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ProtIG
is an NIH Special Interest Group (SIG)
that organizes seminars and workshops in relevant areas of proteomics,
including talks on separation and protein identification methods,
determination of post-translational modifications, protein-protein
interactions, and bioinformatics and data management. A monthly seminar
series is usually held at 12 pm
on the Second Thursday of each month (always check the Mtgs/Seminars
button on this page for these and other PROTIG announced meetings). To
receive email announcements of ProtIG events, join the listserv (Join the SIG
button on this page)
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November ProtIG Seminar |
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Thursday, November 14th, 2024 |
11:00 am - 12:00 pm ET |
NIH Building 50 |
Room 1227/1233 |
Aleksandra Nita-Lazar, Ph.D.
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Senior Investigator, Chief Functional Cellular Networks Laboratory of Immune System Biology National Institute of Allergy and Infectious Diseases National Institutes of Health
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“Signaling mechanisms and protein networks in innate immunity” |
Toll-like receptor (TLR) signaling in macrophages is essential for generating effective innate immune responses. Quantitative differences dependent on the dose and timing of the stimulus critically affect cell function and often involve proteins that are not components of widely shared transduction pathways. Mathematical modeling is an important approach to better understand how these signaling networks function in time and space. Wehave successfully modeled the S1P signaling pathway in macrophages using selected reaction monitoring (SRM) to measure the absolute abundance of the pathway proteins. The resulting values became parameters in a computational pathway model. To model the TLR signaling networks, we developed assays for the canonical TLR signaling pathway and related proteins and phosphoproteins and used parallel reaction monitoring (PRM) with heavy-labeled internal peptide standards to quantify protein and phosphorylated protein moleculenumbers per cell in untreated and LPS-stimulated macrophages. The absolute protein abundance values were entered into a model of the TLR pathway developed using Simmune, the rule-based modeling tool with a visual interface. To reach beyond basal level quantification, the TLR signaling network model is tested further and combined with global proteomic approaches to discover biologically important new proteins, protein complexes and PTMs involved in TLR and inflammasome pathways, of which some examples will be given. The protein and PTM levels are quantified in macrophages under diverse, but well-defined conditions (different TLR ligands, whole pathogens, and cells with mutations in specific signaling molecules). These data will allow to parameterize and test the TLR network model under a variety of conditions. Together, the interconnected projects will lead to the better understanding how the immune signaling pathways are regulated and activated during an infection. This research was supported by the Intramural Research Program of NIAID, NIH.
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This seminar will be videocast on
NIH Videocast
or
ZoomGov
Please mute your microphone and use the "raising hand" option to indicate a question.
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Seminars will be webcast online and available on the
Proteomics Interest Group website http://proteome.nih.gov as an archived presentation unless otherwise noted.
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