Research Project 1: Systems level complexity of ITAM signaling

$258,571P50FY2014GMNIH

University Of New Mexico Health Scis Ctr, Albuquerque NM

Investigators

Linked publications & trials

Paper 38593442 Paper 37870221 Paper 37515324 Paper 37461622 Paper 36827414 Paper 36698655 Paper 36418347 Paper 36200848 Paper 36081774 Paper 35793126 Paper 35674895 Paper 35482702 Paper 34880301 Paper 34821550 Paper 34174403 Paper 33863729 Paper 33586761 Paper 33508018 Paper 33413202 Paper 32913056 Paper 32649863 Paper 32484803 Paper 32474079 Paper 32322610 Paper 32203165 Paper 32049328 Paper 31964711 Paper 31913761 Paper 31908021 Paper 31813797 Paper 31344967 Paper 31311408 Paper 31263465 Paper 31216232 Paper 31086024 Paper 30982634 Paper 30916347 Paper 30532647 Paper 30465885 Paper 30301787 Paper 30261690 Paper 30169528 Paper 30157435 Paper 30133344 Paper 30093900 Paper 30055413 Paper 30042128 Paper 29855542 Paper 29746086 Paper 29594824 Paper 29420192 Paper 29401455 Paper 29378725 Paper 29328918 Paper 29296828 Paper 29232689 Paper 29169987 Paper 29156664 Paper 29138425 Paper 29109206 Paper 29044117 Paper 28988771 Paper 28978808 Paper 28855374 Paper 28678440 Paper 28428953 Paper 28056142 Paper 28045041 Paper 28039304 Paper 27932448 Paper 27899526 Paper 27751944 Paper 27721497 Paper 27711232 Paper 27698445 Paper 27595041 Paper 27570763 Paper 27490268 Paper 27417454 Paper 27375939 Paper 27176323 Paper 26990103 Paper 26920246 Paper 26797147 Paper 26792838 Paper 26724083 Paper 26719526 Paper 26633712 Paper 26592446 Paper 26556387 Paper 26542716 Paper 26470790 Paper 26378253 Paper 26337388 Paper 26304724 Paper 26206334 Paper 26178138 Paper 26099197 Paper 26061425 Paper 25992915

Abstract

Project 1: Systems level complexity of ITAM signaling Project PI: Wilson Summary Important immunoreceptors of T cells, B cells, mast cells, basophils, dendritic cells and other immune cells bear ITAMs (Immuno Tyrosine-Based Activation Motif) in their cytoplasmic tails. After tyrosine phosphorylation by Src kinases, phospho-ITAMs recruit Syk/ZAP-70 kinases to propagate positive signaling associated with key adaptive and innate immune functions. In this project, STMC investigators apply a multiscale systems biology approach to evaluate the contributions of spatial organization and ligand multivalency on ITAM receptor signal initiation and output. The model system for Aim 1 is the high affinity receptor for receptor (FceRI) on mast cells and basophils. An innovative focus is on natural allergens, based on experiments in human basophils from atopic subjects. Aim 2 is centered on the C-type lectin receptor, Dectin-1, that recognizes fungal pathogens. High resolution microscopy methods, coupled with quantitative evaluation of ligand- mediated aggregation, are novel features of both experimental aims. The research plan incorporates extensive computational modeling, including molecular structure/dynamics and simulations of cellular signal transduction. Mathematical models will provide predictions to be tested through the innovative application of powerful quantitative fluorescence, electron microscopy and molecular engineering methods.

View original record on NIH RePORTER →