Biophysical Analysis of Chaperone Influences on Membrane Protein Folding

伴侣分子对膜蛋白折叠影响的生物物理分析

• 批准号: 0919868
• 负责人: Karen Fleming
• 金额: $ 117.27万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0919868&HistoricalAwards=false
• 关键词: Biophysical; Analysis; Chaperone; Influences; Membrane

This project investigates membrane-protein folding, an essential function of all cells across all kingdoms of life. The project's overall goal is to understand how cells accomplish the task of folding their membrane proteins by measuring the conformations and interactions accessible to these molecules as they undergo the folding reaction. The experiments adopt the time-tested biophysical techniques and mathematical theories established by decades of research on soluble protein folding. These tools will be applied in novel ways to eight membrane proteins to determine how they fold. The project further investigates the functional roles of important cellular factors known as chaperones. These are soluble proteins that are required for membrane protein folding in vivo, yet the physical nature of how they do this is yet undiscovered. Altogether, this project will address original and fundamental questions about how the membrane parts of a cell are assembled and regulated.The principal investigator (PI) will facilitate broader outreach in several venues: (1) In the community-at-large the PI will tutor middle school students in science and math and will welcome opportunities to discuss science and scientific careers with K-12 students; (2) In the scientific community the PI will facilitate outreach through organizing scientific conferences, mentoring young scientists, and disseminating research results by invited talks; (3) In the classroom the PI will improve pedagogical tools that utilize discovery-based knowledge and methods; and (4) the PI will mentor undergraduate and graduate student researchers. All students will have the opportunity to present their work at national scientific meetings and will publish their results in peer-reviewed journals.

该项目研究膜蛋白折叠，这是所有生命王国中所有细胞的基本功能。该项目的总体目标是通过测量这些分子在经历折叠反应时的构象和相互作用，了解细胞如何完成折叠膜蛋白的任务。这些实验采用了经过时间考验的生物物理技术和数十年可溶性蛋白质折叠研究建立的数学理论。这些工具将以新颖的方式应用于八种膜蛋白，以确定它们如何折叠。该项目进一步研究了被称为伴侣的重要细胞因子的功能作用。这些是体内膜蛋白折叠所需的可溶性蛋白质，但它们如何折叠的物理性质尚未被发现。总而言之，该项目将解决有关细胞膜部分如何组装和调节的原始和基本问题。首席研究员 (PI) 将在多个场所促进更广泛的推广：(1) 在整个社区，PI 将辅导中学生科学和数学，并欢迎有机会与 K-12 学生讨论科学和科学职业； (2) 在科学界，PI将通过组织科学会议、指导年轻科学家以及通过邀请演讲传播研究成果来促进推广； (3) 在课堂上，PI 将改进利用基于发现的知识和方法的教学工具； (4) PI 将指导本科生和研究生研究人员。所有学生将有机会在全国科学会议上展示他们的工作，并在同行评审的期刊上发表他们的成果。