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SUMMARY:A Mycobacterium tuberculosis Protein Atlas
DTSTART:20191204T103000
DTEND:20191204T113000
DTSTAMP:20260610T155106Z
UID:4bdbb7c7ad3d39dfd36246054fb297d9648c5e911ca1c4db93c894f3
CATEGORIES:Conferences - Seminars
DESCRIPTION:Amir Banaei-Esfahani\, Institute of Molecular Systems Biology\
 , ETH Zurich (CH)\nSEMINAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTR
 ITION ALLIANCE (LIMNA)\n\nAbstract:\nTuberculosis is caused by Mycobacteri
 um tuberculosis (Mtb) and claims 1.8 million lives annually. Clinical stra
 ins of Mtb reveal diverse phenotypes that are largely determined by the st
 ate of the proteome. Therefore\, the model strain H37Rv that has been used
  for most studies in the field does not represent the full genomic and phe
 notypic diversity of Mtb. Here\, we aim to identify master regulators that
  control the Mtb proteome of genetically diverse strains driving different
  phenotypes in two conditions.\nSWATH-MS profiled the proteome of 70 clini
 cal strains of Mtb cultivated under normal and nitric oxide stress\, a maj
 or bactericidal agent within macrophages. Moreover\, we fully sequenced th
 e genome of the respective strains. Six strains were subjected to transcri
 ptional measurements.\nWe quantified ~2700 proteins corresponding to ~80% 
 of the expressed genes\, reproducibly across the large Mtb sample cohort. 
 To address the aim of the project\, we developed two exploratory computati
 onal frameworks\, a genome-scale transcriptional model and dysregulation a
 nalysis for protein complexes\, and analyzed the generated dataset using t
 hose two pipelines as well as QTL mapping. The data indicated that the bas
 al expression and response of various protein functional groups such as Id
 eR and DosR regulon significantly differ between Mtb lineages. Twenty-eigh
 t transcription factors orchestrating the Mtb transcriptional network betw
 een lineages have been identified. Several subnetworks are regulated diffe
 rently in terms of their stoichiometry across various lineages including t
 he protein association Rv0068-Rv2187. QTL analysis\, implemented for the f
 irst time in bacteria\, revealed that a single mutation in KstR affects th
 e expression of its seven targets involved in cholesterol metabolism\, the
  main carbon source during Mtb infection. It further provided the first ev
 idence of the existence of protein isoforms in Mtb. We have shown that gen
 omic differences between the clinical isolates determine the state of the 
 proteome and mediate different clinically relevant phenotypes.\n\nAmir Ban
 aei-Esfahani 1\, 2 \, Julia Feldmann 3 \, Lukas Folkman 4 \, Sonia Borrell
  3 \, Andrej Trauner 3 \, Karsten Borgwardt 4 \, Ben Collins 1 \, Sebastie
 n Gagneux 3 \, Rudolf Aebersold 1\, 5\n\n1 Institute of Molecular Systems 
 Biology\, ETH Zurich\, Zurich\, Switzerland\n2 PhD Program in Systems Biol
 ogy\, University of Zurich and ETH Zurich\, Zurich\, Switzerland\n3 Depart
 ment of Medical Parasitology and Infection Biology\, Swiss Tropical and Pu
 blic Health Institute\, Basel\, Switzerland\n4 Department of Biosystems Sc
 ience and Engineering\, ETH Zurich\, Basel\, Switzerland\n5 Faculty of Sci
 ence\, University of Zurich\, Zurich\, Switzerland\n\n 
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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