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Institute for Life Sciences News and features: Researching biofilms in infant feeding tubes Spotlight on: Pioneering research enabled by disruptive technologies Publications: A sample of research outputs from our PhD students July 2019 ADVANCING LIFE SCIENCES ADVANCING LIFE SCIENCES

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Institute for Life Sciences

News and features: Researching biofilms in infant feeding tubes

Spotlight on: Pioneering research enabled by disruptive technologies

Publications: A sample of research outputs from our PhD students

July 2019

ADVANCING LIFE SCIENCES

ADVANCING LIFE SCIENCES

Find out more: www.southampton.ac.uk/ifls

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WELCOME CONTENTS

LifeSciencesareessentialtoourwellbeing,theeconomyandtheprotectionofanenvironmentcriticaltooursurvival.TheLifeSciencescommunityattheUniversityofSouthamptonisattheforefrontofapproachestoaddresstheseglobalchallenges,breakingthetraditionalmouldofsolvingproblemswithintheconfinesofadiscipline.

Wehaveanestablishedreputationforworkingcollaboratively,bytakingdisruptiveapproachesandriskthroughinterdisciplinaryteamscience.Withinterdisciplinarycultureattheheartofourcommunity,wefocusonfourareasofexcellence:HealthandMedicine,andLivingSystems,alongsideDisruptiveLifeTechnologiesandInsightsthroughData.Thelatterprovidetheadvancedtoolstodriveourunderstandingatthefrontiers.

Inpreviousreports,wehavefocusedontheexpansionofourimpactinregionalactivitiesandhowwehavecontributedtogovernmentstrategy.Inthisreport,wecontinuetohighlightourimpactthroughourengagementwithTheRosalindFranklinInstituteandTheAlanTuringInstitute,aswellasshowcasingourcurrentcollaborations,technologicalbreakthroughsanddemonstratingtheincreasingimportanceofdatainallofourresearch.

YoucanalsoseeaselectionofrecentpublicationsfromourcohortofinterdisciplinaryPhDstudentsastheydevelopintoindependentresearchersandfutureleaders.

Professor Peter JS Smith DirectoroftheInstituteforLifeSciences

TheLifeSciencesareakeycomponentoftheUKstrategyforgrowth,underpinningourengagementwithhealthandthebioscienceshereattheUniversityofSouthampton.

Thisyear’sreportfromtheInstituteforLifeSciences(IfLS)highlightsthecentralroleitcontinuestoplayintermsofourinstitutionalaspirationsandachievements,asadynamic,consistentandcollaborativechampionofourlifesciencesportfolio.

Professor Mark SpearingPresidentandVice-Chancellor(Interim)UniversityofSouthampton

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FEATURE: Cross-Institute Engagement Pioneeringresearchenabledbydisruptivetechnologies

12Living SystemsCatalysingourexpertiseinecologyandevolution

18PublicationsAsampleofpublicationsfromourinterdisciplinarypostgraduatestudents

08 Health and Medicine Collaboratingattheforefrontof

cancerimmunology

Front cover image: First-of-a-kind soft tissue-optimised micro-computed tomography (μCT) scanner in Southampton for 3D X-ray histology.

10Life TechnologiesRevolutionisingbiomedicalimaging

14Insights through DataTransformingprecisionmedicinethroughdataanalytics

16 News in BriefAround-upofnewsfromacrosstheInstituteforLifeSciences

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Southampton is renowned both nationally and internationally for the strength and breadth of its interdisciplinary life sciences research, and is particularly proud of its revolutionary collaboration between medical, health and natural sciences.

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PIONEERING RESEARCH ENABLED BY DISRUPTIVE TECHNOLOGIES

Fromidentifyingindicatorstopredictacceleratedageing,tousingmathematicalmodellingtounderstandbreastcancer,andfromdevelopinghighresolutionmicroscopytoolstousingchemistryprocessestocreatenewantibiotics,Southampton’slifesciencesportfoliospansmanyareasacrosstheUniversity.

TheglobalrecognitionoftheUniversityasahubofexpertiseinthelifescienceshasledtotheorganisationbecomingapartneroftwoleadingUKinstitutionsthatarepioneeringresearch–TheRosalindFranklinInstituteandTheAlanTuringInstitute.

Southampton’s involvementTheUniversity’sInstituteforLifeSciencesDirectorandBoardMemberofTheRosalindFranklinInstitute,ProfessorPeterJSSmith,stronglywelcomesSouthampton’sinvolvementinthesetwoinnovativeinstitutions.

Hesaid:“Itisagreatpleasuretobecomeacorepartofthesetwomajorinstitutes.Itreflectsthestrengthwehaveinlifesciencesresearchacrossmanydisciplines.

“AtSouthampton,wearecapableofcontributingtoanumberofthecorethemesofTheRosalindFranklinInstitute,particularlywithourresearchindisruptiveadvancesinimagingtechnologiesfromthelargescaledowntotheatomicscale.

“WewillfeedintoprojectsthatTheRosalindFranklinInstituteisundertakingandwillbeattheforefrontofcutting-edgetechnologydevelopmentthatwillhelpdriveourownresearchforward.”

The Rosalind Franklin InstituteTheRosalindFranklinInstituteisdedicatedtotransforminglifesciencethroughinterdisciplinaryresearchandtechnologydevelopment.Itaimstoproducetechnologiesthatwillallowustoseethebiologicalworldinnewways,fromsinglemoleculestoentiresystems,speedingupdrugdesignanddevelopment,andpushingforwardourunderstandingofhumanhealthanddisease.

TheUniversityofSouthamptonisoneoftenuniversitiesatthecoreofTheRosalindFranklinInstitute,whowillworkwithindustrialandacademicpartnerstofosterinterdisciplinaryresearch,atscale,withrealimpact.

The Alan Turing InstituteTheAlanTuringInstituteistheUK’snationalinstitutefordatascienceandartificialintelligence.Itsgoalsaretoundertakeworld-leadingresearchintheseareas,applythisresearchtorealworldproblems,driveeconomicimpactandsocietalgood,leadthetrainingofanewgenerationofscientists,andshapethepublicconversationarounddata.SeveralmembersoftheIfLSarenowTuringFellowswithaccesstoopportunitiesandthewidernetwork.

