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Granule exocytosis and neutrophil activation

颗粒胞吐作用和中性粒细胞激活

基本信息

批准号：
7589011
负责人：
Silvia M Uriarte
金额：
$ 12.91万
依托单位：
UNIVERSITY OF LOUISVILLE
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：
2009-03-01 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7589011
关键词：
Acute Acute Lung Injury Address Adherence Air Animal Model Arts C-terminal Cell membrane Cellular biology Chemotaxis Chimeric Proteins Coiled-Coil Domain Computer software Cytoplasmic Granules Data Databases Docking Event Exocytosis Funding Gelatinases Generations Goals Human Immunoprecipitation Inflammation Inflammatory Response Intracellular Membranes Learning Mass Spectrum Analysis Mediating Membrane Membrane Fusion Membrane Protein Traffic Mentors Methodology Modeling Molecular Molecular Biology N-terminal Natural Immunity Neutrophil Activation Normal tissue morphology Peptide Hydrolases Peptides Phagocytosis Phase Phosphorylation Plasmids Post-Translational Protein Processing Proteins Proteomics Rattus Reactive Oxygen Species Regulation Research Personnel Respiratory Burst Role SNAP receptor Secretory Vesicles Site State Interests Stimulus Techniques Technology Tertiary Protein Structure Testing Tissues Training Vesicle abstracting base effusion experience extracellular in vitro testing in vivo killings neutrophil novel strategies prevent receptor response skills syntaxin

项目摘要

DESCRIPTION (provided by applicant): The postulated role of exocytosis in mediating various functional responses associated with neutrophil activation has not been directly tested. We will use a novel approach; generating TAT-fusion proteins containing the coiled-coil domains of different SNARE proteins; to test the hypothesis that blocking exocytosis of distinct granule subsets will prevent specific neutrophil phenotypic changes and this strategy may be used to prevent neutrophil-mediated tissue damage in vivo. The specific objectives of the mentored phase of this proposal are: 1) to determine the ability of TAT-fusion proteins containing the SNARE domains of SNAP-23, syntaxins, and VAMPs to inhibit exocytosis of each of the four neutrophil granule subsets. The training goal of this aim is to develop molecular biology and cell biology skills that will allow the applicant to address experimental questions at new levels and apply them in the independent phase of this proposal. 2) To determine the most effective way to administer the TAT-SNARE fusion proteins in vivo and to determine the effect of these fusion proteins on models of acute neutrophil-dependent inflammation in rats. The training goals of this aim are to learn animal models of neutrophil-dependent inflammation, and to establish the ability of TAT-fusion proteins to inhibit neutrophil exocytosis in vivo. 3) Define other proteins that interact with SNARE proteins by proteomic analysis. The training goal of this aim is to develop the ability to perform proteomic analysis. The state-of-the-art techniques acquired during the mentored phase will greatly increase the expertise that will allow the PI to become a successful independent investigator. For the independent phase the specific objectives are: 1) To determine the specific functional responses that are regulated by neutrophil granule exocytosis; 2) To define the mechanisms by which inhibition of neutrophil exocytosis in vivo blocks the inflammatory response; and 3) To investigate the molecular mechanisms by which exocytosis is stimulated. The training the applicant will receive will make her unique in the combination of experience, interest, and state-of-the-art technology and will maximize her potential to become an independent NIH-funded investigator. (End of Abstract)

描述（由申请人提供）：