Expanding TOR Signaling by Phospho-proteogenomic Analysis of Saccharomyces cerevisiae Strain TB50a

Diplôme Thèse Expanding TOR Signaling by Phospho-proteogenomic Analysis of Saccharomyces cerevisiae Strain TB50a eng 2022-02-10 2022-02-18 author Martin Campos Maria Trinidad 0000-0003-3207-5413 814123 Trinidad Martin Campos director Loewith Robbie Joséph 630703 director Varesio Emmanuel 30230 164 10.13097/archive-ouverte/unige:159754 urn:nbn:ch:unige-1597544 Sc. 5637 The Target of Ramapycin (TOR) pathway controls cell growth in response to environmental stresses and nutrient availability. Mammalian TOR (mTOR) is implicated in several disorders, including cancer, obesity and diabetes. A better understanding of TOR may allow novel strategies in the treatment for mTOR-related diseases. In the present work we aimed to find new players in the TOR signaling pathways in the model yeast Saccharomyces cerevisiae. We have produced a high quality, whole genome sequence of Saccharomyces cerevisiae TB50, a strain used in our lab with a specific rapamycin-sensitive phenotype that makes it a perfect tool to study TOR signaling in yeast. Variant analysis and pooled-linkage analysis allowed us to pinpoint the causative variant responsible for this phenotype, a single missense mutation in the gene MKT1. Additionally, state-of-the-art quantitative phosphoproteomics with an allosteric inhibitor of TOR, rapamycin, and an ATP-competitive inhibitor, CMB4563, identified several potential TOR targets containing rapamycin-insensitive phosphosites. TOR Mass spectrometry TORC Phosphoproteomics Proteomics Bioinformatics Pooled-linkage analysis Dewey 570 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 false 814 Groupe Loewith e6b0188f-67d6-4eaa-afb8-5ae272bf3e95 Thesis Restricted Thesis_TrinidadMC.pdf 24845210 application/pdf 6f27e3e607ac80b224104256ebb9fdb2dec152c646f4043fbfc96a00e5164e3e restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire

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Expanding TOR Signaling by Phospho-proteogenomic Analysis of Saccharomyces cerevisiae Strain TB50a				2022	674	10

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Martin Campos, Trinidad

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