Image: Extreme ultraviolet light generated by femtosecond lasers is used by Professor Jeremy Frey and Dr Bill Brocklesby for nanoscale imaging of neurons.

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Cross-Institute Engagement

Cross-Institute Engagement

Here we look at how some of our researchers are taking disruptive approaches to solve life science questions.

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Tackling antibiotic resistanceResearchbyProfessorSymaKhalidandherteaminChemistrywillhaveabigimpactonthecurrent,globalfightagainstantimicrobialresistance.

SymawillbeusingSouthampton’shighperformancecomputer–Iridis5–aswellasthenationalSupercomputer–ARCHER–tohelpdesignnewantibotics.

Theteamiscreatingaccuratecomputermodelsofmolecularassemblieswithinbiologicalsystemstobetterunderstandhowbacteriarespondtoantibiotics,inordertodevelopimproved,morepotentdrugs.

Shesaid:“WorkingwithTheRosalindFranklinInstitutewillfacilitatecross-disciplinarystudies,sowecancombineourcomputationalworkwithdatafromcolleagueswhodowet-laboratorysciencetoprovidegreaterinsights.”

Lens-less imaging at the nanoscaleAcollaborationbetweenChemistryandSouthampton’sZeplerInstitutehopestobringaninnovativemicroscopytoolapplicationthathasthepotentialtolookatbiologicalsystemsatamuchhigherresolutionanddefinition.

ProfessorJeremyFrey,fromChemistry,andDrBillBrocklesby,fromtheZeplerInstitute,areamongthefirstresearchersintheworldtodemonstratelens-lessimagingonactualbiologicalsamplesusingextremeultravioletlight,whichgivesmuchhigherresolutionthanopticalmicroscopy.

Jeremysaid:“Usuallymetalcoatingsorfluorescentdyesneedtobeaddedtosamplesbeforeimagesaretaken,butwehavebeendevelopingacoherentlightsourceoverthepastfewyearsthatenablesustotakemeasurementsfromsampleswithouthavingtodotoomuchtothesamplebeforehand.

“Thisisopeningupawholenewwayoflookingatthesub-cellularstructure,revealinginformationthathasn’tbeenseenatthislevelbefore.BytakingthisnoveltechnologytoTheRosalindFranklinInstitute,wewillhaveaccesstomuchlargerequipmentthatwillenableustoimprovetheresolutionofourlens-lessimagingtothenanoscale.”

Billadded:“Wearehopingthattheimagesthatwecannowproduceofnanoscalebiologicalstructurescanmakeacaseforinvestmentinthenextgenerationofthesetools.Wewillbecreatingapathwaythatcouldmakethisimagingequipmentmorecompactallowingittoberolledoutforusemoregenerallyinbiology.”

Theseadvanceswillcontributetothegeneralthemesofcorrelativemicroscopy–afocusofdevelopmentatTheRosalindFranklinInstitute.

Using mathematical modelling in predicting breast cancerDrPhilipGreulichisoneoftheUniversity’sfirstTuringFellowsandisinvestigatinghowstemcellsdivideanddifferentiate,whichiscrucialforunderstandinghowcancerdevelops.

CollaboratingwithDrSalahElias,alsofromtheIfLS,PhilipisusingmathematicalmodellingtestedonSalah’sexperimentaldata,toexplorewhetherthedirectioninwhichbreasttissuecellsdivide,candeterminethecellfateandwhattypeofcellitwillbecome.

Hesaid:“Ithasbeenshownthattheorientationofbreastcancercelldivisionismuchmorerandomthanthatofhealthycells.Wewanttofindoutifthiscouldbeapredictortocausecancerorifithasnorelation.BeingaTuringFellowIwillbeabletosharemyexpertiseinmathematicalmodelling,andIwillhaveaccesstoresearcherswhoworkwithlargehigh-dimensionaldatasetswhocanhelpmeanalysethecomplexdatainvolvedinmyresearch.”

Predicting the ageing processTuringFellowandIfLSmemberDrNickFuggle,fromtheMRCLifecourseEpidemiologyUnit,islookingatindicatorsthatcanpredictthoseatriskofacceleratedbiologicalageingwithafocusonmusculoskeletalhealth.

Byusingclinicalparameters,epigeneticmarksandspecialistimaging,heistryingtoidentifywhomaybeatriskofconditionssuchasosteoporosis,osteoarthritisandsarcopenia(muscleloss).Thiswouldallowearlyinterventionandameliorationoftheriskofthesediseasesofmusculoskeletalageing.

Hesaid:“TheTuringFellowshiphasallowedmetobuildrelationshipsandcollaborationsacrossTheAlanTuringInstitute.Ihaveconnectedwithcolleagueswhohavediverse,interdisciplinaryinterestsinmachinelearning,healthservices,epigeneticsandimageprocessing,whichisresultinginasubstantialbroadeningofmyresearchhorizons.”

“Itisagreatpleasuretobecomeacorepartofthesetwomajorinstitutes.Itreflectsthestrengthwehaveinlifesciencesresearchacrossmanydisciplines.”

Professor Peter JS Smith Director of the Institute for Life Sciences

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For more than 40 years, scientists at the University of Southampton have been at the very forefront of cancer immunology research and have an international reputation for bench to bedside results.

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programmeinapplicationsoftopologyspecificallytocancerimmunology.”

Studying at the boundaries of Maths and MedicineIfLSstudentJosephEganisamathematicalmodellerbasedattheCCI,whoisusinghismathematicalskillstohelpthecancerimmunologistsbetterunderstandtheinteractionsbetweencellsoftheimmunesystemandtumourcells.

HewasinspiredbytheinterdisciplinaryresearchattheCCIanddecidedtotakeupthePhD,whichcrossestheboundariesofMathsandMedicine.

Hesaid:“I’mreallyinterestedinusingmymathematicalmodellingskillsinareal-worldsetting.Iworkwithateamofleadingimmunologists,andtheideaofbeingabletodevelopmodelsbasedontheirexperiments,andforthesemodelstothenguidefutureexperiments,isincrediblyexciting.”

