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SUMMARY:Quantitative Dissection of Protein Dynamics in the Immune System
DTSTART:20150423T150000
DTSTAMP:20260531T005623Z
UID:8cb234f280199ffd7b0f67b3943425364e7d9c6906856fceb736f8ea
CATEGORIES:Conferences - Seminars
DESCRIPTION:Marko Jovanovic\, Ph.D.\, Regev Lab\, Broad Institute of MIT a
 nd Harvard\, Cambridge\, MA (USA)\nBIOENGINEERING SEMINARAbstract:\nGene e
 xpression is tightly controlled from transcription to protein degradation.
  Although the mammalian genome encodes >1500 RNA binding and translation-a
 ssociated proteins (RBPs)\, most systematic approaches focused on changes 
 in mRNA abundance. We developed new experimental and computational strateg
 ies to study the regulation of protein production in dynamic systems\, and
  applied them to the response of primary dendritic cells (DCs) to pathogen
 s. First\, we combined measurements of protein production and degradation 
 and RNA dynamics to build a quantitative\, genome-scale model of the diffe
 rential regulation of gene expression in LPS stimulated primary DCs. We fo
 und that upon LPS stimulation\, changes in RNA abundance play a dominant r
 ole in determining most dynamic fold changes in protein levels. In contras
 t\, the preexisting proteome of proteins performing basic cellular functio
 ns is remodeled primarily through changes in protein production or degrada
 tion. Next\, to help determine which genes regulate such expression change
 s\, we adapted the new CRISPR technology to develop a marker based genome-
 wide CRISPR screen in DCs from a new Cas9-transgenic mouse. In this screen
 \, DCs are infected with a genome wide lentiviral library of sgRNAs\, stim
 ulated with LPS\, and monitored by intra-cellular staining for the anti-in
 flammatory cytokine TNF-α. We successfully discover near-complete known p
 athways of the LPS response as well as many new candidates\, especially in
  complexes regulating protein modification or chromatin biology not previo
 usly implicated in the response. This work provides a systematic framework
  to dissect gene expression regulation that I will leverage to understand 
 the role of RBPs and the ribosome in protein production.Bio:\nsince Sep 20
 11 Postdoctoral Fellow in the laboratory of Prof. Aviv Regev\, Broad Insti
 tute of MIT and Harvard\, USA\nOct 2009 –Sep 2011 Postdoctoral Fellow in
  the laboratory of Prof. Michael O. Hengartner\, Institute of Molecular Li
 fe Sciences\, University of Zurich\n2009: Doctor of Philosophy (Ph.D.) - g
 raduation at the University of Zurich\n2005 - 2009: Ph.D. Studies in Molec
 ular Biology at the University of Zurich\, Switzerland\n2004: Master of Sc
 ience (M.Sc.) - graduation at the University of Vienna\n2000 – 2004: Stu
 dies of Molecular Biology at the University of Vienna\, Austria
LOCATION:SV1717a http://map.epfl.ch/?room=sv1717a
STATUS:CONFIRMED
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