CENTER ON PROTEOLYTIC PATHWAYS(RMI)

这个子项目是许多利用 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。 描述（由申请人提供）：蛋白质水解对生物调节至关重要，其重要性因其不可逆性而被放大。蛋白质水解调节细胞行为的四个基本方面：分裂、死亡、分化和运动。蛋白水解途径是几乎每一种人类疾病病理学的关键，包括感染、炎症、血栓形成、癌症、肺气肿、阿尔茨海默氏症等。理解蛋白水解的重要性和影响是巨大的。实现这一最终目标将是一个巨大的挑战，需要作出雄心勃勃的协调努力。在这里，我们建议成立蛋白水解途径中心（CPP），这是一个研究蛋白酶、其抑制剂、其产物以及上游和下游调控途径的国家资源。CPP的战略目标是开发蛋白酶通路询问平台（PPIP）技术。该平台技术将由四项基础技术组成：（1）基于活性的蛋白酶分析，（2）蛋白酶活性成像技术，（3）产物末端同位素编码，以及（4）称为蛋白酶图谱的计算机环境。这个技术平台的一个关键和独特的功能是它直接关注测量活动，而不仅仅是丰富。CPP将包含一个培训部分，以确保新的科学家队伍接受培训，以最现代的技术和最尖端的技术来解决蛋白酶生物学问题。计划建立一个外联部分，以确保CPP实现高知名度，并最终与科研界建立众多联系。

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.