The Astbury Centre for Structural Molecular Biology ANNUAL REPORT 2016 Front cover illustration Folding of the protein Im7 in the presence or absence of the small, periplasmic ATP-independent chaperone Spy from E. coli. Im7 is shown as a multi-coloured protein that is helical in both the folding intermediate (I) and in the native folded state (N) and lacks any persistent secondary structure in the unfolded state (U). Spy is shown as a blue cradle-shaped homodimer. The kinetic mechanism of Im7 folding in the presence of Spy was investigated as part of a collaboration between the Radford (Leeds) and Bardwell (Michigan) groups and published in Nat. Struct. Mol. Biol. in 2016. More details can be found on p58 of this report. Acknowledgement The Astbury Centre for Structural Molecular Biology thanks its many sponsors for support of the work and its members for writing these reports. The report is edited by David Brockwell. This report is also available electronically at www.astbury.leeds.ac.uk I prefix Mission Statement TheAstbury Centre forStructural Molecular Biologywillpromoteinterdisciplinaryresearchofthe higheststandardonthe structure andfunctionofbiological molecules, biomolecularassemblies andcomplexes usingphysico-chemical,molecularbiological andcomputational approaches. www.astbury.leeds.ac.uk II prefix Introduction Welcometothe Annual Report of theAstbury Centre for2016. We have hadanother very busy andsuccessful year andthisletterhighlights afew of ourmanysuccesses.The Astbury Report is ashining exampleofthe buoyancy of ourscience, thestrengthofour community andour collaborations that go hand in hand with thecontributionsour members make to others through engagementinpublic-facingevents. Iwould liketothank every member of theCentre fortheir hard work over theyear: ourSupport staff, Technicians, Facility Managers, Students, Post-docs, Fellowsand Academic staff. And, of course,LucyGrayfor wonderful organisation andher excellent administrative support.Our successcomes fromour strong multidisciplinary science, as well as ourcollegialityand teamwork.Thank you all! During2016the Centre continued in its questof“UnderstandingLifeinMolecularDetail” through multipledifferentactivities, includingseminars, publications, public lectures andother events.Wecontinued to enjoyanexcellent seminarseries(organised by JoeCockburn), hosting10lectures during theyearwithspeakersfromthe UK andEurope.Awonderful tenth Annual AstburyLecture wasgiven by SirVenki Ramakrishnan,FRS,(MRC Laboratory of MolecularBiology)onthe 24th June, entitled “The use of recentadvances in electron microscopy to studyribosome structure".Thisannualevent wastraditionally followed by (a rainy!)sportsday andamuch enjoyed barbecue hosted by theAstbury Society (see http://www.astbury.leeds.ac.uk/about/society.php). 139members attended theCentre’s Biennial Away Day, held on September16th at TheThackrayMedical Museum where students,post-docs andPIs shared their recent excitingscientificdiscoveries, through talks, posters andthe ever-popular “Flash Poster”presentations. Aparticularhighlight of theyearwas launching thefirst ever AstburyConversationthatwas held on 11th &12thApril2016. More than 250eminent researchers from aroundthe world attendedthe AstburyConversation–thefirst internationalevent of itskindatthe University dedicated to thesubject of structuralmolecularbiology.The two-dayevent beganwithan academicresearchsymposium whichwas followedbyapublic exhibitionshowcasing the research andtechnologiesusedinthe University’s AstburyCentre forStructural Molecular Biology. Thefinal highlight wasalecture by NobelLaureate Professor Michael Levitt, FRS, during whichheexplained howcomputer modellinghas advanced ourknowledge of the molecularprocesses underpinninglife, health anddisease andwhatthe futureholds forthis area of science. Youcan watch hislectureagain on YouTube (https://www.youtube.com/watch?v=wtQY9IfBqPc)and see http://www.astburyconversation.leeds.ac.uk/ forphotosofthe Conversationevent itself. He also talked abouthow hiscareerdeveloped fromachildhood in SouthAfrica,through research in theUK, Israel andthe USA,tohis NobelPrize in 2013.The AstburyConversationwill run biennially andplans arenow underway forthe 2018 AstburyConversationthatwillbeheld on 16th &17th April 2018 –pleaseadd thesedates to your diary nowand we look forward to seeingyou there! TheCentrewelcomed Richard Bayliss, JuanFontana, Elton Zeqiraj, Glyn Hemsworthand MeganWrighttothe membershipin2016. As aresultofgenerousfundingfromLeeds alumnus, PeterCheney,wewelcomed visits fromProfessors Carol Hall (NorthCarolinaState University,USA),HerbertWaldman(MaxPlanck, Germany) andHarryTakagi(NIH, USA)and several events/activitieswere held to providethe opportunityfor Fellows andAstbury members to meet