaycomparedwithnowadays.TheDeanofMedicineatthattimewasProfessorDarlinganditamusedmetohearPhilip’stelephoneconversationswithhimstarting‘goodmorningDarling’perhaps.AlsotherewasaDrHoneyinChemistry,soyoucanimagine!

Q What changes to the Department are you aware of?

A It’ssuchadifferentplacenow.There’sbeenenormouschange.WhenIfirststarted,theBiochemistryDepartmentwasjusttwoorthreepeopletransferredfromotherdepartments,butnewappointmentswerecominginthickandfast.TheyweremainlypeoplefromCambridgefollowingPhilip;everydaytherewerenewpeoplearriving.IthinktherewereeightPhDstudentsinthefirstyearsoobviouslythere’sbeenamassivechangeinnumberssincethen.AfterI’dhadthreechildren,IdecidedIwantedtodosomethingdifferentsoIstartedapart-timeresearchassistantjobintheInnerCourt.AtthattimeitdidseemlikequiteaseparatedomainfromtheMedicalSchool,butluckilythesectionscametogetheranditwasmorecohesiveafterthat.


Q Who do you particularly remember from that time?

A IrememberAnneColewhobecameagoodfriend,andCharlesPhelpswhowasthereatthestart,andthenallthePhDstudentsarrived–Philip’slotinvariousstagesofcompletionandothersjuststartingoff.Therewerealsolargenumbersofvisitingscientistsfromoverseas.Philipreallyencouragedthisandthatwasanotherlovelydimension.InparticulartherewerepeoplefromAsia–awomanfromSingaporeandonefromSriLanka–whoweredelightful,andothersfromAustralia,Canada,USA,Spain,agreatguyfromVenezuela;allovertheworldinfact.Itfeltreallymulticulturalandbecausetherewererelativelyfewinthedepartment,theimpactofhavingthemixofpeoplewasmuchstronger.Manyofuswereofasimilarage,itwasareallyyoungdepartment;IthinkPhilipwasunder40whenhewasappointedandtheaverageagewasprobablyaround25to30.

Q Were there many women in the Department at that time?

A IrememberAnneColeandMollieLuscombefromtheearlydays,andthevisitingscientiststhatcamefromAsiaweremainlyfemale.Theywerereallycommittedtofurtheringtheircareers;reallyinteresting,strongwomen.IntermsofPhDstudentsIcanonlyrememberonewomanfromthatperiod.Thedepartmentwasheavilyskewedtowardsmales.HilaryMuirheadwasthefirstwomantoberecruitedfromoutside.I’venotreallythoughtaboutthechallengesshemusthavefacedbeforebutIguessHilarywasquiteatrailblazer.

Q Why did you choose biochemistry?

A WhenIwasatschoolmostoftheteachersseemedprettyoldbutwhenyou’reatthatstage,inyourlife,Iguesseveryoneovertheageof30seemsancient.Tomemaths,physics,biologyandchemistrywereallfairlydull.Thenanewchemistryteacherarrivedandhewasinspirational–suddenlychemistrybecameareallyexcitingsubject.Onedayhesaid‘ifIhadmytimeoveragainIwoulddobiochemistry,it’sthesubjectofthefuture.’SoIthoughtI’dbetterdobiochemistry!IlikedthetheorybutInevergotonverywellwiththepracticalssoitwasobviousIwasn’tgoingtobearesearcher.IhadagreattimeatuniversityandIdofindbiochemistryintriguingbutIwasnevercutoutforresearch.

Q What are your best memories of Bristol Biochemistry?

A WhenDickandhisgenerationarriveditwassuchanexcitingperiod,atimeofalotoffriendships.Idorememberthatsideveryfondly.PeoplegotonverywellandwereworkinghardtoestablishthemselvesandtheDepartment.Therewasahighlevelofenergyabouttheplaceandafeelingofcollaboration.I’mnotsureI’vematchedthatinanyjobsince.


Interview with…

Jan DentonJan worked as Philip Randle’s secretary from the first day of the new Department, 1 April 1964, until autumn 1967. She met her husband, Dick Denton, at Bristol while he was studying for his PhD under Philip. Around 1970 she worked part-time as a research assistant with Herman Watson among others, and also worked in Senate House for a short time. After leaving the University, Jan began a career in secondary school teaching and later as an educational consultant.

There were large numbers of visiting scientists from overseas. Philip really encouraged this.

There were people from Asia, Australia, Canada, USA, and Spain; all over the world in fact.

It felt really multicultural and because there were relatively few in the department, the impact of having the mix

of people was much stronger.

Q Can you describe the time of your arrival at Bristol?

A IstartedmyPhDinCambridgewithPhilipRandle.WhenhewasappointedastheHeadofthenewBiochemistryDepartmentatBristolIfollowedhim.IwasthefirstofquiteafewpeoplefromCambridge.It’samazingthatIcanstillremembermyfirstday;itwasnearly50yearsago.FromPhilipRandle’sgroup,IwasthefirstpersontoarriveandIrememberPhilipsayingtome‘right,we’vegottosetthelabup’.Sohepointedmetothelabandsaid‘getitworking’,whichIdid.

Q Along with many others you decided to stay in Bristol, why was that?

A Yes,Icertainlydidn’texpecttostayanduntilrelativelyrecently,IassumedImightmove.Iwasofferedquiteafewotherjobsovertheyears,butIcouldneverquitefindthemattractiveenough.Ithinkit’sacharacteristicofBristolthatsomanypeoplehavestayed.I’vegotveryfondmemoriesofBristolandmywifeandImanagedtogetmarriedwithinsixmonthsoflivinghere.It’saverynicecity,averygooddepartmentandI’mverysettled.

Q What have found to be most enjoyable about working at Bristol?

A It’sdefinitelybeentheresearchstudents;they’vebeenanabsolutejoy.Iliketeaching,andIenjoyedbeingHeadoftheDepartment–itwasaveryexcitingtime.I’dalsosaytheresearchitself.I’vebeenverylucky,I’vehadsomereallyexcitingmomentsinresearch.

Q Could you name some of the highlights?

A Therearethreeimportantones.Firstly,showingthatinsulinactivatedtwoenzymesinvolvedinfattyacidsynthesis.Secondly,showingthatcalciumactivatedabunchofenzymesinsidemitochondria,whichisstilltheareaIworkon.Finally,wehavefoundtheproteinwhichtransferspyruvateintomitochondria.AndrewHalestrapandIfirstidentifiedthattheremustbesuchaprotein,andveryrecentlythetwoofusalongwitharesearchstudent,ChloeBurns,havefoundit.

WhenDickDentontookoverfromBrianChappellasHeadofDepartmenttherewereagreatmanychangestakingplaceinBristolBiochemistry.Therewasasignificantchangeinstaffarisingfromalargenumberofretirements.Duringthistime,theDepartmentwasalsoverysuccessfulinitsbidsforcapitalworks,includingwinningfundingtobuildtheIntegratedSignallingLaboratories.

Q If you could name people from the School of Biochemistry who have had a considerable impact on your life, and career, who would they be?

A Firstly,mywife,ofcourse!ShewasPhilipRandle’ssecretaryandarrivedwithhimonthe1April1964.Mystudentsandpostdocstoo;it’shardtosingleoutindividualsamongstthem.Additionally,thetwopreviousheadshadagreatinfluence–ChappellandRandle–particularlyRandle.


Q What significant changes to biochemistry at Bristol, have taken place during your time here?

A DickDentoncitesthegrowthoftheDepartmentasoneofthemajorchangestohavetakenplacesincetheDepartment’sinception.Uponhisarrival,hesays,therewereonlytwoorthreemembersofteachingstaff,whilethefirstBiochemistryclasswasmadeupofaroundsevenstudents.UnderPhilipRandle’sleadershiptheDepartmentdoubledinsize,andhasmorethandoubledagaininthe40yearssincehisdeparture.Aswellastheunbelievableamountofpaperwork,andgeneralbureaucracywhichwasn’ttherebefore,anotherwouldbeHealthandSafety.Wewerenotwellbehavedintheearlydays;inthefirstfiveyearsorsooneparticularjokewastoputdryiceinrubbertubing,tieaknotineitherend,andwalkaway.ThatjokewasafavouriteofBrianChappell,ifIremembercorrectly.

Earlyontherewerelotsofpranks.InM101,anewlabwemovedtosevenoreightyearsaftertheDepartmentfirstopened,therewasacockroachinfestation.Thesecockroachesfoundthemselvesinvariousplaces.Thefunniestjokeinvolvedoneguywhoneededhisglasses,buttendednottousethemasmuchasheshould,sooneoftheotherchapsinthelabstucktwocockroachestohisglasseswithSellotapesowhenheputthemon,hewaslookingstraightatthesecockroaches.


A Thedepartmenthashadmanygoodtimes.Whatmakesthedepartmentsuccessful,Ithink,isthemanygoodmembersofstaff,lotsofproductivecollaborationsandtheverygoodstudents.

Q What advice would you give new students starting biochemistry in Bristol this year?

A WhatimmediatelycomestomindistheHeadofDepartmentspeechIusedtomaketothefirstyears.Iusedtosay‘workhard,playhard’.Also,Iadvisethattheymakesuretoexploitallthefacilities.Mostundergraduateshaveagreattimehere.


Interview with…

Dick Denton Dick arrived at Bristol, in 1964, three months after Professor Sir Philip Randle. He began as a PhD student, finishing the work he started with Philip at Cambridge. He was then appointed to a temporary lectureship and in time proceeded to become lecturer, reader, professor, head of department and finally, dean. Since his retirement, in 2005, he has continued to work part-time carrying out teaching and research.

There were a great many changes taking place in Bristol Biochemistry… a significant change in staff,

arising from a large number of retirements… the Department was also very successful in its bids for

capital works, including winning funding to build the Integrated Signalling Laboratories.

Top left to bottom right: The Medical Sciences Building as viewed from the centre of Bristol; Chris Proud in earlier days; Becky Jones in the lab; Len Hall running molecular genetics undergraduate practical; Rachel Curnock in the new C50 labs; Undergraduate students during the late 80’s/early 90’s in

A89 of the Biology Building; Molecular Enzymology coffee room; Entrance to the Inner Court Biochemistry laboratories in the 1980s; Freddie Gutfreund getting to grips with turnover; Fiona Diffin at work in D40; Rachel Curnock in the new C50 labs; A Schools Week class in the biochemistry teaching labs.

Gallery: now and then




A IsuspectwhatIrememberwasanamalgamoffirstdays;itwasbackin1986,soquitealongtimeagonow.Atthatpoint,thelabsIworkedinwereinInnerCourtandrightdowninthebasement.WhileIwasn’tdisappointedwhenIcametothisuniversity,itwasn’ttheglamourthatonewouldassociatewiththemoreinterestingresearchlabsinthecountry.Alongwithafairlyhonourabletraditioninresearch,itwasmuchmoremundaneandalittlebitdingierthanIhadexpected.Irememberbeinggivenalargejarofgreen-ishsludgeandtold‘there’ssomeenzymeactivityinthere,doyouwanttoseeifyoucangetthatout?’Isaid‘yes,sure’anditwasthenthatIrealisedthatoneofthemoreexcitingandfun,butdefinitelychallenging,thingsaboutdoingaPhDwasthattheybasicallysay‘Welcome!Here’saverylongpieceofrope;ifyouwanttogoanddothingswiththatrope–that’sgreatandifyouhangyourselfwithit–well,ithappens’.

Q Why did you choose to study biochemistry?

A That’sagoodquestion.IwantedtobeavetandIdidn’tgetthegradesandmyMumsaid‘whataboutbiochemistry?Itlookslikeanupandcomingdiscipline.’IlookedatitanditfittedmyA-levelsandIknewIwantedtostudyscience,particularlybiologicalsciencesandIthoughtbiochemistrysoundedinteresting.Itwasn’tabig,well-thought-outdecision;itwaslikesomanydecisionsinlife,Ijustthought‘yeah,alright,I’lldothat’.

Q Who have you most enjoyed working with?

A SteveGamblin,GideonDavieswhowasaresearchassistantwhostartedwithHilaryatthesametimeasIdid.IrememberHermanWatsonandJennyLittlechild.IrememberJanet,whowaswonderfulandindispensable.Shewoulddoallthewashingupforusandtakeallthephotosandalltherestofit.Shewasverykind,andanalmostreassuringpersontohavethere.TherewasaguycalledAndrew,whowasinawheelchairandusedtorunthecomputers.Someof

thelecturersIrememberareSteveHalford,theHeadoftheDepartmentandBrianChappell.IcertainlyrememberTonyClarke.IwasactuallyquiteunusualinthatIknewpeopleoutsideBristolUniversityandwhenImoveddownthere,therewerequiteafewpeoplewhoIalreadyknew.ItendedtomixwithpeopleoutsidetheUniversity.

Q Do you have a best memory of Bristol?

A ParadoxicallyIrememberwritingupbecauseIwroteupinaremarkablydisciplinedway,forme,butitwasprobablyquiteatypical.Iwrote,prettymuch,nine-to-five,fivedaysaweekandthenI’dcomeinforahalf-dayonaSundayandI’dwritethen.Iwroteitalldowninpen,long-hand,andthenI’dtypeitalluponthecomputer.Ididabitofeditinginbetween,thengaveittoHilarytolookover.Shemadeafewsuggestionsandalterationsbutbasicallyhandeditbacktomeandsaid‘that’sfine’.IessentiallywrotemyPhDupinthreemonthsandtheversionIsubmittedwasnotsubstantiallydifferentfromtheoriginalversionIputdown.Icameoutfrommyadvisorwithafewcorrectionstodoanditwasapass.Idon’tknowhoweasilyIpassed;youonlydoitonce.

MytimeatBristolwasreallyimportanttome.There’sabitofmethatreallyregretsthatIeitherdidn’tpersevereenough,orwasn’tgoodenoughtobearesearchscientistbecauseI’dstilllovetobeone.There’salittlebitofsadnessaboutthatbutthetrainingIgotinBristol;therigour,thesharing,theideas,havedefinitelysetmeupforlife.IthinkbackonitincrediblyfondlyandI’mreallygladIwentthere.

Q Why do you think Bristol has such a good reputation for biochemistry?

