Formation and biological activity of functional protein aggregates

功能蛋白聚集体的形成和生物活性

• 批准号: 1517231
• 负责人: Eric Ross
• 金额: $ 59.55万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1517231&HistoricalAwards=false
• 关键词: Formation; biological; activity; functional; protein

Title: Formation and biological activity of functional protein aggregatesThe interior of cells contains high concentrations of protein. Cells have complex systems to prevent these proteins from aggregating. However, recent evidence has shown that the aggregation of specific proteins is used to regulate various important cellular functions. In this research project, the investigators will use a combination of genetic, biochemical and computer modeling techniques to develop improved methods to predict this particular protein aggregation, and to examine how such aggregates are used to regulate cellular functions. This project will offer diverse interdisciplinary training to junior scientists. A portion of the research will be conducted in the context of a novel laboratory course, which is designed to be a hybrid of independent research and traditional laboratory classes. This course will allow students to generate new, publishable research, but in a sufficiently structured setting to allow for training of a large number of students. Additionally, the PI will continue to expand his "Biochemistry is Elementary" outreach program. This program introduces elementary school students to the scientific process and to basic concepts in biochemistry using exciting, hands-on activities.Despite the growing realization of the importance of prions and prion-like aggregation in normal cellular physiology, the exact basis for and regulation of these aggregation events are poorly understood. In this project, the investigators will utilize a combination of genetic, biochemical and computer modeling techniques to develop improved methods to predict prion-like aggregation and to examine how prion-like aggregation of RNA binding proteins affects the formation of cytoplasmic RNA-protein granules. The first goal is to develop better tools to predict prion aggregation and to predict how protein modifications affect prion activity. These studies will generate new resources to facilitate searches for new prion-like elements, and will provide key insight into the regulation of prion-like aggregation. The second goal of the project is to examine the role of prion-like domains in the formation of cytoplasmic RNA-proteins granules. These studies will provide a framework for studying functional protein aggregation, while offering insight into the role of prion-like aggregation in post-transcriptional regulation of gene expression.

关键词：蛋白质;功能性蛋白质;聚集体;生物活性;细胞内部含有高浓度的蛋白质。 细胞有复杂的系统来防止这些蛋白质聚集。然而，最近的证据表明，特定蛋白质的聚集用于调节各种重要的细胞功能。在这个研究项目中，研究人员将使用遗传，生物化学和计算机建模技术的组合来开发改进的方法来预测这种特定的蛋白质聚集，并研究这些聚集体如何用于调节细胞功能。 该项目将为年轻科学家提供多样化的跨学科培训。研究的一部分将在一个新的实验室课程的背景下进行，该课程旨在成为独立研究和传统实验室课程的混合体。 本课程将允许学生产生新的，可扩展的研究，但在一个充分结构化的设置，以允许大量的学生培训。 此外，PI将继续扩大他的“生物化学是基本的”外展计划。 该项目通过令人兴奋的实践活动向小学生介绍科学过程和生物化学的基本概念。尽管人们越来越认识到朊病毒和朊病毒样聚集在正常细胞生理学中的重要性，但这些聚集事件的确切基础和调节仍知之甚少。在这个项目中，研究人员将利用遗传，生物化学和计算机建模技术的组合来开发改进的方法来预测朊病毒样聚集，并研究RNA结合蛋白的朊病毒样聚集如何影响细胞质RNA蛋白颗粒的形成。第一个目标是开发更好的工具来预测朊病毒聚集和预测蛋白质修饰如何影响朊病毒活性。这些研究将产生新的资源，以促进新的朊病毒样元素的搜索，并将提供关键的洞察朊病毒样聚集的调节。该项目的第二个目标是研究朊病毒样结构域在细胞质RNA蛋白颗粒形成中的作用。这些研究将为研究功能性蛋白质聚集提供一个框架，同时提供深入了解朊病毒样聚集在基因表达的转录后调控中的作用。