CAREER: An Innovative Study of Membrane Protein - Detergent Interactions

职业：膜蛋白与洗涤剂相互作用的创新研究

• 批准号: 0845668
• 负责人: Linda Columbus
• 金额: $ 68.47万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0845668&HistoricalAwards=false
• 关键词: CAREER; Innovative; Study; Membrane; Protein

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Membrane proteins are the gatekeepers of the cell and selectively mediate the flow of information and nutrients across the membrane (walls) of the cell. Membrane proteins are abundant (~25% of a typical genome). However, investigations of membrane proteins are considered "high-risk", predominantly because preparing protein samples is difficult due to their hydrophobic nature. Typically for structural and functional investigations, membrane proteins are extracted from the native cell membrane with detergent micelles. Detergents are empirically screened to solubilize and stabilize the membrane proteins because of a lack in the understanding of how detergents mimic the cell membrane and stabilize a membrane protein fold. The screening process is expensive and time-consuming, and limits the progress of membrane protein investigations. This research aims to overcome these hindrances by (1) establishing a fundamental understanding of protein-detergent interactions and (2) assessing the impact these interactions have on membrane protein structure and stability. Broader ImpactsEfforts to impact the broader community are focused primarily on the encouragement and confidence building of middle school and college age female and underrepresented groups in the area of chemistry. At the undergraduate level, a new biochemistry curriculum was introduced that stepped away from textbook learning and moved towards inquiry and research based learning. Also, one-on-one and group mentorship programs such as a lunch series have been implemented. For middle school girls, two avenues have been pursued (1) interactive one hour programs were created that introduce chemistry to middle school girls through outreach programs such as the University of Virginia Young Woman Leadership Program and (2) three hour interactive demos and tours of chemistry laboratories at the University of Virginia hosted by female faculty, graduate students, and postdoctoral fellows were designed for local schools such as The Village School (an all girls middle school).

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。膜蛋白是细胞的守门人，并选择性地介导信息和营养物质穿过细胞膜（壁）的流动。膜蛋白是丰富的（约25%的典型基因组）。然而，膜蛋白的研究被认为是“高风险”的，主要是因为蛋白质样品的制备是困难的，由于它们的疏水性。通常对于结构和功能研究，用去污剂胶束从天然细胞膜中提取膜蛋白。由于缺乏对去污剂如何模拟细胞膜和稳定膜蛋白折叠的理解，因此根据经验筛选去污剂以溶解和稳定膜蛋白。筛选过程昂贵且耗时，限制了膜蛋白研究的进展。本研究旨在通过（1）建立对蛋白质-去污剂相互作用的基本理解和（2）评估这些相互作用对膜蛋白结构和稳定性的影响来克服这些障碍。更广泛的影响影响更广泛社区的努力主要集中在鼓励和建立中学和大学年龄女性以及化学领域代表性不足的群体的信心。在本科阶段，引入了一个新的生物化学课程，从课本学习转向探究和研究型学习。此外，还实施了一对一和小组辅导方案，如午餐系列。 对于中学女生来说，有两种途径：（1）创建了一个小时的互动节目，通过弗吉尼亚大学年轻女性领导力节目等外联节目向中学女生介绍化学;（2）弗吉尼亚大学由女教师、研究生、和博士后研究员是为当地学校设计的，如乡村学校（一所女子中学）。