Attracting leading international researchersSouthampton’sinterdisciplinarycultureandinternationalreputationfortranslational

researchwereinstrumentalinattractingProfessorSallyWardandProfessorRaimundObertotheCCI.

Leadersinthefieldofantibody-relatedtherapeutics,thepairrelocatedtotheCCItoheadupajointinterdisciplinarylaboratory.ThislaboratorycombinesSally’sexpertiseinfindingnewwaystoengineerantibodiestohelpthemdestroycancercellsandunderstandhowimmuneresponsescanbemodulatedfortherapy,andRaimund’sresearchindevelopingnewsuper-resolutionimagingtechniquestostudythefateoftherapeuticanti-cancerantibodiesastheyattackcancercells.

Theirpre-clinicalresearchhasalreadyhelpedthemsecuretwokeygrantstosupporttheirresearch–£2.2mfromCancerResearchUKand£2.7mfromtheWellcomeTrust.

Sallysaid:“WewereimpressedwiththestrongethosofinterdisciplinarityatSouthampton.TheCCIandtheIfLSaregreatexamplesofhowthiscanbeembeddedwithinorganisations.WehavealreadybeenliaisingwithmembersoftheIfLSaboutpotentialwaysofworkingtogetherinthefuture.”

Findoutmore: www.southampton.ac.uk/youreit

TheCentreforCancerImmunology(CCI)–theUK’sfirstdedicatedcentreforcancerimmunologyresearch-wasdevelopedbytheUniversitytobringtogetherworld-leadingscientiststoimproveourunderstandingofhowimmunitytotumourscanbestimulatedandtoexpandclinicaltrialsanddevelopmorelifesavingdrugsinthisexcitingandpromisingareaofcancerresearch.

AttheheartoftheCCIistheethosofinterdisciplinarityandtranslationalmedicine–principlesthataresupportedbytheUniversity’sInstituteforLifeSciences(IfLS)withwhichtheCCIhasacloseaffiliation.

CCIDirectorandDeputyDirectoroftheIfLSProfessorTimElliottsaid:“ThesetwoprinciplesarepillarsoftheIfLSandIwaskeentoensurethattheyarecentraltotheresearchstrategyoftheCCI.Ourresearchincancerimmunologyreliesonscientistsfrommanydifferentfields

workingcloselytogethertosolvekeychallengesanddriveforwardresearchinthisarea;anditsapplicationtotreatingcancerreliesonintegratedteamsofdoctors,scientists,nursesandclinicaltrialsexperts.”

A close collaborationTimsaid:“TheIfLShascreatedanenvironmentwhereresearchersunderstandthevalueofworkingacrossdisciplines.Thishashelpedusestablishrealinterdisciplinaryconnectionsthatareenablingustochannelourdiscoveriesfromourlabstopatientsfortheveryfirsttime.

“TheIfLShashelpedtobrokerimportantinterdisciplinaryconnectionsforus.Combiningourimmunologyexpertisewithworld-leadingengineers,computerscientists,chemistsandmathematicians,allowsustotacklebigquestionslikehowthehumanimmunesystemreactstocancer,ininnovativeways.”

Embedding in the CCIIfLSmemberandProfessorofPureMathematicsJacekBrodzkiisthefirstresearchsabbaticalfellowtospendayearembeddedintheCCI,usinghisskillsintopologicalmodellingtechniquestobetterinformandunderstandbigdatainscientificexperiments.

Jaceksaid:“Cancerimmunologyresearchisbasedoncutting-edgeexperimentsthatcreatevastamountsofreallycomplexandmultidimensionaldatawhichisnoteasytoanalyseusingthestandardmethods.Topologicaldataanalysisprovidesnewinsightsintotheoutcomesofexperimentsandsuggestsnewwaystoorganiseandinterpretthedata.

“Mysabbaticaloffersmethecrucialopportunitytospeakdirectlytotheexpertstounderstandtheunderlyingproblemsandmotivationsfortheexperiments.IamplanningtodevelopnewmethodologiestosupporttheworkattheCentre,andsetupanewresearch

COLLABORATING AT THE FOREFRONT OF CANCER IMMUNOLOGY

“TheCentreforCancerImmunologyisuniqueinitsinterdisciplinaryandtranslationalapproachtocancerresearchinvolvingresearchersfrommanydifferentdisciplinesrangingfrommathematicianstoclinicalresearchers.CollaboratingwithIfLSresearchersprovidesexceptionalopportunitiesforgroundbreakingresearch.”

Professor Raimund Ober Professor of Imaging and Biomedical Engineering, Centre for Cancer Immunology, Southampton

Professor Tim Elliott Professor Sally Ward

Professor Jacek Brodzki and Joseph Egan

The Centre for Cancer Immunology

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Health and Medicine

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REVOLUTIONISING BIOMEDICAL IMAGING

“Thisresearchisanexcellentexampleofhowfundingofasmallpilotprojectlaysthefoundationresultingseveralyearslaterinmajorgrantfunding.Thisisafantasticcollaborativeachievement.”

Professor Peter JS Smith Director of the IfLS

“CouplingexpertisefromMedicineandEngineeringacrossthedisciplinaryboundarieshasbeenfundamentaltothisprojectandhasresultedinsignificantresearchfundingandcommercialengagement.”

Professor John Holloway Associate Dean (Research) in Medicine

“Thisprojectbuildsonourlong-standingcollaborativecommitmenttohigh-resolutionX-rayimagingatSouthampton.Inthefieldofimagingconventionallymountedbiomedicalsamples,theteamsatSouthamptonareclearlyworldleaders.”

Ian Haig VP Engineering, X-ray Special Projects Nikon X-Tek Systems Ltd

Over the last two decades, high-resolution 3D imaging of hard tissues such as bones and teeth by X-ray micro-computed tomography (µCT) has become a routine tool in biomedical and pre-clinical research.

Untilrecentlyithasbeenthoughtimpossibletogeneratesimilarhigh-resolutionµCTimagesfromsofttissuesthathavenotbeenspeciallypreparedforincreasedX-raycontrast.