andplancollaborations.Wehavereceived fundingfor three more Cheney Fellows in 2017 andlookforward to welcomingKelly ChibaleUniversity of Cape Town,(South Africa),Steve Polyak (University of Washington,Seattle, USA) andPrebenMorth(University of Oslo,Norway) (see http://www.astbury.leeds.ac.uk/people/fellows.php). We were delighted to welcome many PhD students andpostdocstothe Centre this year,bringing ourtotal numbersto>300,including69academicstaff, 208PhD students,93postdoctoral researchers and9Research Fellows. III prefix AstburyCentre members publishedtheir research in awiderange of journals in 2016 anda full listcan be foundatthe endofthisreport. In termsofgrantincome,Astbury membersalso enjoyedmanysuccessesin2016. Togetherwith£9.3M of newprojectand programme grants, this brings theAstbury grantportfolio to astriking£52Mshare of £85M of grants: an impressive figure that is testamenttothe hard work andsuccess of ourmembers.Some of thelarger awards included a£1.25MEPSRC EstablishedCareer FellowshiptoAdamNelson;a£1.5M Cancer Research UK Programmegrant to Richard Baylissand Wellcome Trustinvestigator award (£1.8M)toSheenaRadford.LarsJeuken, Michael McPherson andDarren Tomlinson were part of asuccessfulUniversity of Leedsconsortiumbid (“Accelerating Developmentof InfectionDiagnostics forPatient Management andReductionofAntibioticMisuse”(£3.8M) fromthe MRC-coordinated AMR2 initiative. We are much indebted to thefunding agencies that support ourscience, includingBBSRC,EPSRC,MRC,the WellcomeTrust,charities, ERC, EU andIndustry. We also acknowledge, withthanks, thesupport of theUniversity of Leeds; theFaculties of Biological Sciences andMaths andPhysical Sciences andthe Schools of Chemistry,Molecularand CellularBiology,Biomedical Sciences andPhysicsand Astronomyfor theirsupport of theCentreand ourresearch. Therewas continued success in 2016 forseveralmembers of theAstbury Centre in termsof peer recognition. Alison Ashcroft wasawarded Life-Membershipofthe BritishMass SpectrometrySocietyand Andy Wilson wasannounced as the2016recipient of theRSC Norman Heatley Award forthe developmentofmethods to interrogate andmanipulate protein- proteininteractionsusing biomimetic approaches.Our students andpost-docs also were awardedmanyprizes fortheir contributionsatconferences andmeetings that spanthe globe: EthanMorgan(Wellcome Trustfunded)was awarded thirdplace in thenationalYoung Microbiologistofthe Year competition; Emma Pool (Zhougroup) wonthe best poster pricefor herposteratthe RSC Northern Dalton Meeting, PatrickKnight(BBSRC DTPstudent)won a poster prizeatthe 2016 BMSS meeting, Sarah Hewitt(Wilson group)was awarded aposter prizeatthe MSMLGmeeting in Bath forher work on rutheniumbased protein surface mimetics.Welldoneall. TheAstbury Society,led by thepresident Matt JacksonplayedaspectacularroleinAstbury activities in 2016.Eventsincludedthe famous Christmasquiznight,and ahugelysuccessful fourth MayBall. With continuedfundraisingthrough cake bakesand coffee mornings, the Society continuestosupport the“LeedsChildren’sCharity”withdonations reaching an impressive £2884.15 to date. Ihopethatyou enjoyreading this Annual Reportand its newlook. Thankyou to David Brockwelland Lucy Gray forediting this report,everyonewho contributedtoit, andall who participated in theAstbury Centre’s activities in 2016. Ilookforward to continuingour successes in theyearahead. Sheena E. Radford,FMedSci,FRS Director, AstburyCentrefor Structural MolecularBiology, Leeds, March 2016 Please notethatthisreport(as well as thosefromprevious years) is also availableasaPDF document whichcan be downloaded from ourwebsite (www.astbury.leeds.ac.uk). www.astbury.leeds.ac.uk IV prefix CONTENTS Pages Efficiency of energy trapping by Light-Harvestingproteins 1 Peter Adams Biomolecularmassspectrometry andstructuralproteomics 2-3 JamesAult, SamuelBunce,Antonio Calabrese, Owen Cornwell, Paul Devine, Rachel George,Kate Groves, PatrickKnight, Esther Martin, TomWatkinson, Leon Willis,Lydia Youngand Alison Ashcroft Host-cellinteractions of RiskGroup4viruses 4-5 Rebecca Surtees, Amelia Shaw,Jamel Mankouri,ThomasEdwards and JohnBarr Themany(interacting)faces of Aurora-A kinase 6-7 Selena Burgess, Mark Richardsand Richard Bayliss Bio-inspired model membranes and light-harvestingnanomaterials 8-9 Sanobar Khan,MengqiuLi, StephenMuench, Lars Jeuken andPaul Beales Proteinengineeringofaldolases 10-11 ClaireWindle,RobertSmith,AlexMoloney, Naim Stiti, Adam Nelson andAlanBerry Engineeringnovel naturalproductsand bindingmotifs 12-13 Ieva Drulyte, EmilyTurri,AdamNelson andAlanBerry Economicaland scalable synthesis of 6-amino-2-cyanobenzothiazole 14 JacobHauser, Hester Beard, Stuart Warriner andRobinBon Structuralstudiesofauto-inhibitionand mutationalactivationinfibroblast 15 growth-factorreceptors