CENTER ON PROTEOLYTIC PATHWAYS(RMI)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 描述(申请人提供)：蛋白质分解对生物调节至关重要，其重要性被放大，因为它是不可逆转的。蛋白质分解调节细胞行为的四个基本方面：分裂、死亡、分化和运动。蛋白质分解途径是几乎所有类型人类疾病的关键，包括感染、炎症、血栓形成、癌症、肺气肿、阿尔茨海默氏症等。从整体上理解蛋白质分解作用的重要性和影响将是巨大的。实现这一最终目标将是一项相当大的挑战，需要雄心勃勃和协调一致的努力。在这里，我们建议成立蛋白分解途径中心(CPP)，这是一个研究蛋白酶、它们的抑制剂、它们的产物以及上下游调控途径的国家资源。CPP的战略目标是开发蛋白质途径询问平台(PPIP)技术。这一平台技术将由四项基础技术组成：(1)基于活动的蛋白酶图谱，(2)蛋白酶活性成像技术，(3)产品终端同位素编码，(4)在电子环境中称为蛋白酶图谱。这个技术平台的一个关键和独特的特点是，它直接关注衡量活动，而不是仅仅衡量丰富度。CPP将包含一个培训部分，以确保培训一支新的科学家队伍，用最现代的技术和最尖端的技术处理蛋白酶生物学。计划设立一个外联部分，以确保国家方案方案与科学研究界建立高度的知名度，并最终建立众多联系。

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. DESCRIPTION (provided by applicant): Proteolysis is of paramount importance to biological regulation, and its significance is magnified because it is irreversible. Proteolysis regulates the four fundamental aspects of cell behavior; division, death, differentiation and motility. Proteolytic pathways are key to the pathology of virtually every type of human disease including, infection, inflammation, thrombosis, cancer, emphysema, Alzheimer's, etc. The importance and impact of understanding proteolysis "in total" will be immense. Achieving this ultimate goal will be a considerable challenge, and one that will require an ambitious and coordinated effort. Here we propose to form the Center on Proteolytic Pathways (CPP), a National Resource for the study of proteases, their inhibitors, their products, and upstream and downstream regulatory pathways. The strategic goal of the CPP is to develop The Protease Pathway Interrogation Platform (PPIP) technology. This platform technology will be comprised of four foundation technologies; (1) Activity-based Protease Profiling, (2) Protease Activity Imaging Technology, (3) Product Terminal Isotope Coding, and (4) the in silico environment called Protease Map. A key and unique feature of this technology platform is its focus squarely on measuring activity, as opposed to just abundance. The CPP will contain a Training component to ensure that a new cadre of scientists is trained to tackle protease biology with the most modem of techniques and most cutting edge technology. An Outreach component is planned to ensure that the CPP achieves high visibility, and ultimately numerous connections, with the scientific research community.