PioneeringresearchbyaninterdisciplinaryteamofInstituteforLifeSciences(IfLS)membershasrevolutionisedthisareaofbiomedicalimagingbydevelopingaµCTscannercapableofproducingnon-invasive3Dscansofsofttissuebiopsiesatmicroscopicresolutions.ItrevealsfeatureshundredsoftimesmoredetailedthanconventionalCTscans-comparableto2Dlightmicroscopyimagesfromconventionaltissuesections.

ThefirstgenerationofthisscannerhasbeenoperationalinSouthamptonforthelastthreeyearsandavarietyofsofttissuesamplesincludinglung,colonandliverhavebeenimagedandanalysed.TheworkisattractinginternationalinterestfrombiomedicalresearchersandclinicianskeentotryµCTintheirwork.

Theresearchhasfurtherstrengthenedandestablishednewrelationshipswithindustrialpartners,includingNikonX-TekSystemsLtdandDECTRISLtd.TheteamatSouthamptonhasreceivednearly£2mofWellcomeTrustfundingandsupportfromindustrytodevelop,standardiseanddriveuptakeoftheirinnovativeμCTtechnologyfor3DX-rayhistology.

The historyFiveyearsago,thehighlyinterdisciplinaryteamofresearchersfromMedicineandEngineering,togetherwiththeBiomedicalImagingUnit(BIU)andtheµ-VISX-rayImagingCentre,receivedproof-of-conceptfundingfromtheIfLS.

DrPhilippSchneider,AcademicDirectoroftheµ-VISX-rayImagingCentre,said:“ThatinitialIfLSfundingencouragedustocomeclosertogetherasacohesiveunit,tofurtherdevelopourresearch,andgeneratemicroscopic3D

imagesoflungtissuefromwhichwecouldgatherproof-of-principledatatodemonstratewhatweweretryingtoachieve.”

DrPeterLackie,AcademicLeadintheBIU,said:“Thepilotdatawecreatedwascrucialandground-breaking.Itwasthefirsttimethatanyonehaddonethis3Dscanningofsofttissueinstandardwaxblocks,anditallowedustobidforfurtherfundingculminatinginthelargeWellcomeTrustgrants.”

Potential impactThishigh-resolutionwayofscanningsofttissuesistheimagingofthefuture.Itopensupawealthofnewinformationtobiologists,biomedicalscientists,medicalresearchersandclinicians,enablingthemtoseeandquantitativelyanalysethemicrostructuresofsofttissuebiopsiesintheir3Dcontext.

Theselungtissuescanshavealreadyhelpedmedicalresearcherstounderstandmoreaboutrespiratorydiseases.Theyhaverevealedimportantdetailsoftheprocessesinvolvedinlungfibrosisandchronicobstructivepulmonarydiseasethatwillhelpinformfuturetreatments.

ManageroftheBIUDrAntonPagesaid:“Theresearchisacriticalpartofourinternationallycompetitive3DbiomedicalimagingcapabilityatSouthampton.”ProfessorIanSinclair,SeniorAdvisoroftheµ-VISX-rayImagingCentre,said:“Wehavealreadyhadinterestfrommedicaland

biomedicalresearchers,andcliniciansacrossEuropewhowouldliketoemploythistechnology.”

CollaborationTheteam’smaincollaboratorduringtheprojecthasbeenNikonX-TekSystems,whoco-fundedtwoPhDstudents,anddevelopedthescannerthatwasusedfortheinitialworkfundedbyaWellcomeTrustPathfindergrant.

InadditiontothesystematSouthampton,otheridenticalprototypeshavebeeninstalledatGreatOrmondStreetHospital(GOSH)LondonandMemorialSloanKetteringCancerCentreinNewYorkandarebeingusedtodevelopotherapplicationsofµCTinmedicine.

Theteamhasalsoliaisedwithexperthistopathologistsaroundtheworld,receivingpositivefeedbackaboutthe3Dmicrostructuresandthediagnosticallyrelevantinformationtheirscansreveal.

The futureTheirsecondWellcomeTrustgrantaimstoincreasethescanner’sthroughput;standardisetheimageacquisitionandprocessingworkflows;raiseawarenessanddriveuptakeof3DX-rayhistology;andfurtherbenchmarkstate-of-the-artX-raysourceanddetectortechnologytobeintegratedinthefuture.TheyarelookingforwardtocollaboratingwithUniversitycolleaguestofullyexploittheirnoveldata,usingmachinelearningtoolsandartificialintelligencefordiagnosisofdiseasesandpatientstratification.

DECTRISLtdistheworldleadingHybridPhotonCounting(HPC)detectormanufacturerforscientificapplicationsandwillprovideaHPCdetectortogeneratezeroelectronicnoiseandfastimagingathighresolutionandmaximumsharpness.

Findoutmore: www.xrayhistology.org

3D X-ray histology: Setting up a μCT scan of a standard human biopsy specimen.

Image: First-of-a-kind soft tissue-optimised micro-computed tomography(µCT) scanner in Southampton for 3D X-ray histology. https://doi.org/10.1016/j.ajpath.2019.05.004

Life Technologies

CATALYSING OUR EXPERTISE IN ECOLOGY AND EVOLUTION

Withspeciesunderthreatandhabitatsbeingdestroyed,wearehavingtotakeacloselookathowwecanprotectourecosystemsandsustainourlivingsystemsforthefuture.

AtSouthampton,wehavesignificantresearchstrengthsinecologyandevolutionthatarehavinganimpactonunderstandingtheresilienceofspeciesfromthesmallestorganismtothemostcomplexecosystem.

ThisexpertiseacrosstheUniversityisbeingdrawntogetherbytheInstituteforLifeSciences(IfLS)tocreateastrong,cohesivenetworkofresearchandeducation–theEvolutionGroupthatisfacilitatinginterdisciplinaryworkbetweendiverseareasincludingOceanandEarthSciences(OES),BiologicalSciences,Mathematics,ElectronicsandComputerScienceandEngineering.

Southampton’s expertiseDirectoroftheIfLSProfessorPeterJSSmithsaid:“AcrosstheUniversitytherearetremendousskillsetsintheareasofecologyandevolutionandweareseizingtheopportunitytobringthisgrouptogetherasonecohesivecommunity.