A Itmanagestorecruitgoodpeopleandthere’sanucleusofintelligent,thoughtfulresearcherstherewhoarebothsupportiveandintelligentlycriticalaboutwhatyoudo.It’sreallyinteresting.I’vebeenajournalistforthelasttwentyyearsandI’vebeeneffectivelylookingatscienceandI’mveryawarethatthetrainingIgotinresearchatBristolwas

extremelygood.Itequippedmetoaskrigorousquestions,notonlyaboutmyownresearchbutalsoinmycapacityasajournalist,abouttheresearchofothersandtobeabletoidentifywhat’sgood,what’spoorandtospotholesinotherpeoples’arguments.Iwasn’tevertaughtthatbutifsomethingwasn’tright,orotherpeople’sworkwasn’trightthenwe’ddiscussitandtalkitthrough.Justbeinginthatenvironmentofclever,analytical,peopleisself-sustainingbecausetheywouldthengetgood,new,peoplecominginanditwasrigorous–intelligentlyso.

Q What did you do once you had left Bristol?

A ThepottedhistoryItellisthatIreallyenjoyeddoingmyPhD.WhenIstartedmypostdocitbegantodawnonmethatwhileIwasn’tbad,Iwasn’tasgoodassomeoftheotherpeopleIworkedwith.Iwasn’taparticularlygoodbenchscientist.IbegantorealisethatbeingaresearchscientistisanincrediblyvaluableandrewardingcareerbutIdidn’tthinkIwasgoingtobeasgoodatitasI’dliketohavebeen.Sothatleftmeinaquandaryoverwhattodo.Thenakeyeventhappenedandironically,there’sananniversaryeventcomingupforthisnextyearaswellTherewasashort-waveradiostationrunninginBristolcalledFemFMwhichwasBritain’sfirstall-womenradiostation.Iwentalongtohelpoutonit.Youmayaskanobviousquestion,Ihavenothingtohide;IamasIwasborn,Iamdefinitelyamanandtherewasamen’shour.Sotherewere23hoursofwomenbroadcastersandthenanhourofmenandIgotinvolvedinthat.Itwasareallight-onmomentformebecauseIrealisedthatwhileIdidn’thavethetechnicalskills,I’dspentmanyyearslisteningtospeechradio,(Radio4)soIknewhowaninterviewfeltandhowaninterviewshouldgo.IdidthatandIabsolutelyfellinlovewithradio.ThatwasaboutayearandahalfintomypostdocandIthought‘right,thisiswhatIwanttodo’.

It’sahugelynaïvethingtosayIwanttogoandmakeradioprogrammes,becausethere’sanawfullotofpeoplewhowanttodoitandveryfewjobsaround,butIwasyoungandidealistic.Basically,I’dcomeintocollegeanddomyworkduringthedayandthenintheeveningsIwouldsitathomeandmakeradioprogrammeswithafewfriends.WegotsomestuffonBBCRadioBristolandIgotintouchwithpeopleintheBBCRadioScienceUnitandaskedtogoandseethemandtheneventually,whenIcametotheendofmypostdoc,Isetouttomakeacareerinradio.

ThefirstjobIgotwasasajuniorresearcheronaTVprogrammecalledBigScienceonBBC2,andI’llbehonestwithyou,Ihatedit.TVwasn’tforme.AfterthatIwasoffered

athree-monthtraineepositionattheBBCRadioScienceUnit,whichItookandIstayedthereforsevenyears.Ileftaround2001,Iwasheadhuntedtobetheeditorofasmall,Bristol-based,satellitedigitalTVcompanycalledEinsteinTV,whichspecialisedinscience.Thatwentbustafteracoupleofyears,whichisnotuncommoninthisarea,andI’vebeenprettymuchfreelanceeversince.TodayIstillmakeprogrammesforRadio4,Istillwriteforvariouspublications,butIhaven’twrittenforawhile.IhadacolumnintheTimesforawhileandoneofmymoreinterestingjobswasbeingthescienceeditorforMaximmagazine.Ibetyoudidn’tknowtheyhadascienceeditor!ItbasicallyinvolvedfindingasmanystoriesaboutsexasIpossiblycould.Notentirelythough,Ialsowroteaboutgadgetsandquirkylittlestories,Ididthatforawhile.

MakingprogrammesforRadio4,wasand,isoneofthehardestandmostinterestingthingsIdo.ThemostrewardingjobIhadwasscienceeditorfortheBBCWorldService.Ididthatforafewyearsanditwasreallyinteresting.Findingandbroadcastingthescience,thatwasinteresting,toaround150millionpeoplewholistened,fascinatedme.Ialsofounditahugeresponsibilitybecauseitwasmyjudgement,plusthejudgementofafewotherpeople,whichdecidedwhatwasworthtalkingaboutandwhatwasn’t.

ThereisonethingI’dliketoaddaboutmyjob,ifImay,isthatoneoftheenormousprivilegesandpleasuresIhaveatthemomentisthatIgettogoandtalktoallsortsofpeople.IcanringupNobelLaureatesandthey’llpickupthephoneandtalktome.I’dspokentosomeofthemostextraordinaryscientists;I’vespokentoJimWatson(ofWatsonandCrickfame)andAndreGeim,whodevelopedgraphene.

Q What advice would you give to new students in Biochemistry?

A Expectittogowrongregularlyandexpectresultsyoudidn’texpectbuttalktoyourcolleagues,talktoyoursupervisor,sharetheresources,shareyourwork,shareyourideas,shareyourstories.Thisideathat,inscience,youneedtohangonbeforesomethingispublished–no!Goandtalktopeople,becauseideasthriveandmultiplywhenyoutalktopeople,theyshrivelanddieifyoukeepthemtoyourself.Wateryourideaswithplentyofinputfromotherpeople;listentothemandtheirideasaswell.Keepideasmovingandcirculatingbytalkingbecausethatway,newthingscomealong.Ideasalwayscomeatthejunctionsofdisciplinesandatthejunctionsofpeople.Ideasdon’tcomefrompeoplesittinginanisolatedlittleroomthinkingtothemselves,ideascomewhenyoushare.

Interview with…

Toby MurcottToby obtained his BSc at York before applying to do a PhD with Hilary Muirhead at the University of Bristol. Upon completion of his PhD, he began postdoctoral study. At the same time he worked for a Bristol-based short-wave radio station which paved the way for his future career in radio journalism. He has had a variety of jobs since, including working for the BBC World Service.

This idea that, in science, you need to hang on before something is published – no! Go and talk to

people, because ideas thrive and multiply when you talk to people.

Q Can you describe your time at Bristol?

A MyPhDwithDickinvolvedstudyingagroupofmitochondrialdehydrogenasesthathe’dshown,withJimMcCormack,wereregulatedbycalciumions.IwastaskedwithwhatDickthoughtweresomefairlystraightforwardexperimentstoshowthattheirsensitivitytocalciumwasthesamein situ,insidepermeabilizedmitochondria,asafterpurification.Tooursurprisewefoundthatthecalciumsensitivityofthedehydrogenasesdifferedmarkedlyfromoneanother.MyPhDeventuallybecamebasedontryingtoelucidatethereasons,atthemolecularlevel,forthosedifferences,andwhatthepointwasmetabolically.Thisissomethingwhich28yearslaterI’mstillinterestedinandsomethingI’mstilltryingtotackle,alongwithDick!

IthendidashortpostdocwithDicklookingatinsulinsignallingbeforebeingawardedaTravellingFellowshipfromtheMRCtoworkinGeneva,oninsulinsecretion,withClaesWollheim.

IhadaveryproductivetimeinGenevabutwastemptedbacktoBristolin1993todoanotherbriefpostdocwithDickandJeremy.Wesetupsomenicenewapproachesforstudyingsignallinginsinglecellsusingemergingtools,suchasgreenfluorescentprotein,andgotacoupleofverynicepapers.Asaresult,Iwasfortunateenoughtobemadealecturerin1995.FromthenonIworkedoninsulinsecretion,increasinglytotrytounderstandhowvariantsinthehumangenome,whichpredisposeindividualstowards

type-2diabetes,actuallyworkatthemolecularlevel.Iwaseventuallyluredaway,toImperialCollege,in2006withtheprospectofabitmoreresourcetodevelopanimalmodelsbutIcontinuetointeractwithseveralpeopleinBristolandit’sagreatjoytodoso.

Q What brought you to Bristol originally?

A IlookedatvariousplacestodoaPhD,includingCambridge.TheguyIinterviewedwiththere,RickMartin,wasaformerstudentofDick’sandhetoldme(Iparaphraseonlyslightly):‘ifyou’regiventhechancetogotoBristol,whatthey’redoingthereisaheadofwhatwe’redoinghere…’.Iwasalsoveryinterestedintheprogrammeofwork;IwasfascinatedbycellsignallingandIhadjustreadworkfromthegroupinBristolsoIthoughtBristol’swhereit’sat.WhenIvisitedBristolandspoketopeople,suchasPatienceBarrowtheadmissionstutor,Igottheimpressionthatbesidesbeinganacademicallystrongdepartmenttherewasastrongcommitmenttolookingafterstudentsasindividualsandhelpingthemdevelopbothprofessionallyandpersonally.Doubtlessthisisanadvantageofbeingarelativelysmallandstabledepartment.InanycaseitprovidedasuperbenvironmentforstudentsatthetimeandI’msureitstilldoes.Addedtothat,Bristolisagreatplacetolive.Ithasalltheadvantagesofacitybutissmallandcompactenoughtofeellikeasmalltown.Thejoysofliving15minutesfromthelabcan’tbeoverstated!


Q Which members of the Department do you remember inparticular?

A Ireceivedstrongsupportfrom,andeventuallysetupproductivecollaborationswith,anumberofmembersofstaffnotablyAndrewHalestrapandJohnMcGivan,aswellasChrisProud.BrianChappellwasHeadofDepartmentatthetimewhenIwasastudentandhewasalsoaco-assessorofmyPhD.ThemostfrighteningtalkI’veeverhadtogivewasmyyear-onePhDpresentation,tothewholedepartment,in1986.BrianaskedmealotofpenetratingquestionswhichIansweredquitebadlyasIrecall.Fortunatelyhedidn’tholdthatagainstmeinmyvivatwoyearslater.

IntermsofstructuralbiologytherewasHermanWatsonandJohnHolbrook,whowereverybigplayersinthatareaatthetime.TonyClarkewasappointedtoalecturershipnotlongafterIstartedasaPhDstudentandhewasalsoastronginfluence.ThemembranebiologysidewasverystrongwithMikeTannerstudyingvariousredbloodcelltransportersandHilaryMuirheadonthestructuralsidewasagreatsupport.ThefactthatasPhDstudentswepresentedtothewholeDepartment,andlearntfromthewholeFacultyhowtointerrogatevisitingspeakerswasalsoaboon.

Q What are your best memories from that time?

A Scientifically,turningupthingsthatyoudon’texpecttosee–semi-Eurekamomentsweregreat.Serendipitousfindings,forexamplefindinganewwayofpurifyingoneoftheenzymesIwasworkingon,alsoprovidednicemoments.Socially,therearetoomanytorecount!Although,amongstthemostmemorableIguessweretheM101outings–goingtoLymeRegisortotheForestofDeantoknockacricketballaboutanddrinktoomuch!Wewouldalso,inasimilarvein,gooccasionallytotheRobinHoodorHighburyVaults,seatsofhighlearningwhichIunderstandaresadlyless-frequentedthesedays.Inthepre-Facebook,1980s/90s,daysthesewereverymuch

thevehiclesforsocialinteraction,againmadeeasierbythefactthatitwasjustashortstrollhomeafterwards.

Q What changes took place while you were there?

A It’sreallythelackofchangethat’squitestrikinginBristol.Myimpressionisthatmanywhoarerecruitedtheretendtostaythankstoboththequalityofthescience/teaching,andofcoursethequalityoflife.OfthefewchangesthatIdidexperience,theJointInfrastructureFundAwardhelpedenormouslyinallowingustocreateandoccupysomereallystate-of-the-artlabs,eventhoughitwassadtobidfarewelltotheelegantparquetflooringandwoodenbenchesofM101/C101!

Q What have been the most important scientific advancements to come out of Bristol Biochemistry?

A Therehavebeenmany.Onthemetabolicside,thecontributionsofPhilipRandlestandout,thoughtobefairmuchoftheinitialworkwasdoneatCambridge.Hiselucidationofthe‘RandleCycle’andthewholeinteractionbetweencarbohydratesandfatinmetabolismwerehugecontributionstophysiologyandmedicine.DickDenton’scontributions(initiallywithSirPhilip)

toourunderstandingofmitochondrialmetabolismwerealsofundamental,aswereBrianChappell’sandJohnMcGivan’s.SubsequentlyAndrewHalestrapcontributedhugelytotheidentificationofmitochondrialtransportersandtoplasmamembraneaniontransporters.Andrewdidalotofthereallytough,fundamentalworkthat,alittlebitunluckilyforhim,wassubsequentlyusedbyotherslikeGoldsteinandBrowntoclonethecorrespondinggenes.JeremyTavaréalsodidveryimportantworkonsignallingbytheinsulinreceptor.Thiswaschallengingexperimentally,usinglargeamountsofradioactivity,soyouneededtobefairlybravetodoit!ThetranslocationoftheglucosetransporterGLUT-4ininsulinsensitivetissues,whichJeremyestablishedasanassay,isverywell-cited.AlsoJeremy’sstudieswithPeterCullenelucidatingtheroleofPIP-3bindingproteinsinsignallingtransductiondownstreamofreceptortyrosinekinases,islandmarkwork.TheworkdonebyJohnMcGivanonaminoacidtransportsislikewisehugelyrespected.

Q What advice would you give to first-years?

A Interactwithpeople,bothyourpeersandthosewhoarefurtherdownthetrack,it’sincrediblehowmuchyoucanlearnjustbychattinginformally.Beproactiveintermsofmovingoutofyourcomfortzone,bothintermsofsubjectandplace.You’vegottobereadyandenthusiasticaboutseizingopportunitiesandpropellingyourcareerforward.


