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Ph.D. THESIS DEFENSE Linking Mass Spectrometry and Genetics for Studying the Various Biological Roles of Lipids Vanessa Linke Coon Group Friday, May 1 st , 2020 at 1:00 PM https://us.bbcollab.com/guest/9d476a321cbf467a87261f93578f07c9 (or call in at +1-571-392-7650 PIN: 396 864 4027) Mass spectrometry (MS) provides access to the quantities and identities of biomolecular actors, including in the emerging field of lipidomics. While not genetically encoded, lipids are influenced by the genome through complex metabolic networks. Here, I will present the connection of MS to genomic data to further the understanding of various metabolic phenomena ranging from an investigation of the molecular basis of the microbe-host interaction to the genetic causes of diabetes and obesity. I will give an overview of the variety and functions of molecules acting in mammalian organisms, and the details of MS as a tool to measure their levels. The presented project takes advantage of the diversity outbred (DO) mouse model to broadly access genetic information via means of quantitative trait loci (QTL) mapping. As a first application, we will explore the genetics of bile acids and cecal lipids in context of the gut microbiome. Bile acids are microbially-derived metabolites recognized for their signaling function in the host. The cecal lipids were measured in an untargeted, i. e. discovery way, thus allowing for recognition of unidentified features as molecular actors, one class of which were identified as ornithine lipids. We will then further develop the idea of utilizing genetic data to guide identification of such unidentified mass spectral features from discovery lipidomics profiling of plasma and liver. Lastly, I will conclude the findings and provide an outlook of expanding this strategy to other omics features.

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Page 1: Ph.D. THESIS DEFENSE - UW-Madison Chemistry Linke... · Microsoft Word - Vanessa Linke_Thesis Defense.docx Created Date: 4/28/2020 8:53:42 PM

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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