“AspartofSouthampton’slifesciencesstrategy,wewanttheUniversitytoberecognisedasahubofexpertiseintheseareas.Bydrawingtogetherallofthesegroups,theywillbeinastronger,unifiedpositiontoexpandtheirresearchimpact,enablemorecollaborativeopportunities,andfurtherincreasetheirsignificantgrantincome.”

Workingtogethertotargeteco-evolutionarysynergies,IfLSmemberDrThomasEzardisco-ordinatingtheevolutionaryaspectswithDrJasminGodboldco-ordinatingontheecologyside.

Thomassaid:“TheUniversityisdemonstratingtheimpactoftheexcellentresearchthatisbeingcarriedoutinvariousareasofevolution.Inthelastthreeyears,wehavewonmorethan£2.5mfromtheNaturalEnvironmentResearchCouncil(NERC)andtheBiotechnologyandBiologicalSciencesResearchCouncil(BBSRC).Wearealsoakeypartofaninternationalmultidisciplinaryteamtakingpartina$8.5mprojectsupportedbytheJohnTempletonFoundationwhichrecognisestheimportanceofintegratedsciencesacrossdisciplines.”

Studying the adaptive response of batsIfLSmemberDrOrlyRazgourisaNERCIndependentResearchFellowandLecturerinEcologywhoisexploringtheevolutionaryandecologicalresponsestoglobalchangetounderstandhowwecanbettermanagetheenvironmentandconservebiodiversity.

Sheprimarilyfocusesonlookingattheeffectofenvironmentalchangeonbatsandthewaytheyhaverespondedtothesechanges.

Shesaid:“Batsaregoodindicatorsbecausetheyareawidespread,diversegroupoforganismsthatenableustostudythepotentialresponsesofbothbirdsandmammals.MyresearchisinvestigatinghowenvironmentalchangehasaffectedbatspeciesacrossEurope,AfricaandtheMiddleEasttohelpidentifythetraitsthatmakethemparticularlyvulnerabletofuturechange.

“Byunderstandinghowtheyadaptandhowtheabilitytoadaptdiffersbetweenpopulations,wecanlookatwhereweneedtofocusourconservationefforts.”

Orlyrecognisestheimportanceofinterdisciplinaryworkinherresearch.Shesaid:“Thesearebigglobalissuesthatrequireanalysisanddatafromdifferentdisciplinesinordertofullyunderstandtheproblemsandwhattheresponsestothoseproblemsare.

“IamworkingwithotherevolutionarybiologistsfromacrosstheUniversitytotryanddevelopmathematicalmodelsofevolutionandadaptiveresponses.Thesedifferentstrengthsfromdifferentfacultiesarevitaltoadvancemyresearch.”

Crop domestication as a model for evolutionAssociateProfessorinBiologyDrMarkChapmanisusingBrassicacropstodeliveranewunderstandingofhowevolutionworks.

AspartofhisNERCandBBSRCprojectwithDrThomasEzard,fromOES,MarkisexaminingBrassicas,suchasturnipsandcabbages,tofindouthowpopulationsdivergeandbecomeseparatespecies.Heislookingathowindividualplantschangetobestmatchtheprevailingenvironment–knownasphenotypicplasticity.

Hesaid:“Wehaveseenthatwildturnipsgrowninacultivated-likeenvironmentstarttoresemblecultivatedturnips,andtheirgeneexpressionstartstoaltertoo.Soweareaskingourselvesifwildspecieshavebeenselectedbyhumansbecauseofthisplasticity?

“ByanalysingseveralBrassicacropsandtheirwildrelatives,wecanseeifthesamechangeshappenindifferentspecies,givingusanewunderstandingofevolutionandhowimportantthedifferenttypesofplasticityareindrivingevolutionarydivergenceamongspecies.”

Safeguarding the future of our planet is the biggest challenge facing society today.

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01 DrJasminGodboldandDrAdamReedmeasuringthesizeofamudstarattheUniversity’sBiodiversityEcosystemFuturesFacility.

02 DrOrlyRazgoursamplingbatsinSpaintostudyadaptationsalongclimaticgradients.

03 DrMarkChapmanandpostdoctoralresearchfellowJasmineSabanprepareDNAsamplesforgenomesequencing.

04 FossilisedplanktonbeingstudiedinDrThomasEzard’slab

05 Examiningthephenotypesofplantsindifferentgrowthenvironments.

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Living Systems

Southampton’s unique in-depth expertise in multi-omic technologies, combined with access to patient cohorts from world-leading collaborative clinical partners, is helping to transform precision medicine across the disease spectrum from cancer immunology to respiratory conditions.

Thenewly-establishedIntegrativeMolecularPhenotypingCentre(IMPC)isbringingtogether’omicexpertsfromacrosstheUniversitytousemulti-omicdata,incombinationwithclinicaldata,tobetterunderstanddiseaseandenablemorepersonalisedandeffectivehealthcaretreatmentanddiagnosis.

ThenewCentre,whichispartoftheInstituteforLifeScience(IfLS),willdriveforwardinterdisciplinaryresearchusingmolecularphenotypingtoexploreindividualvariabilityingenes,environmentandlifestyle.Thiswillallowdoctorsandresearcherstopredictmoreaccuratelywhichtreatmentandpreventionstrategiesforaparticulardiseasewillworkinwhichgroupsofpeople.

Southampton’s unique positionDrPaulSkipp,AssociateProfessorinProteomics,isleadingthedevelopmentoftheCentrethatdrawstogetherexpertisefromMedicine,BiologicalSciences,MathematicsandEngineering.Hesaid:“Southamptonisinauniquepositionbecausewehaveexpertsinnumerous’omictechnologiesanddatascienceandhaveexcellentcollaborationwithourclinicalpartnersbothintheUKandacrossEurope.

“Itisonlybyworkingtogetherthatwecanreallyunderstandthemechanismsbehinddiseases.Notonlyarewecarryingouttheinnovative

researchhere,butourestablishedclinicallinksmeanwecantranslatethatresearchintotheclinicandthroughtothepatient.