Interview with…

Guy RutterGuy was at the University of Bristol for 19 years. He studied for his PhD in Bristol and then worked as a postdoc with Dick Denton. Following this he received a travelling fellowship from the Medical Research Council to work in Geneva on insulin secretion. He returned to Bristol and worked briefly, as a postdoc, again with Dick and with Jeremy Tavaré, before being made a lecturer in 1995. He stayed for a further 11 years before moving on to Imperial College where he is now a professor and head of the section of cell biology.

Scientifically, turning up things that you don’t expect to see,

semi-”Eureka” moments, were great. Serendipitous findings, for

example finding a new way of purifying one of the enzymes I was working on provided nice

moments. Socially, there are too many “moments” to recount!

Q Could you describe your time at Bristol and explain your role?

A IcametoBristolin1969whenFreddieGutfreundwasHeadofthemolecularenzymologylab.HermanWatsonhadcomein1968andhehadsetuptheproteincrystallographylaboratoryandIjoinedhimthefollowingyear.WewereintheInnerCourtlaboratoriesinWoodlandRoadforanumberofyearsandthenweeventuallymovedovertotheMedicalSchool.NeitherHermannorIwerebiochemistssoitwasacaseoflearningaswewentalong–asfarasteachingwent.HermanhadalreadymetBobScopeswhowasaleadresearcherattheMeatResearchInstituteatLangford,whichlaterbecamepartofLangfordVetSchool.Hewaspurifyinglotsofproteinsfrommusclesohewassupplyinguswithquiteabitofmaterial.HermanalsosetupacollaborationwiththeOxfordproteincrystallographygroupsoweusedtohaveregularmeetingswiththem.Weworkedonproteincrystallographyforthenext28years.

Q Do you remember your first day at the University of Bristol?

A I’mnotsureIreallyrememberit.IdorememberthatIcameoverforaninterviewthedaytheylandedonthemoon,andtheywerewatchingitintheseniorcommonroomonthetelevision.ThatwasmyfirstvisittotheUniversity.

Q What brought you to the University?

A IcameonFreddieGutfreund’sinvitation.HeinvitedHermanandmetocometoBristol,soHermancamefirstbutthentheyneededsomebodyelse.HermanandIhadbeenworkingtogetherattheMRClabinCambridge.

Q What is your best memory from your time at Bristol?

A Mybestmemoryistheexcitementofthenewproteinstructuresthatcameoutofourwork.

Q What do you think defines Biochemistry at Bristol?

A Ithinkthethingaboutbiochemistryisthatithasinterfaceswithallsortsofsubjects.HermanandIwerebothverymuchphysicistssowewereatoneextremeendofBiochemistryatBristol.ThepeopleinWoodlandRoadweremainlyatthephysicalendbecausetherewasFreddieandDavidTrentham.ThemedicalendwasoverintheMedicalSchool.Wewereratherfarremovedfromalotoftheworkthatwasgoingonthere.Backthenitwasmoreacaseofthetechniquesbeingphysicaltechniquesbuttheproblemswerebiochemicalsoitwasaquestionofhowdoyoudoit?Atotheruniversities,thosedoingsimilarworktouswereplacedindifferentdepartments.Forexample,IthinkatOxfordtheywereactuallyinthezoologydepartmentandinotherplacestheywouldbeinphysics.

Q Why is Biochemistry at Bristol so highly regarded?

A WellIthinkwegetverygoodstudentsandIthinktheteachingisprettygood;it’soneofthefewremainingbiochemistrydepartmentsinthecountry.Theresearchprojectsavailableareprettygoodandpeopleworkprettyhardtogetthem.Idon’tknowwhetherthisisstillthecasebutinmytime,wealwaysmaintainedaprettyrigorousmathematicalaspecttoit;studentshadtodocalculations.Thisdefinitelyhelpswithpeople’sjobprospectsandIthinkit’sworthwhile.


Q What have been the significant changes to the Department?

A Well,I’dsaytheexpansioninsizeoftheDepartment.InBiochemistryyouwerealwaysaheadofthetextbooks;theywereneverreallyup-to-datebecausethesubjectwasmovingandchangingallthetime.Intermsofthird-yearteachingitwasverymuchresearch-oriented.Ithasgrownfromabout40studentsinmydaytoover100today.Ithinkthatmakesitmuchmoredifficulttogettoknoweachstudent.

Q Can you name some key scientific advancements?

A IcanonlyreallytalkaboutwhatIamfamiliarwithandwhatwewereworkingonwasthestructuresoftheglycolyticenzymes.InconjunctionwiththeOxfordgroup,andalsosomeoftheAmericanuniversities,amajorachievementwasprettymuchcompletingthatpathwaywithmuchoftheworkoriginatingfromBristol.


A IthinkthemostinfluentialpeoplewouldhavebeenHermanandFreddie.Wealsohadsomeverygoodstudentstoo.IthinkDavidStammerswasmyfirststudentandhewentontodoprettywell.DavidShottonwashereasapostdoctoo,atthebeginning,andthenhemovedtoOxford.

Q Did being one of the only women in the Department pose challenges?

A Itcertainlydid,yes.Ithinkoneofthedangersisthatcertainpeoplewillsaythatyou’veonlybeenputonacommitteebecausetheyneedawomantobethere.Idon’tknowifthatstillhappensbutthatwasoneofthemainchallenges.OfthetwootherwomeninBiochemistryatthetime,therewasAnneColewholookedafterthedentistsandwasaseniorlecturerbutshemainlyconcentratedonteachingandshealsowroteaverygoodtextbookfordentalstudents.TherewasalsoMollieLuscombewhoworkedwithPhilipRandle.Itisstillthecasethatthereisn’tagreatdealofwomeninseniorrolesinbiochemistry.

Q Why do you think there are not many senior women in biochemistry?

A Ithinkyouneedtobeabletogetmoneyin.Inordertoretainyourpositionyouhavegottogetgrants.Inthepastwomenwouldfindithardertogetgrants;itdoesn’tseemtobeashardasitusedtobe.Therearenowvariousgrantswhichencouragewomentocomebackafterhavingfamilies,andthingslikethat.ForexampletheRoyalSocietyhadvarioussocietiestohelpwomencomeback,therewastheDorothyHodgkinFellowshipforone.Also,IthinkitwasBirkbeck,inLondon,whichpioneeredjob-sharing;theyhadtwowomensharingalectureshipandtheysurmisedtheygotconsiderablymoreoutofthetwoofthemthantheydidfromhavingjusttheonelecturer.


Interview with…

Hilary MuirheadHilary arrived at Bristol in 1969 and worked with Herman Watson. The duo established protein crystallography in Bristol. They were based in the Inner Court, and both Herman and Hilary worked together at the University of Bristol for a total of 28 years.

In Biochemistry you were always ahead of the textbooks;

they were never really up-to-date, because the subject is moving and

changing all the time.Hilary with the early PDP8 computer.

Q When did you come to Bristol?

A IarrivedinBristoleightyearsago,in2005.ImanagedtogetaspotinMarkDillingham’slabsomewhatfortuitouslybecauseIleftsortingoutmyPhDuntilverylateandMarkneededtofillaposition.Iendedupcominghereanditwasthebestthingthatcouldeverhavehappened.IwasMark’sfirstPhDstudent,andforthattobethefirstexperienceofmyacademiccareer,itcouldn’thavebeenanybetter;Ireallywasverylucky.

Q What did you like about Bristol?

A Thecity,Ialreadyknewwell;Ihavealotoffamilyhereandithasaverylaidbackfeelandjustenoughgoingontokeepyouinterested.ComingfromLondon,it’simportantformethatBristolhasabusyenoughfeel.Ihavetobehonestthough,ImainlycametoBristolbecauseofMark’sworkratherthanthecityitself.Butit’sagreatplacetobe.Iwouldhappilycomebackhere.It’saplaceI’dbehappytosettledowninandadepartmentI’dbehappytobeapartof–ifIwasofferedapermanentposition.

Q What was it about Mark’s work that made you want to come here?

A Iwasprettydisillusionedwithmyundergraduateproject;Ididn’treallyenjoymostofitbuttheninthelastsixmonthswehadalecturecoursebyaprettybignameinthefieldof

E.ColiandDNAdamageresponse(BobLloyd)andsomeofMark’sworkcameupinthatlecturecourse,andthenIfoundoutthatMarkwasadvertisingapositionandthatwasthat.Imethimandwegotalongverywellonapersonallevelsoitwasprettyobviousthatthiswastheplacetocome.

Q What do you remember about your first day at the University?

A Iremembermyinterviewalotbetter.IarrivedformyinterviewandthefirstthingIdidwastogoandhavecoffeeandlunchandbeforeIrealiseditthatwastheinterview.Markisaverylaidbackcharacter.IntheendIwaswalkeddowntothetrainstationandsentonmywaysoIthoughtthisisagoodfeeling.Fortunatelynooneelseseemedtobeapplyingfortheposition,soIgotit.

Q How did you find your time here?

A Itwasreallyamazing.AfterfinishingatBristolIwenttoNewYorkandthatwasgreat,Iwenttoaverybiginstitute.I’mnowinahugelabwithCancerResearchinLondonbutMark’slabwasstillthemostfunI’vehad.Beinginalabwherethereareonlyoneortwopeoplewasgreatbecauseyougetareallyhands-onexperienceandyoulearnfromthemdirectlywhichIthinkiswhyIwasabletobesuccessfulasaPostdoc.Itwasthatone-on-onepracticalhelpbutalsolearninghowotherpeoplethink,whichiscriticalasascientist.


Q Did you have much interaction with other members of the Department?

A IcertainlydidinD40,whichwasthegroupofpeopleworkingonnucleicacidenzymes.Therewerefourorfivelabgroupsallsharingalabspacewhichisrelativelyunique;I’veneverbeenanywhereelselikethat.Inotherplaceseveryoneisinself-containedunits,whereashereeverybodysharesideasandsharesthespace.AtBristolBiochemistryyoudefinitelygettoknowasmallgroupofpeopleverywellbutperhapsnotthebroaderdepartment.

I’mstillintouchwithpeople,likeMarkDillingham,MarkSzczelkun,andNigelSavery.Allofthosepeoplehavebeenreallysupportiveofme,forexamplebyaskingmebacktotalk,butalsomoregenerally.It’sreallynicetobeintouchwithpeoplewhohavealreadymadethetransitionfrompostdoctoprincipalinvestigator(PI)andwhohavethatknowledgetoshare.

Q Do you have a best memory from your time at Bristol?

A Ihaven’tgotonesinglescientificmemoryas,fortunately,therewerelotsofthem.ProbablythebesttimeIhadinthelabwasn’tactuallyinBristol;itwasonatriptoSpain.WehadacollaboratorinMadridandMarkwasreallygreatatlettingyougetimmersedinthecollaborationandinvolvingyouasastudentintheotheraspectsofthelab.Sowewentforaweekandwespenttheentiretimedoingscienceandtalkingaboutscience.Forme,thatwasanincredibleexperience.Thatcollaborationisstillgoingonnowandithasbeenveryfruitful.Tohavetheopportunitytodothingslikethat,asaPhDstudent,isprettyrare;Icertainlydon’tknowotherstudentsoutsideofMark’slabwhohavehadthosekindsofopportunitiessothatwasahighlightofmytimehere.

Intermsofthesocialaspects,Iwentononeoftheretreats,inmyfirstyear,itwasaday-longretreat.ItwasnicetogetafeelforwhowasintheDepartment.Plus,theChristmaspartywasalwaysfun.

Q Can you remember any funny moments from the Christmas parties?

A No–that’stheproblem!Buteveryonewasagoodlaugh.I’mnotsureifthefunnymomentsthatIcanremembercouldactuallygoonrecord.

Q Do you have any advice for new Biochemistry PhD students?

A Asklotsofquestions.MakeyourPIworkforit.Ithinkthat’sprobablythemostimportantthing.IwasconsciousthatIwasconstantlybuggingmybosstoomuchatthestartbuthesaidtomethathe’dmuchratherIaskedquestionsthanwentingung-hoandgotitwrong.You’reheretolearnfromthemandtheywantyoutolearnfromthembecausetheywanttomouldyouintothekindofscientistwhocanbeproductiveintheirlab.Soasklotsofquestionsandlistentotheiradvice.Atthesametime,trytothinkaboutbecomingmoreindependentastimegoeson.It’simportanttomakethattransitionfromalwaysaskingthingstobecominganindependentscientistwhichiscrucialinthelatterstagesofaPhD.

Q Would you advise someone to do as you did and identify a contact in the field that interests you?

A Definitely,ifyoudon’thaveaspecificinterestitbecomesachallenge.Thatsaid,therearelotsofPhDsnowwherepeopledon’tapplytospecificlabstheyapplytoprogrammes,whichthenhaverotations.Butdothinklongandhardaboutit,becauseacareerinsciencedoesn’tgeteasier.It’snotacaseofgettingaPhDandthenyou’vemadeit,itgetsmoredifficultbutperhapsmorerewardingtoo.


Interview with…

Joe YeelesJoe was a PhD student in Mark Dillingham’s lab after completing his undergraduate BSc in Biochemistry and Genetics at the University of Nottingham. Upon completion of his PhD he worked as a postdoc with Ken Marians at the Memorial Sloan-Kettering Cancer Centre in New York. He now works as a research fellow at the Cancer Research UK London Institute.

I was Mark Dillingham’s first PhD student, and for that to be the first experience of my academic career, it couldn’t have

been any better.

Q How did you end up in Bristol?

A AfterhavingworkedinNewYorkandLondon,myhusbandandIdecidedwewantedtoliveinthecountryandmyexperienceinLondonwasthatyoucouldn’tliveinthecountryanddoresearch.Weallsharedequipmentinthosedaysandyouhadtocomeinatnight-timetodoyourexperiments.SowhenIsawthispostadvertisedIthoughtI’dtryit.Allofmycolleaguessaid‘don’tbesostupid,you’llspendtherestofyourlifearrangingtimetables’.Buttheywerewrong–fortunately.Igaveupresearchentirely,butIhadjuststarteddevelopinganallergytowardsratsandmicesoIwasn’tsorrytogiveupworkingwiththem.Iswitchedtopeople,whichwasmuchnicer.

Q How would you describe your time at the University of Bristol?

