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Ph.D.THESISDEFENSE

LinkingMassSpectrometryandGeneticsforStudyingtheVariousBiological

RolesofLipids

VanessaLinke

CoonGroup

Friday,May1st,2020at1:00PMhttps://us.bbcollab.com/guest/9d476a321cbf467a87261f93578f07c9

(orcallinat+1-571-392-7650PIN:3968644027)

Massspectrometry(MS)providesaccesstothequantitiesandidentitiesofbiomolecularactors,includingintheemergingfieldoflipidomics.Whilenotgeneticallyencoded,lipidsareinfluencedbythegenomethroughcomplexmetabolicnetworks.Here,IwillpresenttheconnectionofMStogenomicdatatofurthertheunderstandingofvariousmetabolicphenomenarangingfromaninvestigationofthemolecularbasisofthemicrobe-hostinteractiontothegeneticcausesofdiabetesandobesity.Iwillgiveanoverviewofthevarietyandfunctionsofmoleculesactinginmammalianorganisms,andthedetailsofMSasatooltomeasuretheirlevels.Thepresentedprojecttakesadvantageofthediversityoutbred(DO)mousemodelto broadly access genetic information via means of quantitative trait loci (QTL) mapping. As a firstapplication,wewillexplorethegeneticsofbileacidsandcecallipidsincontextofthegutmicrobiome.Bileacidsaremicrobially-derivedmetabolitesrecognizedfortheirsignalingfunctioninthehost.Thececallipidsweremeasuredinanuntargeted,i.e.discoveryway,thusallowingforrecognitionofunidentifiedfeaturesasmolecularactors,oneclassofwhichwereidentifiedasornithinelipids.Wewillthenfurtherdeveloptheideaofutilizinggeneticdatatoguideidentificationofsuchunidentifiedmassspectralfeaturesfromdiscoverylipidomicsprofilingofplasmaandliver.Lastly,Iwillconcludethefindingsandprovideanoutlookofexpandingthisstrategytootheromicsfeatures.

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