“Byusingmolecularsignaturesfrommulti-omicsdata-genomics,transcriptomics,proteomics,glycomicsandmetabolomics-incombinationwithclinicaldata,wecanenablebettertailoringofexistingtreatments,andpavethewayforthedevelopmentofnewtherapeuticsanddiagnosticsforimprovedpatientoutcome.

“However,thedatathatwearegeneratingfromthisresearchishuge.TheIMPCwillenableustodevelopcriticalnewapproachestointegrateandanalysethisdataandextracttheinformationweneedfromthesebigdatasets.

“ThecombinationofalltheworkwearedoingatSouthampton,particularlyintheareasofcancer,respiratoryandinfectiousdisease,ischangingthewaywelookatdiseaseandplacesusasleadersinprecisionmedicine.”

Research impactSouthamptonisalreadymakinganimpactinmolecularphenotypingandprecisionmedicine:

TopoMD - isagroupofscientistsandmathematiciansfromtheUniversitywhoseexcitingresearchispromisingtorevolutionisehealthcarebyallowinghighresolutioninvestigationofmolecularmechanismsunderlyingdisease,andthereforeenabling

developmentoftargetedtreatmentsforapplicationinpersonalisedmedicine.Theyareusingrevolutionarytopologicalalgorithmstoplottheshapeofapatient’sgeneexpressionandcompareittotheshapeofgeneexpressioncharacteristicofdiseasesforpreciseandaccuratediagnosis.

Asthma –usingclinicaland’omicsdatafromhundredsofadultsandchildrenwithsevereasthmaweareabletounderstandmoreaboutdifferenttypesofasthmatoensurebetterdiagnosisandtreatmentforeachpersonanduncovernewinformationandideasthatcouldleadtothecreationofeffectivenewtreatments.Theteamhasrecentlyidentifiednovelmolecularsub-typesofasthmathatareusedinclinicaltrialstobetterpredicttherapeuticefficacy.

Cancer -incollaborationwiththeSouthamptonCentreforCancerImmunology,theteamisusingmulti-omicsapproachestoidentifyhumanleukocyteantigen(HLA)class-Iandclass-IIpeptidespresentedtoT-cellsinanumberofcancerswhicharecrucialfordesigninginnovativepersonalisedtherapeuticsandvaccinesagainstcancerandotherdiseases.

Breast cancer – usingmolecularphenotypingdatacollectedfrom3,000patientsoverfiveyears,wearediscoveringnewbiomarkersforassessingtheriskofdevelopingsecondarybreastcancer,breastcancerrecurrenceandhowdietandlifestylefactorscouldinfluencetheoutcomeofthedisease.

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TRANSFORMING PRECISION MEDICINE THROUGH DATA ANALYTICS

Image: Dr Paul Skipp15

Insights Through Data

ThreeyearsagoChriswonanationalaward-theprizeforbestresearchposterattheNationalNursesNutritionGroupannualconference.

Morerecently,hehasdevelopedarepresentativefeedingmodeltohelpsimulatebiofilmcontaminationoninfantfeedingdeviceswithinalaboratorysetting;istalkingabouthisworkatTheAmericanSocietyforMicrobiology’s(ASM)Annualconference,inSanFrancisco,forwhichhehasbeenawardedtheirASMStudentandPostdoctoralTravelAward;andisrunningaclinicaltrialatSouthampton’sPrincessAnneHospitalneonatalunit,collectingusedtubestogaina

deeperunderstandingonthetruediversityofcontaminants.

Hesaid:“Thedatafromtheclinicaltrialisbeinganalysedandisstartingtouncoverfascinatinginformationaboutthetruediversityofmicro-organismsfound,andhowdifferentspecificcareregimesarealteringthesepopulations.

“Therepresentativefeedingmodelaimstogetadeeperunderstandingofcontamination,butalsoprovideatoolforhealthcareprofessionalstomodelandunderstandhowdifferentfeedingandcareregimescouldhaveimpactsoncontamination.”

Chris’postgraduatethesisresearch,fundedbytheIfLS,HealthSciencesandBiologicalSciences,isnearingcompletion.Hesaid:“TheopportunitytoundertakesuchaprojectisonlypossibleduetothesupportandinfrastructureprovidedtomeaspartofmystudentshipandisarealtestimonytothequalityofresearchthatcanbeconductedattheUniversity.

“TheexperienceIhavegained,combinedwiththeopportunitiesaffordedme,hasallowedmetoenjoymyresearchexperience,andIamexcitedtocontinuemyresearchcareerintothefuture.”ChrisissupervisedbyDrSandraWilks,ProfessorBillKeevilandProfessorMandyFader.

InterdisciplinaryresearchersintheInstituteforLifeScience(IfLS)havereceivedthreeprojectgrantsfromtheGlobalChallengesResearchFund(GCRF)-a£1.5billionfundannouncedbytheUKGovernmenttosupportcutting-edgeresearchthataddressesthechallengesfacedbydevelopingcountries.

The IfLS-related projects are:

− AcademicsfromEngineeringandPhysicalSciences,HealthSciencesandMedicineareworkingonathree-yearprojecttoimproveaccesstoartificiallimbsinlowerandmiddleincomecountries.TwostudiesarebeingcarriedoutwithclinicianandeducationpartnersinCambodia,aimingtodevelopdigitaltoolstoincreaseprostheticandorthoticservices,trainprosthetist-orthotistsandensurefundingisspentmoreefficiently.

− Infectionresearchers,engineersandbioinformaticiansfromSouthamptonandUniversityCollegeLondonhavedevelopedanew3Dsystemtostudyhumaninfectioninthelaboratory.ThespheresareallowingresearcherstocarryoutaprojectinDurban,SouthAfrica,tofurtherinvestigatewhathappensinthehumanbodywhentuburculosisdevelops.Theirlong-termaimistoidentifynewantibiotictreatmentsandvaccines.

− ResearchersinSouthamptonandMalaysiaarecarryingoutapioneeringstudythatcouldleadtothedevelopmentofavaccinetopreventheadandneckcancer.TeamsbasedattheNIHRCRUKSouthamptonExperimentalCancerMedicineCentreandCancerResearchMalaysia,arestudyingprecancerouslesionsinthemouthwhich,ifleftuntreated,canprogressintoheadandneckcancer.Theyarefocusingontestingthelesionsformarkerswhichcanthenbetargetedbyvaccinationandisthefirststudyaimedatcreatingavaccinetopreventaformofcancerdeveloping.