A MyrolewasanewpostbecausewhentheDepartmentwassetupbyProfessorRandle,heinheritedone

ortwopeoplefromPhysiologyandonewasCharlesAshfordwhohaddonequiteabitofteachinginthepastbutwasduetoretire.Therewasadministrativeworktodobuttheywantedsomeonewhowasn’tinvolvedinresearchandIwasluckyenoughtobechosen.IworkedwithCharlesforthefirsttwoyearsandthenheretired.Itwasrathernicebecausetherewereonlytwootheradministratorsinthesciencefacultybackthen.OnewasinChemistryandonewasinPhysicsandwewereknownasthe‘Unholy3’!

Q What did your job involve?

A InawayIwasabletochoosethethingsIwantedtodo,andthethingsIdidn’t,whichwasverynice.Alotofmytimewasspentarranginginterviewswithundergraduatestudents.Atthattimeweinterviewedalltheapplicantswewereinterestedin.TowardstheendoftheChristmastermandthefollowingtermwe’dconductinterviews,therewereaboutfivepeoplewhowouldinterviewgroupsof20or30.

Anotheraspectofthejobwasgrants–asideIwasnotsohappywith.People

hadresearchgrants,astheystilldonow,andtheFinanceOfficehadtohandlethemoneyandsomebodyhadtogothroughthebooksandmakesurethatnomistakeswerebeingmadeandpeoplewerespendingthemoneyontherightthings.WealsosetupourownstoreandthatwasdonefairlyearlyonbutProfessorRandlewasresponsibleformakingsurewehadastorejustforBiochemistryandIwasoneofthepeoplewhohadtodothat.

Fortheteachinglabs,oneofmyfirstjobswastositnexttoCharlesAshfordwhenheinterviewedHilaryCrossandNigelEdgell.Ifthewashing-upladies,oranybody,wasunhappythenIwasthecentralpersonwhotheycouldcomeandmoanto,orevenjusttosayhowhappytheywere.BecauseIhadabiochemistrybackgroundIdidtakesometutorials;itwaseitherthemedicalorthevetstudents,butIdidn’tdoanylecturing.

ThereasonIwascalledalecturer/administratorwasbecausetheUniversityGrantsCommitteewouldnotprovidemoneyforanadministratorsotheyhadtocallmealecturereventhoughIdidnotgiveasinglelecture.


Q What was it like working with Philip Randle?

A Hehadanextraordinarilyfriendlydepartment,andhewasdeterminedtokeepitthatway.Peopledidn’tonlyworkforthemselves,theyworkedforeachother–hewasdefinitelytheleaderandwasaverystrongman.Ifoundhimreallyeasytoworkwith,becauseIcameinwithabsolutelynoadminexperiencewhatsoeverandheputupwithme.Charleswasalsoveryhelpful–infactIdidn’thaveenoughtodo,Iwasalittlebitboredinthebeginning,butatleastIwaslearning.


A AnneColewasaskedtolookaftermeonmyfirstday,sosheshowedmearoundandintroducedmetoeverybody–theywereveryfriendly.IparticularlyremembermeetingTrevorGriffithsbecausehewasabrand-newfather.Henowhasthreesons;andoneofhissonshadbeenbornthenightbeforeIstartedandhewasveryexcitedaboutitall.IalsorememberthefollowingweekbecauseitwastheAugustbankholidayandontheTuesdayfollowingthebankholiday,IcameintoworkasusualbutthewholeplacewaslockedupandnobodyhadrememberedtotellmethatwehadtheTuesdayoffaswell!

Q Did you face any challenges being one of the only women working in the Department?

A Formeitwasdifficult,onthesocialside,inaway.IknewallthemenbutIdidn’tknowtheirwives.WhenwehadpartiesRichard,myhusband,camealongandalwaysfeltalittlebitoutofplaceandthatwasabitdifficult.Idon’tknowhowthemenfeltabouthavingafemaleadministrator–theymighthavebeenhorrified,buttheynevermademefeelso.I’dalwaysworkedinlabswhichwerepredominantlymoremale-dominatedsoIdidn’tnoticeadifferencereally.

Q Why do you think science tends to be male-dominated?

A Ithinkprobablythepublicschoolsystemwasatfault,inmycase,becauseitwasquitedifficultforagirltogetdecent,advanced,scientificschooling.Itwasalsoduetothesegregationofgirls’schoolsandboys’schoolsandthatsciencesimplywasn’ttaughtinthegirls’schools.

Q Do you have a best memory from Bristol?

A Ithinktheoverridingmemorywasthatitwasaveryfriendly,cooperativedepartmentforthewholetimeIwasthere.Thingswentwrongbutno-onehelditagainstanybodyandwetriedashardaspossibletobeloyal.Wehadaveryenjoyabletime.WealsohadanenjoyableeveningattheOrangeryatGoldneyHallforwhatwasperhapsthe20thorthe21stbirthdayparty.Quiteafewoftheoldergraduatestudentswholefthadcomeback.

Wealwayshadaverynicesecretarialdepartment.Ithinksomeoneoughttopaytributetothembecausewehadaseriesofsecretaries,Ithinktherewerefourofthemaltogetherandtheygotonwell.Isawalotofthesecretaries,forobviousreasons.Ienjoyedtheinteractionwithpeople;itwassuchachangefromdoingresearch.

Q Can you name some of the most significant people?

A Igotonwiththemall,Ihope!I’msureIwashorribletosomeofthembutIhadanicesideaswell.It’shardtopicksignificantpeoplefromeveryoneintheDepartment.


Interview with…

Patience Barrow Patience read chemistry at Oxford before working as a research assistant at the New York University Medical School. She next worked in Canada, again as a research assistant, at the University of Toronto. Patience then returned to New York and joined a research group working on cancer cells. Following this she moved back to the UK and worked at Middlesex Hospital in London before being appointed as a lecturer/administrator in Biochemistry at Bristol in 1970.

He [Philip Randle] had an extraordinarily friendly department,

and he was determined to keep it that way. People didn’t only

work for themselves, they worked for each other.

Q What made you apply for the job?

A IknewIwantedtogetajobthathadsomethingtodowithbiologybecauseIlovedthesubject.Afterstartingwork,ateighteen,Ididsevenyearsofpart-timelearningeventuallystudyingformyMIBiol.Thiswasreallyhardworkandtookupalotofmysparetime.Iusedmostofmyholidaytoreviseforexams,andalotofcourseworkwasseteachweekmakingitahardslog.

Q Can you describe your early days in the Department?

A Iwasincrediblyluckytogetthejob.MybuswaslateonthemorningofmyinterviewandIwasabouthalf-an-hourlate.AsIwaswalkingtotheMedicalSchoolthechapwhowasinterviewingme,CharlesAshford,waswalkingoutforhislunch!Iftheporterhadn’thailedhim,ashewasjustabouttowalkdownthesteps,IneverwouldhavegotthejobandIneverwouldhaveendedupworkingthere.

IstartedoffinthedentalteachinglabandtherewasanexperiencedtechniciancalledJohnVanStrien,aDutchchap,whohadalreadyspent20yearsworkingintheMedical

School,startingwhenourdepartmentwascalledChemicalPhysiology.ThedentalteachinglabwasrunbyAnneCole.IwasthereforaboutthreemonthsandthenImovedacrosstothemainBiochemistryhonoursteachinglab.LesCorbinwastheseniortechnicianandhepatientlytaughtmethejob.

Iwasverygreen,andabitslow,becauseIwasanxiousnottomakemistakesandtodowell.Lestaughtmethebasicsofthejobwhichhelpedmeeversince.Leswas,andremains,agreatfriendandwearestillinregularcontact.DavidYates,whowasresponsibleforthehonourslab,alsohelpedmeagreatdeal.IlookbackonmytimetherewithgreataffectionasIwasluckyenoughtoworkwithafriendlyteamincludingYvonneWilliams,BettyCroker,WinCuff,WinSwiftandMaryHale.

Q Did you ever consider relocating to a different university?

A NoIdidn’tseriouslyconsiderthis.Howeverwhenmygreatfriend,RogerBrownsey,movedtotakeupapostinVancouver,hisdescriptionsofthelifestyleandbeautyoftheplacemadeabigimpressiononmeanditsoundedfantastic.Hecamebackafewtimesandwestayedintouch.Overthe


yearsI’veheardafewdepressingstoriesfromotherpartsoftheUniversitywheretherewasanapparentlyabrasiverelationshipsbetweenthesupportandacademicstaffandalackofmutualtrust.IthinkI’vebeenreallylucky,I’veneverworkedforanyoneIdidn’tgetonwellwith.

Q Who did you most enjoy working with?

A I’veenjoyedworkingwithallcategoriesofstaffinBiochemistry.DickDentonwasagreatinfluenceonme,particularlyduringmyearlyyearsinM101.Hewasquitedemandingbutheinstilledgoodhabits,taughtmetheessentialsandmademerealisetheimportanceofthoroughpreparationandgoodorganisation.Dicktookagreatinterestinallthepeoplewhoworkedforhimandwasverykeentoseethemadvance.HehelpedmeimmeasurablywithmyMIBiol,allowingmetodomyprojectinhislabwhichwasabigadvantage.Someofmycontemporarieshadtodoalltheirexperimentsatthecollegeitself,usingequipmentwhichwasn’tfamiliartothem.DicksupportedmethroughoutallmytimeassociatedwithbiochemistryresearchandIowehimagreatdeal.

IworkedverycloselywithJeremyTavaré,AndrewHalestrapandPeteCullenafterImovedontoasupervisoryrole;lookingafterB-FloorandD-andE-FloorsISL,withmyofficelocatedonE-Floor.Ireallyfeltthattheytrustedmeandvice versa.TheserelationshipswereespeciallyvaluabletomeduringthemomentousperiodduringtheestablishmentoftheISLandthelaboratorymovesarisingfromthis.IreallyenjoyedworkingdirectlywiththeseniorpostdocswhenIwasaresearchtechnician.TheseincludedJimMcCormack,RogerBrownseyandKellyMoule,whohaveallgoneontobeverysuccessfulandremainfirmfriends.LateronIwasfortunateenoughtobeabletoworkwithGavinWelshandMazWilson.BothgavemefantasticsupportandIvaluetheirfriendshipveryhighly.

Asforsupportstaff,GaryWiltshirewhowastheTechnicalManagerofBiochemistrybetween1997and2012isagreatfriendandcolleague.Weworkedverywelltogetherandsupportedeachotherduringsometoughtimes.GarywasarockformetoleanonandhiscontributiontothesuccessoftheDepartmentwasenormous.

GloriaLambert,whoworkedwithmeonD-andE-Floor,andJoParkeronB-Floor,wereatremendoushelptomeandweretotallydedicatedandreliable,aswellasgoodfriends.DiGarland,formerlyFinancialServicesManager,wasagreatcolleagueandalsoasensitiveandsupportivefriendwhentimesweredifficult.TeresaGornall,withwhomIhappilysharedanofficeonE-Floorforeightyears,wasapleasuretoworkwithandatruefriend.TosumupIthinktheBiochemistryDepartmenthadafamilyfeeltoit,withpeoplerallyingaroundtosupportcolleagueswhentheyneededit.

Q What would you say have been some of the biggest changes to Biochemistry at Bristol?

A Ithinktheapproachofthestudentshaschanged.Thelate1960stoearly70swasatimeofmanystudentprotestmovements,soIthinkthatstudentsusedtobemuchmorepoliticallyawarethantheyarenow.Ithinknowwe’vecomethroughtheThatcherera,studentsaremuchmorefocusedoncomingoutwithadecentqualification.Studentswillalwaysbestudents,they’llalwayshaveagoodtimebutIthinktheyapplythemselvesmorenow.Ithinkthat’sbecausetherearen’tasmanyjobsthesedays.Todayifyouhaveadegreebutitisn’tparticularlygood,there’sachanceyouwon’tgetajob.

IalsothinkthatBristolhastobegivingthestudentsareallygoodexperiencenowbecausealluniversitiesarecompetingforstudentsinwaystheyneverhadtobefore.Alotofitcomesdowntomoney;therewasalotofmoneyaboutbackthen.

Duringmytimeinthehonoursteachinglab,DavidYatesundertookthemodernisationofpracticalclassesprovidedforthestudents.BythetimeIcametoleavethelabDavidhadsuccessfullyfulfilledhisremit.Togetherwithacademiccolleagues,whoranthepracticals,heorganizedtheintroductionofmoresophisticatedexperimentslargelyrelyingonanew,multi-useclassinstrument,theSpectroplus,whichhehaddevelopedincooperationwiththemanfucturers,MSE.


Interview with…

Nigel Edgell

Nigel worked in Bristol Biochemistry for more than 40 years. He joined the University in July 1971 initially as a technician in the teaching laboratory. In the late 1970s he became a research technician, primarily within Dick Denton’s and Andrew Halestrap’s laboratory, and rapidly became one of the most senior technicians within Biochemistry.

Bristol itself is a big attraction. It is

widely held to be one of the nicest cities in

the country. It has a vibrant atmosphere and

many pleasant and interesting places.

Q Tell us about your early years at Bristol?

A Istartedhereasastudentin1964,admittedlyreadingchemistryratherthanbiochemistry.Inthosedays,thebiochemistrycoursewasatwo-yearprogramme,soIdidchemistryinmyfirstyearalongwithmaths.InmysecondyearIdidchemistryandusedbiochemistryasmysubsidiarysubject.IwentalongtoalecturebyJohnWilliamsonsicklecellhaemoglobinsandthisinspiredmetobeabiochemistratherthanachemist.InmyfinalyearIswitchedmyhonourssubjecttobiochemistry.IthendidaPhDwithFreddieGutfreund,from1967to1970.

Q What would you say have been Bristol’s most important scientific advancements over the years?

A Therehavebeenquiteafewactually.IthinkFreddieGutfreundranaverysuccessfullaboratory,someoftheworkhedidonenzymekinetics,andtheseniorpostdocwhothenbecamealecturer,DavidTrentham,didsomereallypioneeringworkonthefastreactionkineticsofmyosin.TherewasalsoaverystrongstructuralgroupledprimarilybythelateHermanWatson.Hehadsomebrilliantstudents,includingDaveStuart,SteveGamblin,GideonDaviesandDaleWigley.Weactuallydidn’treallyrealisehowgoodtheyallwere,untillthey’dbeenandgone,butthatwasapowerfulgroup.It’salsoworthmentioningRichardCogdell,NeilHunterandBazJacksonastheydidsomeveryimportantworkonbioenergetics,essentiallyvalidatingthechemi-osmotichypothesisthatPeterMitchellhadproposedafewyearsearlier,andforwhichhewasawardedtheNobelPrize.

