Coupling protein dynamics and cell dynamics

耦合蛋白质动力学和细胞动力学

• 批准号: 1413256
• 负责人: Martin Gruebele
• 金额: $ 85.56万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1413256&HistoricalAwards=false
• 关键词: Coupling; protein; dynamics; cell

The broader goal of this research is to understand how crowding and the weak association of proteins in the live cell is used by cells to control its proteins. This project makes connection with many areas in physics, chemistry and cell biology. Thus, the undergraduate and graduate students supported by this research project come from many scientific backgrounds, and will acquire the knowledge and hands-on skills to advance US chemical technology and teaching in the area of molecular and cellular biophysics. Special efforts will also be made to disseminate the instrumentation technology resulting from this project, and create strong ties to researchers in the US and abroad. Thus the project will have impacts in biotechnology and instrumentation industry.The objective of this research project is to look inside single cells to see how their crowded environment affects the proteins and nucleic acids that keep the cell alive. Specific tasks are to find out how protein folding and movement inside cells interact, how the cell cycle controls protein folding, and how components of the spliceosome form inside cells from proteins and nucleic acids. The spliceosome cuts and rejoins our DNA so messenger RNA can be manufactured for making proteins. Humans could not live without it, yet we know virtually nothing about the biophysics of how its many protein and RNA pieces are assembled to do the job. As a final important task, the PI will look at an important industrial method that borrows the crowding idea from cells. So-called "PEGylation" enhances protein longevity by decorating proteins with stabilizing polymers, but the biophysical mechanism of stabilization remains unknown.

这项研究的更广泛的目标是了解活细胞中蛋白质的拥挤和弱结合是如何被细胞用来控制其蛋白质的。该项目涉及物理、化学和细胞生物学的多个领域。因此，这项研究项目支持的本科生和研究生来自许多科学背景，他们将获得推动美国分子和细胞生物物理领域的化学技术和教学的知识和实践技能。还将特别努力传播该项目产生的仪器技术，并与美国和海外的研究人员建立牢固的联系。因此，该项目将对生物技术和仪器工业产生影响。该研究项目的目标是观察单个细胞内部拥挤的环境是如何影响维持细胞存活的蛋白质和核酸的。具体任务是找出蛋白质在细胞内的折叠和运动是如何相互作用的，细胞周期是如何控制蛋白质折叠的，以及剪接体的成分是如何在细胞内由蛋白质和核酸形成的。剪接体切割并重新连接我们的DNA，因此信使RNA可以被制造出来制造蛋白质。人类没有它就无法生存，但我们几乎对它的生物物理学一无所知，即它的许多蛋白质和RNA片段是如何组装起来完成这项工作的。作为最后一项重要任务，PI将研究一种重要的工业方法，该方法借鉴了细胞拥挤的想法。所谓的“聚乙二醇化”通过用稳定的聚合物修饰蛋白质来提高蛋白质的寿命，但稳定的生物物理机制尚不清楚。