InstituteforLifeSciences(IfLS)memberProfessorRoxanaCarare,togetherwithDrChristopherKippsattheUniversityHospitalSouthamptonNHSFoundationTrust,areleadingthecreationofanewinterdisciplinaryresearchcentretoaddressnationalchallengesinthefieldsofdementiaandbrainageing.

Theunderstandingofdementiaandneurodegenerativedisease,togetherwithimprovedtherapiesanddeliveryofcareforpeoplewiththeseconditions,isapressingneedintheUK,andtheSouthCoastregionisrecognisedasanareawheretheseproblemsareparticularlyacute.

TheInterdisciplinaryDementiaandAgeingCentre(IDeAC)isbringingtogetherlocalexpertisefromacrosstheresearchspectrumtoformadedicatedinterdisciplinarydementiaandageingresearchcentretoaddresstheproblemsinthiscomplexfield.

TheIDeACnetwork,whichisworkingcloselywiththeIfLS,includesbasicscientists,clinicians,healthandsocialcaredeliveryresearchers,epidemiologists,imagers,mathematicians,andcomputinganddatascientists.

Roxanaisinternationallyrenownedforherresearchintothecausesofdementiaandfindingnewtherapeutictargetstohelpthemanypeopleaffectedbythedisease.Shesaid:“Thereisconsiderablelocalexpertiseinageinganddementiaandouraimistobringthistogetherintoanetwork.IDeACwillseektoenergise,co-ordinateandfocuseffortstoputusinastrongpositiontoattractandsustainfundingforanationallyrecognisedcentre.”

Christopherisabehaviouralneurologistwithexpertiseindementiadiagnosis,clinicaltrialsanddementiaservicedelivery.Hesaid:“Onethirdofuswillbedirectlyaffectedbydementiaatsomepointinourlives.Weneedtoadvanceourknowledgeateverypointalongthedementiapathwayfrombasicsciencetotheorganisationofclinicalservicestosupportpatientsandtheircarers.ThisisanexcellentopportunitytomakethishappeninSouthampton.”

RESEARCHING BIOFILMS IN INFANT FEEDING TUBES

ADDRESSING THE CHALLENGES IN DEVELOPING COUNTRIES

NEW RESEARCH CENTRE TO TACKLE DEMENTIA AND BRAIN AGEING

Institute for Life Sciences (IfLS) PhD student Chris Winnard’s research into the development of biofilms in neonatal nasogastric tubes has been going from strength to strength.

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The team is developing technologies to improve access to prosthetics.

Image: Team discussing infant feeding tubes in the Neonatal Unit, Princess Anne Hospital.

Image: Human arteries with amyloid (red) in Alzheimer’s disease.

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In Brief

Institute for Life Science (IfLS) PhD students work on novel interdisciplinary research projects with support from a supervisory team across the project disciplines. This supportive interdisciplinary environment, shaped by the IfLS and host faculties, creates a unique training and development experience for the next generation of leaders.

A sample of publications from our interdisciplinary postgraduate students: 2018-2019

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Health and Medicine

AshtonJJ,BorcaF, Mossotto E,CoelhoT,BatraA,AfzalNA,PhanHTT,StantonM,EnnisS&BeattieRM(2019).Increasedprevalenceofanti-TNFtherapyinpaediatricinflammatoryboweldiseaseisassociatedwithadeclineinsurgicalresectionsduringchildhood.Alimentary Pharmacology Therapeutics49(4),398–407.DOI:10.1111/apt.15094

Jevons LA, HoughtonFD&TareRS(2018).Augmentationofmusculoskeletalregeneration:roleforpluripotentstemcells.Regenerative Medicine 13(2),189-206.DOI:10.2217/rme-2017-0113

Scarpa E, JaneczekAA,HailesA,deAndrésMC,DeGraziaA,OreffoROC,NewmanTA&EvansND(2018).PolymersomenanoparticlesfordeliveryofWnt-activatingsmallmolecules.Nanomedicine 14(4),1267-1277.DOI:10.1016/j.nano.2018.02.014

Sri S, Pegasiou CM,CaveCA,HoughK,WoodN,Gomez-NicolaD,DeinhardtK,BannermanD,PerryVH&Vargas-CaballeroM(2019).Emergenceofsynapticandcognitiveimpairmentinamature-onsetAPPmousemodelofAlzheimer’sdisease.Acta Neuropathologica Communications 7,25.DOI:10.1186/s40478-019-0670-1

Sutton EJ,BradshawRT,OrrCM,FrendéusB,LarssonG,TeigeI,CraggMS,TewsI&EssexJW(2018).Evaluatinganti-CD32bF(ab)conformationusingmoleculardynamicsandsmall-angleX-Rayscattering.Biophysical Journal 115(2),289-299.DOI:10.1016/j.bpj.2018.03.040

Life Technologies

Anderson WJ,NowinskaK,HutterT,MahajanS&FischlechnerM(2018).Tuningplasmonslayer-by-layerforquantitativecolloidalsensingwithsurface-enhancedRamanspectroscopy.Nanoscale 10,7138-7146.DOI:10.1039/C7NR06656B

Boags AT,SamsudinF&KhalidS(2019).Bindingfrombothsides:TolRandfull-lengthOmpAbindandmaintainthelocalstructureoftheE coli cellwall.Structure27,713-724.e2.DOI:10.1016/j.str.2019.01.001

Boags AT,SamsudinF&KhalidS(2019).DetailsofhydrophobicentanglementbetweensmallmoleculesandBraun’slipoproteinwithinthecavityofthebacterialchaperoneLolA.Scientific Reports 9,3717.DOI:10.1038/s41598-019-40170-z

Moura CC,BourdakosKN,TareR,OreffoROC&MahajanS(2019).Live-imagingofbioengineeredcartilagetissueusingmultimodalnon-linearmolecularimaging.Scientific Reports 9,5561.DOI:10.1038/s41598-019-41466-w