Q What have been some of the most significant changes over the years?

A Therearemanyofthem.Oneofthemainthingswouldbethatlecturersthesedaysappeartohaveamuchtougherjobintermsofallthisstuffcomingdownfromonhigh.Wedidn’thavetobotherwithallthatbureaucracybefore.Anotherofthemostsignificantchangeswasallofusmovingtoonesite.WhenIwasastudentandapostdoc,andlaterajuniorlecturer,theDepartmentwassplitontwosites–halfofusweredowninwhattheycallthemolecularenzymologylaboratoriesonWoodlandRoad,partofEarthSciences,andtheotherhalfoftheDepartmentwasintheMedicalSchool.Itwasonlylater,about1990,thatweallactuallymovedtogetherontoonesite,whichIthinkmadeabigdifferenceandabigimprovement,tothedepartment.Ialsothinkteachinghasnoticeablychangedovertheyears.Theteachingprogrammeisgettingextraprogressiveandmoreregimented.Ibelievethatthejoboftutorialsistoenthusethestudents,nottoteachthemwhattheyhaven’tbeentaughtinthelectures.

Q Who have you most enjoyed working with?

A FreddieGutfreundwasmyscientificgodfather.I’vealsohadaverysuccessfulrelationshipwithNigelBrown,becauseNigelandIwereappointedatthesameappointmentpanel.Togetherwesetupajointlaboratorysohewasveryhelpful,aswasJohnGrinsteadwhoalsoplayedaveryimportantpartinmycareer.Butthenofcourse,ofmyownstudentsandpostdocs,afairnumberhavegoneontodowell,andhavebeengreattoworkwith.



A Ithinktherecordofanyuniversitydepartmentisbasedonitsresearchprofile.We’vetaughtalotofstudentsandalotofstudentshavegoneontomakesignificantnamesforthemselves,buttheactualrankingpartisdoneontheUniversity’sresearchrecord.TherehavebeenafairnumberofFRSsandothersuccesses,includingsignificantgrantsandforexample.Howeverifoneisjustthinkinginresearchterms,Bristolisinthetopfourorfivebiochemistrydepartmentsinthecountry,ithasbeenforsometimeandwillcontinuetobe.

Q What are you most proud of?

A IfIhadtochooseasingleevent,itwouldbebeingmadeanFRS.Inresearchtermstherehavebeentwomainthings.FirstlyIhadaverygoodPhDstudent,JohnTaylor,whowasbrilliantinthelab.WewereworkingonanenzymecalledEcoRVthatcutsDNAatoneparticularsequenceandnowhereelse,soweexpectedtheproteintobindtothatonesequenceonly.IaskedJohntodosomebindingmeasurementsandhekeptproducingthesameresult.HisresultsshowedthattheenzymewasbindingallthewayalongtheDNA,notjustattheexpectedsite,andeverywherewithexactlythesameaffinity.SoIsenthimbacktodoitagain,stupidly,andhedidittimeandtimeagain.EventuallyIrealisedthathewastellingmethetruthanditendedupbeing,atthetime,animportantdiscovery.ItshowedthatitisonlywhenrestrictionenzymesactuallygettotheirtargetsequencethattheyactivatethemselvesfortheDNAcleavagereaction.

Theothermaineventthatcomestomindwasafewyearslater.AcolleagueintheUSA,IraSchildkraut,suggestedweshouldworkonanotherenzymecalledSfiIbecauseithadaveryunusualtargetsequence.Againweputastudentontothisproject,LoisWentzell.WehadnoDNAinthelaboratorywithonlyonecopyofthetargetsequence,theonlyDNAwehadhadtwocopies.LoispurifiedtheproteinanddidherassayswiththisDNAwithtwotargetsites.Youwouldexpecttheenzymetocutatonesiteandthencomebackandcutattheothersite,butwhattheenzymedidwastocutatbothsitesatthesametime.Youcouldseethatfromtheveryfirsttestweran.Thisturnedouttobethestartoftwoquitebig

stories–proteinsactingattwoDNAsitessimultaneously,andDNAloopinginteractionswheretheproteinbindstwobitsofDNAatthesametime.

Q Have you had many fun moments over the years?

A Ohplentyofthose.NotmanyofwhichIcanrepeatinpublic!Practicaljokeswereprettycommon;mystudentsplayedmostofthemonme.

Q Could you give an example?

A Inthegoodolddaysyouusedtobeabletosmokeinthelab,andIusedtohaveacigarhabit.SoIwouldsmokealittlecigar,letitgooutandthenlightitupagainlateronandcarryon.MyfirstPhDstudent,whoisnowHeadofBiologicalSciencesatUEA,decidedasajoketotakemyunlitcigarandpushamatchupinsideandsowhenIcametolightitup,ofcoursethematchexploded.Everyoneelsefounditveryamusing.

Q What would your advice be for this year’s first-year biochemists?

A It’sdifferentfromwhenIwasafirst-yearstudent.Itdependsverymuchonwhereyouseeyourlong-termcareerheaded,rememberonlyafractionofourstudentsendupinresearch,somyadvicetothosewouldbetogetthebestlabtotakeyou.Youcan’tmakehardandfastrulesaboutwhatfirst-yearsshouldbedoing,becausesomanyendupindifferentfields.


Steve came to Bristol as a student in 1964 and received a BSc in Biochemistry in 1967. He went on to obtain a PhD and after spending a few years in the States returned to Bristol. Following some time as postdoc, became a junior lecturer, then a full-time lecturer, and subsequently a professor. He was elected a Fellow of the Royal Society in 2004.

Interview with…

Steve Halford

The record of any University department is based on its research profile… we’ve taught a lot of students and a lot of students have gone on to make significant names for themselves… Bristol is in the top 4 or 5

departments in the country, it has been for some time, and will continue to be.

The elucidation of the double helical structure of DNA, by James Watson and Francis Crick in 1953, was one of the key findings of the twentieth century, paving the way for virtually all modern biochemistry.

Intheearly1950stherewerevarioustheoriesaboutthestructureofDNA,includingtriplehelicesandinside-

outversionsoftherealthing,butnoneofthesefittedthedatainawaythatseemedplausible.Beforecomputersbecamepowerfulenough,thebestwaytoteststructuraltheorieswastobuildphysicalrepresentationsusingmetalmodels.WatsonandCrickdecidedtotackletheDNAstructureprobleminthiswayandaskedtheworkshopintheCavendishLaboratoryinCambridge,wheretheyworked,tomakethosepartsthatwerenotalreadyavailable.Theythenusedtheavailabledata,suchastherelativeproportionsofthe

individualcomponents,anddatafromRosalindFranklin’sX-rayexperiments,tobuildvariousstructures.Theonethatmadebothchemicalandbiologicalsensewasthe,now-famous,doublehelix.

Thisiconicmodelisperhapsthebestrecognisedrepresentationofabiologicalmoleculeinthehistoryofscience,andwasimmortalisedalongsideitscreatorsinafamousphotographbyAntonyBarrington-Brown.Byastrangetwistoffate,thismodelsubsequentlyspentmanyyearshousedwithinBiochemistryatBristol.WhenthefledglingDepartmentofBiochemistrywasestablishedattheUniversityofBristol,manyofitsfoundingmembersofstaffwererecruitedfromCambridge.ThisincludedDrHermanWatson(norelationtoJames!)in1968.HermanWatsonwasaproteincrystallographerwhohadlearnedhistradefromtheNobellaureateMaxPerutzatthenewlyestablishedLaboratoryofMolecularBiology(LMB)inCambridge.X-raycrystallographywasatechniquewhichhadonlyrecentlybeenappliedtoproteins,andbothexpertiseand

The Bristol DNA double helix


associatedequipmentwereinshortsupply.WhenHermanmovedtoBristol,understandablyhewaskeentobringwhateversurplusequipmentcouldpossiblybe‘spared’bytheLMB.Thisincludedseveraldrawersof,nolongerused,componentsformolecularmodels.IncludedinthismixwasWatsonandCrick’s,nowdismantledandabandoned,veryfirstmodeloftheDNAdoublehelix.

Themodelwasreassembledandformanyyearsitwasdiscreetlydisplayedatoneendofourundergraduateteachinglaboratory.Atquietmomentsduringthelongafternoonsofpracticalclasses,manyofourlecturingstaffwouldproudlyshowofftoourstudentsthishand-builtmodelwithitsoriginalscribblingsonthetin-platebasepairs.TheseviewingswereinvariablyaccompaniedbyanincreasinglyexaggeratedstoryofthegreatheistbywhichBristolhadstealthilyremovedthisfamousmodelfromrightunderthenosesofCambridgecolleagues.

Butpossessionisonlynine-tenthsofthelaw.AsthefundamentalimportanceofWatsonandCrick’sseminaldiscoverybecameevermoreevident,theScienceMuseuminLondon

launchedahuntforthisiconicmodel.QuitehowthetraileventuallyledtoBristolisunknown–itisassumedwewerebetrayedbyoneofthosequietboaststoapracticalclassonadarkwinter’safternoon,inspiringanunforgettablememoryinaloose-lippedundergraduate.HowthenegotiationswiththeScienceMuseumwentisalsoamystery,sufficetosaytheydidmanagetoextractmostoftheoriginalmodelwhichisnowondisplayinLondonandviewedbynearlythree-millionvisitorsannually.

Nonetheless,Bristolsomehowheldontotwosetsoftheoriginaltin-plate,hand-cut,basepairsandthesehavebeenincorporatedintoourown(partial)replicaoftheveryfirstmodeloftheDNAdoublehelix.Tocelebrateour50thanniversary,themodelwascompletelyrenovatedandprovidedwithanewdisplaycaseinsummer2013.Itstillsitsatthefrontofourfirst-yearteachinglaboratory,andisrepeatedlyshownofftopotentialnewstudentsatopendays.Itslocationintheteachinglabmeansthatthisinspiringmodelcancontinuetoprovideourstudentswithabeautifulandunforgettablelinktooneofthegreatestdiscoveriesinbiochemistry.


When the fledgling Department of Biochemistry was established at the University

of Bristol, many of its founding members of staff were recruited from Cambridge

To celebrate our 50th anniversary, Watson and Crick’s very first model of the DNA double helix was completely renovated and provided with a new display case in summer 2013

Reconstructing the DNA model.

Biochemistry at Bristol, past and present

The following articles have been written by members of the School. They address both key scientific findings and research which has taken place

at the University of Bristol and also some of the current areas of work. The full articles can be viewed at: bristol.ac.uk/biochemistry

Emily Coyte and Gus Cameron with the reconstructed DNA double helix in front of a picture of Crick and Watson with the original model.

Leo Brady, Gus Cameron and Emily Coyte


Allthreeoftheirresearchgroupscontainedresearchstudentsandex-researchstudents

thatweretobecomemembersofacademicstaffherewithinafewyears.TheseincludedGeorgeSchofield,DickDenton,ChrisPogson,PaulEnglandandSteveAshcroftwithRandle,TonyCroftsandJohnMcGivanwithChappell,andDavidYateswithGarland.Researchwasfundedbysubstantiallong-termfundingfromtheMedicalResearchCouncilandfromtheBritishDiabetesAssociation(nowcalledDiabetesUK).ThesetwofundersremainedhugelyimportantinthefundingofmetabolicresearchinBristol,andmuchofthisresearchhasbeenrelatedtodiabetes.Anotherthemehasbeenthestudyoftheregulationofintra-mitochondrialmetabolismcoveredelsewhereinthisvolume.

Inthefirst12yearsofBiochemistryatBristol,majoradvancesweremadeintheunderstandingoftheregulationofmammalianmetabolism,whichestablishedtheDepartmentasacentre

forsuchresearch.Highlightsincluded:detailedstudiesonthemetabolismoftheheartthataccompanieddifferentfuelsandworkloads(Randle,England,Denton);glucosestimulationofinsulinsecretionfrompancreaticbeta-cellsshowntorequiretheintracellularmetabolismofglucoseandincreasesinATPconcentrations(Ashcroft,Randle);

advancesintheunderstandingoftheroleofphosphorylationintheregulationofheartcontractileproteins(England);andtherecognitionthatinsulinstimulationoffattyacidsynthesisinfatcellsinvolvedtheactivationofpyruvatedehydrogenaseandacetyl-CoAcarboxylase(Denton,Halestrap).

TheregulationofthepyruvatedehydrogenasecomplexbecameamajorareaofresearchforbothDentonandRandle.Thesestudiesuncoveredagreatdealabouttheregulationofthephosphataseandkinaseenzymesinvolvedintheinterconversionoftheactiveandinactiveformsofpyruvatedehydrogenase.Inparticular,thephosphatasewasshowntobeactivatedbymicromolarconcentrationsofcalciumions.Duringthisperiod,RandlewontheMinkowskiPrizeoftheEuropeanAssociationfortheStudyofDiabetes(1966),andlatermanyotherhonoursincludingFRS(1983),Knighthood(1985)andFMedSci(1995).AshcroftwasawardedtheMinkowskiPrize(1979).

AfterthedepartureofRandleandAshcrofttoOxfordin1975,metabolicresearchinBristolwassoonunderpinnedagainbylong-termsupportfromboththeMRCandBDA(toDenton).StudiesbythegroupsofEngland,andlaterChrisProud,mademajoradvancesintheunderstandingofproteinphosphorylationinthe


regulationofmusclecontractionandproteinsynthesisrespectively.TheresearchofDentonandhisgroupconcentratedonunderstandingthemechanismofactionofinsulin,particularlyinfatcells.

