DEVELOPMENT OF FLOW CYTOMETRY BASED PROTEASE MODEL SYSTEMS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 金属蛋白酶是包括B在内的许多致病菌毒性的主要因素。anthracis，C.肉毒杆菌和C.破伤风。 详细了解完整的动力学机制和影响这些蛋白酶的位点特异性的因素，将显着提高我们的能力，筛选和设计特定的毒性金属蛋白酶的抑制剂，可能用作治疗。 这种理解也将有助于建立敏感的生物威胁检测分析，这将对国土防御产生重大影响。 该项目将开发一个基于流式细胞术的模型系统，该系统将允许确定金属蛋白酶的详细动力学机制，影响位点特异性的因素，并为抑制剂筛选提供框架。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Metalloproteases are a major factor in the toxicity of many pathogenic bacteria including B. anthracis, C. botulinum, and C. tetani. A detailed understanding of the complete kinetic mechanism and factors affecting the site specificity of these proteases will significantly improve our ability to screen and design specific inhibitors of toxic metalloproteases for possible use as therapeutics. Such understanding will also facilitate the creation of sensitive biothreat detection assays that would have a significant impact on homeland defense. This project will develop a flow cytometry based model system that will allow the determination of the detailed kinetic mechanism of a metalloprotease, factors affecting site specificity, and provide a framework for inhibitor screening.