Moura CC,LanhamSA,MonfortT,BourdakosKN,TareR,OreffoROC&MahajanS(2018).Quantitativetemporalinterrogationin3Dofbioengineeredhumancartilageusingmultimodallabel-freeimaging.Integrative Biology 10,635-645.DOI:10.1039/C8IB00050F

Núñez JA,GoringA,JavaheriB,RaziH,Gomez-NicolaD,HesseE,PitsillidesAA,ThurnerPJ,SchneiderP&ClarkinCE(2018).RegionaldiversityinthemurinecorticalvascularnetworkisrevealedbysynchrotronX-raytomographyandisamplifiedwithage.European Cells and Materials35,281-299.DOI:10.22203/eCM.v035a20

YangX,LennardKR,HeC,WalkerMC,BallAT,Doigneaux C,TavassoliA,&vanderDonkWA(2018).Alanthipeptidelibraryusedtoidentifyaprotein–proteininteractioninhibitor.Nature Chemical Biology 14,375–380.DOI:10.1038/s41589-018-0008-5

Living Systems

Ratto F,SimmonsBI,SpakeR,Zamora-GutierrezV,MacDonaldMA,MerrimanJC,TremlettCJ,PoppyGM,PehKS-H&DicksLV(2018).Globalimportanceofvertebratepollinatorsforplantreproductivesuccess:ameta-analysis.Frontiers in Ecology and the Environment 16(2),82-90.DOI:10.1002/fee.1763

Insights through Data

AshtonJJ,BonduelleQ,Mossotto E,CoelhoT,BatraA,AfzalNA,VadgamaB,EnnisS&BeattieRM(2018).Endoscopicandhistologicalassessmentofpaediatricinflammatoryboweldiseaseovera3-yearfollow-upperiod.Journal of Paediatric Gastroenterology and Nutrition 66(3),402-409.DOI:10.1097/MPG.0000000000001729

The Life Sciences Building

IfLS Student Publications 2018-19

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Page title

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AshtonJJ,BorcaF,Mossotto E, PhanHTT,EnnisS&BeattieRM(2018).Analysisandhierarchicalclusteringofbloodresultspriortodiagnosisinpaediatricinflammatoryboweldisease.Inflammatory Bowel Diseases izy369.DOI:10.1093/ibd/izy369

AshtonJJ,Mossotto E, EnnisS&BeattieRM(2019).Personalisingmedicineininflammatoryboweldisease—currentandfutureperspectives.Translational Pediatrics 8(1),56-69.DOI:10.21037/tp.2018.12.03

Lee KM,BiedermannS&MitraR(2018).Optimaldesignforexperimentswithpossiblyincompleteobservations.Statistica Sinica 28,1611-1632.DOI:10.5705/ss.202015.0225

Lee KM,BiedermannS&MitraR(2018).Optimaldesignwhenoutcomevaluesarenotmissingatrandom.Statistica Sinica 28,1821-1838.DOI:10.5705/ss.202016.0526

Lee KM,BiedermannS&MitraR(2019).D-optimaldesignsformultiarmtrialswithdropouts.Statistics in Medicine 38(15),2749-2766.DOI:10.1002/sim.8148

Mossotto E,AshtonJJ,O’GormanL,PengellyR,BeattieRM,MacArthurB&EnnisS(2019).GenePy-ascoreforestimatinggenepathogenicityinindividualsusingnext-generationsequencingdata.BMC Bioinformatics20,254.DOI:10.1186/s12859-019-2877-3

Testori M,HoyleR&EisenbarthH(2019).Howgroupcompositionaffectscooperationinfixednetworks:canpsychopathictraitsinfluencegroupdynamics?Royal Society Open Science 6,181329.DOI:10.1098/rsos.181329

Testori M, HarrisT,HoyleR&EisenbarthH(2019).TheeffectofpsychopathyoncooperativestrategiesinaniteratedPrisoner’sDilemmaexperimentwithemotionalfeedback.Scientific Reports9,2299.DOI:10.1038/s41598-019-38796-0

Wang T,BredeM,IanniA&MentzakisE(2018).Socialinteractionsinonlineeatingdisordercommunities:anetworkperspective.PLoS ONE13(7),e0200800.DOI:10.1371/journal.pone.0200800

Wang T, BredeM,IanniA&MentzakisE(2019).Characterizingdynamiccommunicationinonlineeatingdisordercommunities:amultiplexnetworkapproach.Applied Network Science 4,12.DOI:10.1007/s41109-019-0125-4

Wang T,MentzakisE,BredeM&IanniA(2019).EstimatingdeterminantsofattritionineatingdisordercommunitiesonTwitter:aninstrumentalvariablesapproach.Journal of Medical Internet Research 21(5),e10942.DOI:10.2196/10942

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Page title“Southampton’s mental health research

activity brings together doctors, psychologists, neuroscientists and health

scientists to deliver translational research that will positively impact on people’s lives.

Our expertise in child development, psychological interventions and affective neuroscience combine to deliver cutting

edge research that has the potential to improve mental health treatments and

wellbeing across the lifespan.”

Professor Matthew Garner Institute for Life Sciences and SoNG member

and Head of Psychology University of Southampton

“Globalchallengeswillonlybemetwhenresearchersworktogetherincross-disciplinarypartnerships.Ourfuture-lookingIfLSstudentshipschemefosterssuchcollaborationstodevelopthenextgenerationofresearchleaders.Weareimmenselyproudofouroutstandingstudentsandfullyexpectthemtobethemoversandshakersoftheirchosencareers.”

Professor Mandy Fader ProVice-Chancellor(InternalPartnerships)

Image: Changing Minds through Neuroscience Inspired Fashion is a collaboration between Peter Symonds College, the

University’s Winchester School of Art and the Southampton Neuroscience Group (SoNG) which aims to raise awareness of

mental health. Dress designed by Stephanie Orlowski. It is shaped like a butterfly with repeated prints of brain scans from

a stroke patient and is worn with a “cocoon” cape.

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Find out more: www.southampton.ac.uk/ifls

[email protected]+44(0)2380597280