Findingsoverthenext20yearsorsoincludedmuchevidencethatinsulinsignallinginvolvedtheactivationofintracellularproteinkinasesresultingintheincreasedphosphorylationofimportantproteinsincludingacetyl-CoAcarboxylaseaswellastheactivationofproteinphosphatases,whichledtothedephosphorylationofotherproteinssuchaspyruvatedehydrogenase.ImportantcolleaguesinthesestudiesovertheyearswereRogerBrownsey,GrahamBelsham,JeremyTavaré,KellyMouleandKateHeesom.Denton,mainlywithJimMcCormack,alsoestablishedtheroleofcalciumionsinintramitochondrialmetabolismfollowingtheirfindingthattwootherimportantintramitochondrialdehydrogenases(NAD-isocitratedehydrogenaseandoxoglutaratedehydrogenase),inadditiontopyruvatedehydrogenase,wereactivatedbymicromolarconcentrationsofcalciumions.

TheparallelactivationofthethreeintramitochondrialdehydrogenasesbycalciumionswasshowntobeanimportantmeanswherebyATPsynthesiswasenhancedinstimulatedcellswithouttheneedforanychangeinATPconcentration.AndrewThomasandGuyRutteralsomademajorcontributionstotheunderstandingoftheregulationofthecalcium-sensitiveintramitochondrialdehydrogenasesincludingsomeoftheearliestmeasurementsofincreasesincalciumionconcentrationswithinmitochondriaofstimulatedcells.Dentongavethe

LawrenceLectureoftheBDAin1981andwaselectedtoFMedSciandFRSin1998.

Inthemid1990s,undertheinfluenceofTavaré,RutterandPeterCullen,thecharacterofresearchinthisareachangedwithemphasisonintracellularsignallingpathwaysandtheintroductionofafullrangeofmoleculargenetictechniquesandreal-timecellimagingusingmainlyconvocalmicroscopy.ThelatterhadbeenintroducedbySchofieldandChappellbutwasgreatlyfacilitatedbytheadventoftheBristolImagingFacility,fundedbyagrantfromtheMRC.Importantadvancesinvolvingreal-timeimagingincluded:demonstrationoftherapidtransferoftheglucosetransporterandotherproteinstothe

plasmamembraneincellsexposedtoinsulin(Tavaré);measurementofchangesinmitochondrialcalciumionconcentrationsinbeatingheartcells(ElinorGriffiths,Rutter);detailedstudiesonthemovementofinsulin-containinggranulestogetherwithassociatedchangesintheconcentrationsofATPandcalciumionsinpancreaticbetacellsinitiatedbyglucosemetabolism(Rutter);andinvestigationsintotheimportanceofinositolphosphatesandphosphoinositidesinintracellularsignalling(Cullen).TheseandassociatedstudiesresultedinTavaregivingtheLawrenceLectureoftheBDAin2000,RutterwinningtheMinkowskiPrizeoftheEASDin2004andCullengivingtheMortonLectureoftheBiochemistrySocietyin2010.

Bristol Regulation in Metabolism Group 1989. From left to right: F.Doyle, T. Diggle, K. Moule, G.Rutter, S.Cramer, A.Borthwick, J.Taveré, G. Welsh, J. McGivan, M.Dickens, D. Denton, M.Leake, H.Mellor, C.Proud, N. Redpath, C. Schmidt-Peiffer, A. Halestrap, C. MacLennan, N. Edgell, R. Poole, N. Price.

The laboratory had the catchy name of M101 with M referring to the fact it was a mezzanine floor. It was destined to become the centre of metabolic research in the Department until the Integrated Signalling Laboratories opened in early 2001

M101 was not the only laboratory in the Department in which the regulation of mammalian metabolism was studied, but it was the focus for this research for over 30 years

The regulation of metabolism

The study of the regulation of mammalian metabolism at Bristol got off to a flying start with

Philip Randle, Brian Chappell and Peter Garland.

Dick Denton

Philip Randle, taken around the time he was elected FRS (1983).

isnowbeingdeployedagainstmanyinfectiousdiseasesthatplaguethedevelopingworld.Together,inthemid1990sLeoandHilarymodernisedmuchoftheinfrastructureforstructuralbiologyresearchinBristol,untilHilary’sretirementin1997.HilaryhasremainedinBristolsinceandnowformsaverywelcome,butinsufficientlyfrequent,visitortoBiochemistry.

HilarywasreplacedbyAndreaHadfieldwhoalsotappedintolocalenzymologyinterestspursuingtime-resolvedstudiesofaspartatesemialdehydedehydrogenaseand,onceagain,glyceraldehyde-3-phosphatedehydrogenase.Duringtheearly2000sBristolstructuralbiologyalsobenefittedfromaveryconvenientdecisiontobuildthenextUKsynchrotronjustdowntheroadinDidcot.TheDiamondLightSourcenowformsapremierresourceforproteincrystallographyanditsnearbylocationhastransformedstructuralbiologyresearchinBristol.AlthoughAndrealeftin2010,PaulRacehassincejoinedtheSchoolandisnowveryactivelypursuinganexpanding

programmeinpolyketidesynthasesandtheirapplicationinsyntheticbiology.ThisalsocomplementsLeo’smorerecentworkonsyntheticproteins,withDekWoolfsoninChemistry,alongwithalong-standinginterestincellsurfaceadhesionproteins.Asthedeterminationofproteincrystalstructureshasbecomemuchquicker(althoughnolessunpredictable)manyotherresearchersatBristolhavealsobeguntodabbleinstructuredetermination.InvaryingdegreesofcollaborationwithLeoandPaul,theseincludeRossAnderson,IanCollinson,TonyClarke,MikeJonesandRichardSessions.

Proteincrystallographyremainsatrulycross-disciplinaryfieldinwhichpractitionersneedtocombineskillsinmolecularbiology,biochemistry,chemistry,maths,physicsandcomputing.Itisrareforasingleindividualtobeanexpertinall.Thefieldisthereforeunusuallyreliantonteamwork.Alloftheconsiderableachievementsduringthelast45yearsofstructuralbiologyresearchatBristol

wouldneverhavebeenpossiblewithouttheskillsanddedicationofthegraduatestudentsandpostdoctoralresearchersthatformedtheWatson,Muirhead,Brady,HadfieldandRacegroups.Itispleasingthatsomanyofthemhavegoneontoexcellenceintheirfurthercareers,andamonumenttotherigourthatinfusesallresearchinBiochemistryatBristol.

Structural Biology at Bristol: a brief history

Atthattime,proteincrystallographywastheonlywayinwhichdetailedpictures

couldbeobtainedoftheexquisiteatomicarrangementsthatdeterminedthepropertiesofproteins.Intheearlysixtiesthiscomplextechniquehadbeenextendedtoproteins,leadingtothebreakthroughdeterminationsofthestructuresofmyoglobinandhaemoglobinbyJohnKendrewand

MaxPerutzrespectively,andforwhichtheywereawardedtheNobelPrizeinChemistryin1962.Interestingly,JohnKendrewhadbeeneducatedinCliftonCollege,Bristol.KendrewandPerutzwerethefirsttwomembersoftheMedicalResearchCouncilUnitattheCavendishLaboratoryinCambridge,theprecursortothenowfamousMRCLaboratoryofMolecularBiology.ItwasherethatFreddieGutfreundturnedtorecruitstafftoestablishstructuralbiologyatBristol.TwoemergingscientistsfromtheKendrewandPerutzlaboratories–HermanWatsonandHilaryMuirhead–wereselectedandenticedtoBristolin1968and1969respectively.TogethertheyestablishedproteincrystallographyfromscratchinBristol.ThiswasinitiallywithinthemolecularenzymologylaboratorylocatedintheInnerCourtbuildingonWoodlandRoad,andlatermovedtotheMedicalSchool.HermanandHilaryformedanimmenselyproductivepartnershipandweretoworktogetherinBristolfor26years.

Inthedaysbeforerecombinantproteinproduction,thelargequantitiesofpurifiedproteinsrequiredforastructuraldeterminationhadtobeobtaineddirectlyfrombiologicaltissues.HermanandHilaryquicklyrealisedthatscientistsattheBristolVetSchoolalreadyhadaccesstosuchproteinsourcesinthefleshofcows,pigsandsheep.Thisconvenientresourcewasquicklymatchedupwithlocalenzymologyinterestsandaprogrammeindeterminingstructuresofmostofthekeyglycolyticenzymesresulted.ThesestructureswerefundamentaltounderstandingenergyderivationwithinlivingorganismsandtheirassociationwithBristolwasasubstantialcontributortotheemerginginternationalreputationenjoyedbytheBiochemistryDepartment.

UsingbothlocalX-raygeneratorsandtheDaresburySynchrotronRadiationSource,inCheshire,HermanandHilarytookthousandsandthousandsofX-rayimagesonfilmaspartofalaboriousandcomplexprocessby

whichthemoleculardetailsofaproteincrystalcouldbedetermined.Thisalsorequiredsubstantialcomputingpowerandhenceexpertiseinprogrammingwasalsoessential.Singlestructurescouldtakeyearstoresolve.OvernearlyaquarterofacenturytheproteinstructuresthatemergedfromBristolincludedanalmostcomplete

‘Who’sWho’ofglycolyticenzymes:D-glyceraldehyde-3-phosphatedehydrogenase,3-phosphoglyceratekinase,fructose-bisphosphatealdolase,phosphoglyceratemutase(allfromHerman’sgroup),andglucose6-phosphateisomerase,pyruvatekinase,lactatedehydrogenase,andovotransferrin(allfromHilary’sgroup).Manyofthesestudiesreliedonclosecollaborationswithothergroups–suchasthoseofBobScopesattheVetSchool,andJohnWilliamsandJohnHolbrookintheMedicalSchool.Theimmenseinvestmentsoftimeandexpertiseineachofthesestructureswereachievedbyassemblingteamscomprisingsomeverytalentedresearchers.Althoughitisdifficulttosingleoutindividuals,someofthosewhotrainedandworkedwithHermanandHilaryincludedDaveStammers,DaveStuartandDaveShotton(nowallinOxford),ChrisDavies(MUSC,USA),SteveGamblin(NIMR),GideonDavies(York),DaleWigley(CRUK)andJennyLittlechild(Exeter).ItisremarkablethathalfoftheseformerlabmembersarenowFellowsoftheRoyalSociety.In1993HermanWatsonretiredand,verysadly,diednotlongafter.ThiswasagreatlossforBristolBiochemistry.Hewasreplacedin1994byLeoBrady,whobroughtahistoryofHIVresearchwithhimfromYork.Inadditiontotheseinterests,itwasnotlongbeforehetoobecameinvolvedinBristolmolecularenzymology.WithJohnHolbrook,thestructureoflactatedehydrogenasefromPlasmodiumfalciparum(thecausativeagentofmalaria)wasdetermined,andthisthenformedthebasisforasubstantialdrugdevelopmentprogramme.This,incidentally,wasoneoftheveryfirst‘public-private’partnershipsfordevelopingnewdrugs,amodelthat


A picture tells a thousand words. This must have been self-evident to the early founders of molecular enzymology at Bristol, Freddie Gutfreund and David

Trentham, as a priority in the early days of the Department was to make appointments in the then emerging field of protein crystallography.

Immense investments of time and expertise were achieved by assembling teams comprising some very talented researchers

The considerable achievements during the last 45 years of structural biology research at Bristol would never have been possible without the skills and dedication of the graduate students and postdoctoral researchers

Top left to bottom right:Glucose 6-phosphate isomerase, 1976;Glyceraldehyde 3-phosphate dehydrogenase, 1982;Human Aldolase, 1991;Pyruvate kinase, 1996;Plasmodium falciparum lactate dehydrogenase, 1996.

John Kendrew and Max Perutz were awarded the Nobel Prize in Chemistry in 1962

25 years of glycolytic enzyme research in Bristol…

Leo Brady

Philip Randle brought two rising stars in mitochondrial research, Brian Chappell and Peter Garland, when he moved from Cambridge to establish Biochemistry at Bristol in 1964.

BrianwasoneofthefirsttoacceptPeterMitchell’sChemiosmotictheoryand

thisunderpinnedhisgroundbreakingresearchonmetaboliteandiontransportacrossthemitochondrialinnermembrane.Peter’sresearchfocusedonmitochondrialfattyacidandcitricacidcyclemetabolism.TheyeachreceivedtheprestigiousBiochemicalSocietyColworthMedal,in1965and1968respectively,withPeterleavingforDundeein1971.BetweenthemtheytrainedmanyPhDstudentsandpostdoctoralworkers,severalofwhomweretomaketheirownmarkonthefieldofmitochondria,transportandbioenergetics.TheseincludedDavidNicholls,MartinBrand,PeterHendersonRichardHansford,JohnMcGivanandTonyCrofts.

TonyandJohnestablishedtheirownresearchgroupsintheDepartmentwithTonybecomingaworldleaderinphotosynthesis,andJohndevelopinghisinfluentialstudiesonaminoacidtransportandmetabolism.SeveralofTony’sstudentsandpostdocsthemselvesbecamemajorplayersinthefieldofbacterialphotosynthesisincludingBazJackson,RogerPrinceandRichardCodgell.

Towardstheendofhisacademiccareer,Brian,togetherwithLydiaHenderson,workedcloselywithOwenJonesonsuperoxideproductionbyNADPHoxidaseinneutrophils.Owen’smajorresearchinterestwasmetalloporphyrinsynthesisandbacterialphotosyntheticelectrontransportsystemsandthesestudieswerecomplementedbytheresearchof

TrevorGriffithsonchlorophyllsynthesisandPaulWoodonmicrobialelectrontransportchains.OneofOwen’sPhDstudents,NeilHunter,wentontomakemajorcontributionstothefieldofphotosynthesis,becomingaFellowoftheRoyalSociety.Today,studiesonbacterialphotosyntheticelectrontransportarecontinuedintheSchoolbyMikeJones.

AtthesametimeasmitochondrialstudiesflourishedinBrian’slaboratory,themetabolicresearchgroupheadedbyPhilipRandlewasbecomingincreasinglyinterestedintheregulationofmitochondrialmetabolismandespeciallypyruvatedehydrogenase.Thiswork,andhowitdeveloped,isdescribedinthearticleWHEREbyDickDenton.In1973,oneofDick’sPhDstudents,AndrewHalestrap,discoveredapotentandspecificinhibitorofthepreviouslyunidentifiedmitochondrialpyruvatecarrierandtheplasmamembranelactatetransporterwhich


laidthefoundationofhisownresearchcareerinBristol.Hehascontinuedhisstudiesonthemitochondrialandplasmamembranepyruvateandlactatetransporters,makingmajorcontributionstotheircharacterisation,identification,structure,mechanism,metabolicroleandregulation.Hehasalsomadeimportantcontributionstoourunderstandingoftheroleofmitochondriainthehormonalregulationofgluconeogenesis,includingelucidatingthemechanismofactionoftheantidiabeticagentmetformin.

