COBRE: Membrane Protein Production and Characterization

描述（由申请人提供）： COBRE关于膜蛋白生产和表征（COMPPAC）的动机是膜蛋白在生物学中的关键作用与这些分子的生产和结构表征中公认的缺陷之间的差异。我们将通过一套五个子项目，涉及七个PI从四个学科在所有教师队伍，与所有五个主要的PI无论是早期的职业生涯或初级调查员解决这一挑战。研究范围涵盖了从膜蛋白过表达，溶解和纯化，到基于晶体学表征的结构-功能研究，再到生物医学意义或相关膜蛋白的主要功能研究。要研究的膜蛋白跨越各种结构和功能特征，包括受体，粘附蛋白和界面酶，其相关性的几个生物医学上重要的条件，包括癌症，精子发生和化学战将被检查。COBRE将通过子项目内和子项目之间的合作而具有强烈的跨学科色彩，并且随着初始子项目获得独立支持，研究活动的范围将通过几个额外的活性膜蛋白研究实验室内的补充研究来扩大。为蛋白质生产、结构生物学和生物成像提供的核心设施支持与特拉华州大学和特拉华州生物技术研究所的生物分子研究的实质性基础设施密切结合。COBRE还将促进正在开发的方法在膜蛋白方面的系统应用，特别是在表达、纯化和结构生物学研究方面。这可能会对整个膜蛋白研究界产生重大影响，并对NIH路线图内正在开发的膜蛋白结构生物学国家基础设施产生重大影响。

DESCRIPTION (provided by applicant): The COBRE on Membrane Protein Production and Characterization (COMPPAC) is motivated by the disparity between the critical role of membrane proteins in biology and the well-recognized deficiencies in production and structural characterization of these molecules. We will address this challenge via a suite of five subprojects involving seven PIs from four academic disciplines at all faculty ranks, with all five of the lead PIs being either early-career or junior investigators. The scope of the research spans a spectrum from membrane protein overexpression, solubilization and purification, to structure-function studies based on crystallographic characterization, to predominantly functional studies of biomedically significant or related membrane proteins. The membrane proteins to be studied span a variety of structural and functional characteristics, including receptors, adhesion proteins and interfacial enzymes, and their relevance to several biomedically important conditions will be examined, including cancer, spermatogenesis and chemical warfare. The COBRE will have a strong interdisciplinary flavor by virtue of collaborations within and between subprojects, and as the initial subprojects acquire independent support, the scope of the research activities will be expanded by complementary research within several additional active membrane protein research labs. Core facilities support to be provided for protein production, structural biology and bioimaging is closely integrated with the substantial infrastructure for biomolecular research at the University of Delaware and the Delaware Biotechnology Institute. The COBRE will also foster the systematic application of the methods under development to membrane proteins in general, especially for the expression, purification and structural biology studies. This can have a significant impact on the membrane protein research community at large, and on the national infrastructure on membrane protein structural biology being developed within the NIH Roadmap.