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Research Project 1: Systems level complexity of ITAM signaling

研究项目 1：ITAM 信令的系统级复杂性

基本信息

批准号：
9118197
负责人：
Bridget S Wilson
金额：
$ 25.34万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9118197
关键词：
Ablation Accounting Address Affinity Allergens Allergic Antigens B-Lymphocytes Basophils Behavior Binding Biochemistry Biological Models Biophysics C Type Lectin Receptors Candida Candidiasis Cell Wall Cell membrane Cells Complex Computer Simulation Coupled Cytoplasmic Tail Dendritic Cells Dependence Diffusion Dimerization Docking Electron Microscopy Engineering Epitopes Event Experimental Models Faculty Family Fluorescence Fungal Components Genetic Geometry Glucans Hematogenous Histamine Release Human IgE IgE Receptors Immune Immune Cell Activation In Vitro Inflammation Mediators Inflammatory Response Pathway Leukocytes Ligands Masks Measures Mediating Mediator of activation protein Methods Microscopy Modeling Molecular Molecular Models Molecular Structure Mus Mutagenesis Mutation Mycoses Nanoscopy Natural Immunity Optics Output Phagocytosis Phosphotransferases Polysaccharides Population Predisposition Process Production Quantitative Evaluations Receptor Signaling Recruitment Activity Regulation Research Research Personnel Research Project Grants Resolution Risk Role Running Signal Transduction Solubility Stimulus Structure Structure-Activity Relationship Surface System Systems Biology T-Lymphocyte Technology Testing Time Tyrosine Tyrosine Phosphorylation Ursidae Family Work ZAP-70 Gene allergic response base crosslink dectin 1 design experience immune function immunogenic innate immune function innovation interest mast cell mathematical model member molecular modeling nanoscale novel pathogen prevent programs protein aggregation receptor research study response simulation spatiotemporal src-Family Kinases sugar

项目摘要

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.

项目1：ITAM信令的系统级复杂性项目PI：Wilson 总结 T细胞、B细胞、肥大细胞、嗜碱性粒细胞、树突状细胞等免疫细胞的重要免疫受体在它们的胞质尾中带有ITAM（基于免疫酪氨酸的激活基序）。酪氨酸磷酸化后通过Src激酶，磷酸化ITAM募集Syk/ZAP-70激酶来传播与以下相关的正信号：关键的适应性和先天免疫功能。在这个项目中，STMC研究人员应用了一个多尺度系统，生物学方法来评估ITAM受体的空间组织和配体多价性的贡献信号启动和输出。针对Aim 1的模型系统是细胞上的受体的高亲和力受体（FceRI）。肥大细胞和嗜碱性粒细胞。一个创新的重点是天然过敏原，基于人体实验，嗜碱性粒细胞。目的2是集中在C型凝集素受体，Dectin-1，识别真菌病原体高分辨率显微镜方法，配体的定量评价，加上- 介导的聚集是两个实验目的的新特征。该研究计划包括广泛的计算建模，包括分子结构/动力学和细胞信号转导的模拟。数学模型将提供预测，通过创新应用强大的定量荧光、电子显微镜和分子工程方法。