MorerecentlythefocusofAndrew’sresearchhasbeenonthemolecularmechanismmitochondrialpermeabilitytransitionpore(MPTP)and,withElinorGriffiths,itsroleinischaemia/reperfusioninjuryoftheheartandasadrugtargetforcardioprotection.

AndrewwaselectedaFellowoftheAcademyofMedicalSciencesin2008andawardedtheKeilinMedaloftheBiochemicalSocietyin2010.Inmorerecentyears,theresearchofothersmembersoftheSchoolhastakenonamitochondrialslantincludingJonLane(mitophagy),JeremyHenley(regulationofmitochondrialfusionandfissionbysumoylation)andNigelSaveryandMarkSzczelkun(mitochondrialDNAreplicationandtranscription).MikeTannerjoinedtheDepartmentin1970andstartedhisground-breakingworkonthestructureoftheerythrocyteanionexchanger.HisresearchbroadenedtoincludeothermajormembraneproteinsincludingtheRhesusproteinsandglycophorins.Theimportanceofredcellmembraneproteinsindefiningbothmajorbloodgroupsandrarevariantsledtoa

long-standingcollaborationwithDaveAnsteeintheBloodTransfusionService(nowNHSBT).Mikeretiredin2004buthisworkiscontinuedbyhisformerpostdocsLesleyBruce(nowatNHSBTBristol)andAshToye.AshwasawardedtheRaceandSangerawardin2013bytheBritishBloodTransfusionSociety.MiketrainedupmanyotherPhDstudentsandpostdocswhowentontodeveloptheirownsuccessfulcareersinmembraneproteinbiochemistryincludingSteveHigh,ChrisTate,MarkYoungandMarkParker.

PlasmametabolitetransportersarealsoafocusofPaulaBooth’sgroupwhichstudiesthemechanismsunderlyingthefoldingofmembraneproteinsincludingtheroleofthemembranelipids.PaulawasawardedaRoyalSocietyWolfsonMeritAwardin2008andaprestigious

ERCSeniorInvestigatorAwardin2013.PaulCurnow,aformermemberofPaula’sgroup,isstudyingthebiochemicalandbiophysicalpropertiesofthenovel12transmembranehelixsilicontransportersofdiatoms,unicellularalgaethatsheaththemselvesinanintricateoutercellwallmadeofsilicaglass.HewasawardedaBiochemicalSocietyEarlyCareerResearcherAwardinBioenergeticsandMetabolismin2009andisnowfundedasanindependentResearchFellowbyaprestigiousERCGrant.

Thefullarticlecanbefoundatbristol.ac.uk/biochemistry/50th_anniversaryanddetailsofallcurrentresearchonmitochondriaandtransporterscanbefoundatbristol.ac.uk/biochemistry.


Mitochondria, bioenergetics and metabolite transport

In more recent years, as interest in mitochondria has grown because of their role in cell signalling and cell death

The study of metabolite and ion transport across mitochondrial membranes initiated by Brian Chappell was soon complemented by studies on their transport across the plasma membrane

Andrew Halestrap

Helix-3

Helix-6

F360

K38

K45 K282 DIDS

K413

500 nm

10 um

Electron micrograph of mitochondria in a beating rat heart rapidly sampled with a biopsy gun followed by cryofixation using high pressure freezing (Data from Prof Halestrap’s laboratory obtained by Joke Ouwendijk Tatyana Andrienko and Paul Verkade).

Mitochondria in an isolated isolated heart cell labelled specifically with a fluorescent dye and visualized with confocal microscopy (Data from Prof Halestrap’s laboratory obtained by Andreas Rossbach).

The proposed structure of the lactate transporter (MCT1) present in many cancer cells with an inhibitor (DIDS) bound to the external surface. This structure was developed using “homology modelling” by Dr Richard Sessions based on extensive experimental work within Professor Halestrap’s laboratory.

Chrissy Hammond: Modelling osteoarthritis in Zebrafish

Osteoarthritisisapainfuljointconditionwhichisbecomingincreasinglyprevalentasa

resultofanagingpopulation.Lossofprotectivecartilagefromalifetimeofwear-and-tearanditsectopicreplacementwithbonemattercausestherubbingofbone-on-bonewhichcanmakenormalmovements,suchasgettingoutofbedorputtingthekettleon,verypainfulexperiences.Whiletwinstudieshavedemonstratedastronggeneticcomponenttoosteoarthritis,theidentityandeffectsofthesegenesareonlyrecentlybeingexamined.UsingZebrafishasavertebratemodel,theHammondlabaimstounderstandmoreaboutthisconditionsufferedbytensofmillionsofpeopleworldwide.

Theonsetofosteoarthritisinmanywaysresemblesthenormalembryonicprocessofendochondralossification,wherebybonesdevelopfromacartilagetemplate.Thecartilagecellsproliferate,turnhypertrophicthendie,leavinggapsforthebonecellstomigrateinto.Wearing-awayofcartilagereinitiatesthisprocessasarepairmechanism,butthedeathofthecartilagecellsandinfiltrationofboneexacerbatesosteoarthritis.Understandingthegeneticcausesofthenormaldevelopmentisanimportantstepinunderstandinghowtoterminateitatthehypertrophicstage–maintainingthebenefitsofthecartilage

repairwhileensuringitdoesn’tgetreplacedwithbonematter.

ThepopularityoftheZebrafishasamodelorganismreallytookoffinthe1980s.Itwaschosenforitsconvenientsmallsizeandlowmaintenancelivingconditions,geneticswhichareeasytomodulateand,crucially,transparentembryosmakingin vivovisualisationoftissuesastheydevelopincrediblyeasy.WorkdonebytheHammondlabhashelpedestablishtheZebrafishasavalidandadvantageousmodelorganismtouseinthestudyofosteoarthritis.

Theinitialproof-of-principlecamewhenthelabranageneticscreenonZebrafishdisplayingphenotypiccharacteristicsofosteoarthritissuchasreducedjointmobility,lossofcartilageandbonyspurformation.OneofthegeneswhichcameupwasCHST11,thehumanhomologueofwhichwassubsequentlyidentifiedasanosteoarthritissusceptibilitygene.Thelabisnowworkingtounderstandhowchangestothiscartilagematrixproteinleadtochangesincellsignalling.

Sincethen,thelabhasusedZebrafishtostudyanumberofothergeneswhichhavebeenimplicatedinhumanosteoarthritis,includingonecalledMcf2l.ThisproteinisknowntocausemigrationofsomecelltypesincludingbreastcancerandSchwanncells,butwhatroleitcouldplayinosteoarthritisisunknown.UtilisingthetransparentbodiesoftheembryosandmRNAin situhybridisation,thechangingpatternsofMcf2lexpressionduringdevelopmentwasshownforthefirsttimeinanyanimalmodel.ThelabfoundMcf2lhighlyexpressedindevelopingjawcartilage.Followingtheestablishmentofnormalexpressionpatterns,futureworkwillinvolveoverexpressionandknockdownstudiesofgeneslikeMcf2ltoseewhateffectthishasonjointdevelopment.

Thelabalsoseekstounderstandthecommunicationbetweencelltypesimportantincartilageandbonedevelopment,andwhateffectphysicalactivityandstrainmayhaveatageneticandcellularlevel.

Osteoarthritisissufferedby40%ofpeopleover70yearsoldandcanprogresstoadebilitatingextent.Whilesymptomscansometimesbemanagedorprevented,thereisnoknowncure.Theoriginsoftheconditionneedtobebetterunderstood.TheHammondlab’sworktowardsidentifyingandcharacterisingthegenesresponsibleforcartilageandbonedevelopmentaimstorevealsometargetswhichmayleadtoamuch-neededpharmaceuticalcure.

Ian Collinson: Protein secretory system

AtthetimeofthefoundingoftheBiochemistryDepartment,thetranslocationofproteins

acrossandintolipidmembraneswasanalmosttotalmystery.HowdoantibodiessynthesizedbyourB-cellsendupinourblood?Howdothecholeraandtetanusbacteriasecretetheirdeadlytoxins?Whilemany(correctly)reasonedthattheremustbespecialistcellularmachineryinvolvedinthiscomplextask,therewasoppositionwhobelievedittobeaspontaneousprocess.Atthetimetherewaslittleevidenceeitherway.

Alotofprogresshasbeenmadesincethen,withgeneticscreensandreconstitutionofmembranetransportin vitroconfirmingthatprotein-basedmachineryisindeedrequiredfortranslocation.Threemembrane-boundproteinswerefoundtocomprisethecorecomplex,whicharefoundin


almostallcellsofallorganisms.InE.coli,themoststudiedsystem,theyareknownasSecYEG.

Ian’sworkhasbeencentredonSecYEGsincehisPhD.UsingelectronmicroscopyattheMaxPlanckInstituteofBiophysicsinFrankfurtandX-raycrystallographyatHarvardhewasheavilyinvolvedwithsolvingthefirststaticstructuresofSecYEG.

WhenIanjoinedtheUniversityofBristolin2004,itwasknownthatSecYEGhasaclamshell-likestructure,designedtoopenaboutahingeandtherebyallowthepassageofproteinsthroughthecomplex.Secretoryproteinspassthroughthechannelcreatedbythispartitioningontheirwaytotheothersideofthemembrane.Thestructureofthecomplexalsoexplaineditscapabilityformembraneproteininsertion,throughalateralgateformedbetweenthetwohalvesoftheclamshell.Howeververylittlewasknownaboutthedynamicmechanismofproteinsecretionandmembraneproteininsertion,sowhenIanmovedtoBristolhedecidedtoplaytotheDepartment’sstrengthsofmolecularenzymologyandproteindynamicsandfocusontheinteractionsandbehaviourofSecYEGwithitssubstrateandotherproteinswhichaidtranslocation.

Structuralbiologystillplayedakeypartofthis.In2012theCollinsonlabsolvedthestructureofSecYEGandthefirstfewaminoacidsofaproteinabouttopassthroughthecentralpore.ThiswasthefirstvisualrepresentationofthestartoftranslocationandclearlydemonstratedsomeofthestructuralchangeswhichoccurinSecYEGtoallowproteinstotravelthroughthepore.

ThelabhasalsosoughttounderstandmoreaboutotherproteinswhichassistSecYEG,primarilySecA.ThisisamotorATPasewhichprovidesthepushingpowertogetthesubstrateproteinthroughthecentralporeofSecYEG.TheyhavemademuchprogressinunderstandinghowSecAisactivatedbyinteractionswithSecYEGandthemembrane,andhowitusestheenergyfrombreakingdownATPtoforcethetranslocatingproteinacrossthemembrane.SecAhasonlybeenfoundinbacteria,sothismayprovideausefultargetforfutureantibioticdevelopment(incollaborationwiththeDundeeDrugDiscoveryUnit).

Themechanismofproteintranslocationisstillfarfromsolved,sofutureworkwillrequirethecontinueddeploymentofclassicalbiochemicaland

biophysical,honedinBristolover50years,aswellasthedevelopmentofnewmethodssuchashigh-resolutionelectronmicroscopyandsinglemoleculetechniques.

Ross Anderson: Artificial enzyme design and assembly

Withproteinsaswithnovels,it’sonethingtounderstandandanothermatterentirely

tobeabletosuccessfullycreateyourown.Ourknowledgeofproteinsandtherelationshipbetweenstructureandfunctionhasimprovedsomuchinthepast50yearsthatwearerightnowatanexcitingtransitionbetweenunderstandingproteinstructureanddesigningourown.

FromTaqpolymeraseinPCRtorestrictionenzymesingeneticmodification,enzymeshavebeenusedoutsideoftheirnaturalcontextfordecades,buttherangeforutilityislimitedbywhatevolutiononthisplanethasgivenus.Enhancingthatrangewithnew,man-madeproteinshashugepotentialforhumanhealthandunderstanding.

Twooptionspresentthemselves:adaptsomeofthehugediversityofproteinsfoundinnature,orcreatecompletelynovelonesfromfirstprinciples.Naturalenzymesareexquisitemachinesevolvedovermillionsofyearstofillspecificnicheswithinalivingorganism.Aswellascorecatalyticroles,eachenzymemustbeabletointeractwithdozensofothermoleculesandrespondtomultiplesignalstoallowtheorganismtosurviveinachangingnaturalenvironment.Theseadditionalfeaturesareunhelpfulbaggagetothoseseekingtomanipulatetheenzymeforotherfunctions,butthehighinterdependenceofaminoacidswithinnaturalproteinsmakesmodificationverychallenging.Improvingoneaspectofenzymefunctioncouldeasilydestroyanother,perhapscausingittoaggregate.

TheapproachoftheAndersonlabusesanalternativeroute–notadaptingpre-existingenzymes,butdesigningthemfromscratchforeventualuseasdiverseandspecificcatalytictools.Theproteinstheyworkwitharecalledmaquettes;‘roughdrafts’offully-functionalnewenzymes.Thesearemostlybasedonsimplefour-helixbundleswheretheeachaminoacidhasasimpleandclearlydefinedrole,whichmayincludethebindingofcofactorsatthecentreofthebundle.Thetractabilityofeachaminoacidbestowcontroloverthemaquette’sfundamentalpropertiesinawaysimplynotpossibleinnaturalproteins.

Aswellassculptingthesemaquettesintoawiderangeoffullysyntheticenzymes,anexcitingchallengefortheAndersonlabisusefullyintegratingthemintolivingorganisms.Theyhavealreadysuccessfullydesignedamaquettewhichisexpressed,translocatedandpost-translationallymodifiedbynaturalmachineryofE.coli,convertinganon-covalenthemeBcofactorintocovalentlyligatedhemeC.Thiswasaphenomenalproof-of-conceptandthefirstexampleofaman-madeproteintobefullypackagedwithanaturalcofactorin vivo.Removinghemedissociationinthiswayhasgreatlyfacilitatedstudyofthemaquette’sstructureandpossiblefunctionswithanaimofeventuallysubstitutingthemintonaturalbiochemicalpathwayssuchasrespirationorphotosynthesis.

Themaquettesarecapableofbindingtwocofactorswithdifferentredoxpotentialssimultaneouslywhichpermitselectrontransferacrosstheprotein.ThelabhasdemonstratedthisinamaquettewithonehemeBandonehemeCwhichcouldbeincorporatedintoarespiratorypathway.TheyalsofoundthatreplacingtheironinhemeCwithzincproducedamaquettewithlight-activatedelectrontransfer,akeyprocessofphotosynthesis.Combiningthedesignofman-madeproteinswithefficientexpressionincellscouldopenuphugenewavenuesincludingimprovedtargetedtherapiesandenvironmentally-friendlyfuelsystems.


Some current areas of work at Bristol Biochemistry

Emily Coyte

Emily Coyte, Assistant Teacher in the school, profiles the work carried out by three current members of the academic staff.

nowembeddedinoursecondyearBiochemistryprogramme.

Steve’sresearchmadesignificantcontributionstoourknowledgeofthereactionsofproteinsonDNA;howtheyfindtheirtargetsitesonDNA;howtheycancatalysereactionsatonesequencewhilstexcludingallothers;andhowinmanyinstancestheytraploopsbybindingtwositesonthesameDNA.Numerouscolleaguesparticipatedhereandthephotographabove,fromSteve’sretirement,showsalmostallofhispostgraduateandpostdoctoralassociates.Steve’sworkwasrecognisedwiththeNovartisMedalfromtheBiochemicalSociety(2011)andelectiontotheRoyalSociety(2004).In1983,theUniversityofBristolstrengtheneditsresearchonnucleicacidsbyformingtheinter-departmentalUnitofMolecularGenetics,withseveralnewappointmentsacrossthelifesciences.TwoofthesewereinBiochemistry–BillChiaandLenHall.BillwasprimarilyinterestedindevelopmentalgeneticsbutwhileinBristolwaswaylaidbyTonyClarkeandDaleWigleyintousinghisexpertiseinmoleculargeneticstoenableJohnHolbrook’steamtocarryouttheirpioneeringstudiesinproteinengineering.BillmovedontoaresearchinstituteinSingaporein1991toworkuninterruptedlyondevelopmentwhereheadvancedthatfieldconsiderably.Len’sresearchareawasinthefertilisationofmammalianeggsbyspermbuthewastotakeonprogressivelymoredemandingadministrativeroles–asHeadoftheDepartmentin2000,FacultyDeanin2004andProVice-Chancellorin2008.TheHalfordandBrowngroupswereinitiallylocatedintheInnerCourtlaboratoriesoffWoodlandRoad,previouslythehomeofthemolecularenzymologylaboratory.However,theymovedin1985toasuiteofoldlaboratoriesintheD40-50corridoroftheMedicalSchool,tobringthemclosertoBacteriology.ThespaceleftbyNigel’sdeparturewaslateroccupied,from1995,byKevinGaston.

Kevin’sappointment,togetherwithSheelaJayaraman’sMRCFellowship(1996-2006),broughtnewadvancesintothisarea,expandingitfromitspreviousfocusonprokaryoticsystemstotheeukaryoticworld.Hisresearchprojectsincludedanalysesofgenecontrolinpapillomavirusandinleukaemiaandcancer.Theold-stylelaboratoriesinD40-50,smallroomswithwoodenbenchesseparatedbyanemptycorridor,werethankfullysweptawaywhenthecorridorwascompletelyrefurbishedin1999asanopen-planlaboratorytohousetheDNA-proteininteractionsunit.TheoldlaboratoriescanbeseeninthebackgroundofthephotoofKevin’sgroup,aboveright.

ThethreemostrecentappointmentsinnucleicacidbiochemistrywereallconnectedinsomewaytoSteveHalford.Firstly,MarkSzczelkunhadbeenapostdocwithStevefrom1994,wherehehadcarriedoutground-breakingworkinDNAloopingbyrestrictionenzymes.HethenobtainedaWellcomeTrustCareerDevelopmentAward(1998)followedbyaSeniorFellowship(2002)beforehiscurrentstaffappointmentsasreader(2007)andprofessor(2010).NigelSaverycameherebyadifferentroute,initiallyasatemporarylecturertofulfilHalford’steachingandadmindutieswhilstSteveheldaResearchLeaveFellowship.ItsoonbecameapparentthatNigelwasfulfillingtheserolesfarbetterthanHalfordeverdid,sothepostwasquicklymadepermanent,whichinturnallowedNigeltofurtherhisresearchontranscription.ThatpostrecentlyevolvedintoaChair(2014).MarkDillinghamhadeven

earlierconnections–whilehewasanundergraduateatBristol(1993-96),Halfordwasthepersonaltutorresponsibleforhisfirstyeartutorials.Atthisyear’s50thanniversaryoftheBiochemicalSocietyColworthMedals(whichDillinghamhadbeenawardedin2010),Markcommentedthathis‘first-yeartutorialshadintroducedhimtothewondersofDNA-proteininteractionsbutprettymuchattheexpenseofallotheraspectsofthecourse’.ThismayexplainwhyDillinghamwentontoasummerstudentshipwithSzczelkunandhisfinal-yearprojectwithGaston.AfterhisPhDandpostdoctoralresearchwith,amongothers,DaleWigleyandMartinWebb(bothBristolalumni),DillinghamreturnedtoBristol,initiallyasaRoyalSocietyURF(2005-12)beforetransferringtopermanentstaff.TheColworthmedalisforthetopbiochemistagedunder35,andDillingham’sawardwastheappropriaterecognitionforhisworkonDNAhelicases.Szczelkun,SaveryandDillingham,shownbelow,formtogetheracohesiveunitinDNA-proteininteractionsasallthreearepresentlystudyingrelatedsystems–DNAmotorproteinsthatutiliseATPenergytotranslocatealongDNApriortomediatingkeyreactionsintheinterrelatedfieldsofDNArepair,replication,restrictionandtranscription.TherecentstudiesthusextendtheworkonATP-dependentenzymesthathasbeenafocusofBristolBiochemistryforthepast50years.Indeed,howproteinsutiliseATPenergywasinlargepartelucidatedherebyDavidTrentham,workingwithFreddieGutfreundintheearly1970s.

Many of the founding figures of Biochemistry in Bristol came from Cambridge and one of these was present at the birth of nucleic acid biochemistry.

FreddiemovedtoBristolwhentheDepartmentbeganandcontinuedhisverysuccessful

researchcareerhere.Hisfieldwasproteinbiophysics,thoughFrancisnotedthisas‘Freddie’sredherring’onthegroundsthattheinstructionsfortheproteinwerealreadylaiddownintheDNA!TheoriginalWatson-CrickmodelwaslaterfoundlanguishinginthebasementofCambridgePhysicsand,asnotedinthisvolume,wasbroughttoBristolbyanotherémigréfromCambridge,HermanWatson.

NucleicacidresearchinBristolstartedshortlyafterBiochemistrywasfounded,withthearrivalofJohnHindleyin1968,fromFredSanger’slaboratoryinCambridge.Atthattime,SangerwasbetweenhistwoNobel-winningprojects,proteinandDNA

sequencingandwastryingtosequenceRNA.PerhapsJohn’smostfamousresearchcameshortlyaftermovingtoBristol,inacollaborationwithCharlieWeissmanninZurichonaviruswithanRNAchromosome.JohnadvancedSanger’smethodssufficientlytoobtainasequenceof175basesfromtheviralRNA,amassiveachievementatthetime(1970).Meanwhile,Weissmanndeterminedtheaminoacidsequenceofthecorrespondingprotein,andwhenlineduptheirtwosequencesrevealedoneofthefirstvalidationsofthegeneticcodeinreallife.Universityexpansioninthe1970sallowedfortwomoreappointmentsinnucleicacidbiochemistryin1976–NigelBrownandSteveHalford,shownbelow(leftandrightrespectively,atplay).Nigel,likeJohnHindley,came

fromSanger’sgroup,butinalatererawhenDNAsequencinghadbecomepracticable.WithSanger,Nigelcontributedtothefirstgenomesequence,aviralchromosome5375baseslong.Nigel’sfirstobjectiveinBristolwastosequenceatransposableDNAelementthatconferredresistancetomercury,anelementalsobeing

studiedatthattimebyJohnGrinstedandMarkRichmondinwhatwasthentheDepartmentofBacteriology.Nigelwentontocoverthegeneralprocessingoftoxicmetalsinbacteria,thoughhemovedin1989totheChairinMicrobiologyattheUniversityofBirmingham.Nigel’slatercareerfollowedadministrativepathways,asDirectorofScienceattheBBSRCandasHeadofScienceandEngineering,andthenSeniorVice-Principal,attheUniversityofEdinburgh.HewasawardedanOBEforservicestoscienceinthe2014NewYear’sHonours.

Conversely,SteveHalfordstayedinBristolthroughouthiscareer–asanundergraduateinthesecondsetofstudentstodoBiochemistryinBristol(1964-67);asapostgraduatewithFreddieGutfreund(1967-70);asapostdocwithFreddieandMarkRichmond(1972-76);andthenstaffappointmentsaslecturer(1976),reader(1989),professor(1995)throughtoanemerituspostonhisretirementin2011.Steve’sresearchasaPIfocussedprimarilyonrestrictionenzymes,wherehedeployedwhathehadlearntaboutenzymesfromFreddieandwhateverheneededtoknowaboutDNAfromNigelandJohnGrinsted.Someyearslater,JohnandStevesetuptheMolecularGeneticsIIcoursethatis


Research on nucleic acids

Steve Halford

This photograph shows Freddie Gutfreund (centre) walking through Cambridge in the company of his close friends Francis Crick (right) and Jim Watson (left). It dates from 1952 and one year later Watson and Crick

published the DNA double helix.

Overthelast50yearstheBiochemistryresearchthemeshaveevolvedtothreebroad

areas,whichwedefineas:DynamicCellBiology,MembraneBiologyandEnzymology.TheyspansinglemoleculestudyofDNA-proteininteractionstoin vivomodelorganismstudiesofimmunecellsinteractingwithcancercells.Thisbroadresearchbasemakes

BiochemistryatBristolattractiveasaplacetocomeforundergraduatestudentsthroughtoyoungscientistswantingtosetuptheirownlabs.Italsoenablesimportantinterdisciplinaryinteractionsandcollaborationswith

chemists,physicistsandcliniciansbothwithintheUniversityandbeyond.Importantly,thismeansthatourundergraduatesareexposedtocutting-edgeresearchspanningthenanomolecularthroughtoclinical

translationalstudies,andhopefullygivingthemtheopportunity,notonlytobecomewell-trainedandroundedbiochemists,butalsotofindwhatinspiresthemmost.

BiochemistryinBristolreceivesstrongresultsyear-on-yearfromourundergraduatesintheNationalStudentSurvey.Ofcourse,weworkinanationallyandinternationallycompetitiveclimateanditisveryimportantthatwemaintainourpopularitywiththestudents.TeachinghasalwaysbeenveryimportanttotheSchool,andwillremainso,informedbyourwide-ranging,leading-edgeresearchactivities.Anotherofstrengthsisourtutorialsystemthat,despitepressuresontime,isexpandingandevolvingeachyearandincreasinglyfunctionstohonetheresearchandtransferableskillsofourstudents.MaintainingthisrelationshipbetweenstaffandstudentsandkeepingafamilyatmospheresuchthatstudentsfeelattheheartoftheSchoolwillbeakeychallengeforthecomingyearsasstudentnumbersexpandtoreflectthesuccessesandpopularityofthecourse.

Practicalworkinteachinglaboratoriesinthefirstandsecondyears,andindividualresearchprojectsinthe


The future of the Department

As demonstrated in this volume, 50 years of Biochemistry at Bristol has produced many research successes and has inspired generations of research

scientists, now scattered about the world, who were taught as undergraduates or trained as PhD students or postdocs here in Bristol.

Biochemistry in Bristol receives strong results year-on-year from our undergraduates in the National Student Survey

finalyear,areintegraltotheBristolBiochemistryBScexperience.Despitetheextrapressurethatincreasedstudentnumbershaveplacedonourresources,wefeelthisisaparticularstrengthofourcourses.Wearelookingatincreasingtheoptionsheretocaternotonlyforthosestudentswhoarelookingataresearchcareer,butalso

forthosewhoarelookingtoapplytheskillstheyhavelearntduringthecoursetoothercareerpaths.Thechallengeisalwaystomaintaintheseimportantsellingpointswhilstrecruitingthebestnationalandinternationalstudentsinanincreasinglycompetitiveenvironment.

OurPhDstudentnumbershaveexpandedrelativelyslowlyinrecentyears.Manyofourpostgraduatestudentsarenowrecruitedthroughourcollaborativedoctoraltrainingprogrammes.ThisisanareathatBiochemistry,inworkingwithotherschools,facultiesanduniversities,hashadseveralbigrecentsuccesses.Itis

importantthatwecontinuethistrend;maintainingPhDstudentnumbersiskeytokeepingourresearchactivitiesvibrant.

RecruitingtalentedstaffisoneofthemostimportantrolesofaHeadofSchooland,ofcourse,thecurrentfinancialclimatemeanstherearelikely

tobefewstandardopportunitiestodothis;weneedtothinkoutsidetheboxperhapstosolvethisone!Oneaimwillbetonurturethecareersoffutureresearchstarsbyattractingandsponsoringtheverybestjuniorresearchfellows.

IamdelightedtobetakingoverasBiochemistryHeadofSchoolinAugust2014,andIhopethenext50yearswillbeasexcitingforBristolBiochemistryasourlasthalfcentury.

Kate NobesHead of School of BiochemistrySummer 2014

One aim will be to nurture the careers of future research stars by attracting and sponsoring the very best junior research fellows

School of BiochemistryUniversity of BristolMedical SciencesUniversity WalkBristol BS8 1TD

Tel: +44 (0)117 33 12167

bristol.ac.uk/biochemistry

50 years of biochemistry - university of bristol · 50 years of biochemistry. b ristol biochemistry...

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