CAREER: Small-Molecule-Regulated Signaling Proteins

职业：小分子调节信号蛋白

• 批准号: 0954242
• 负责人: Dustin Maly
• 金额: $ 65万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0954242&HistoricalAwards=false
• 关键词: CAREER; Small; Molecule; Regulated; Signaling

This award in the Chemistry of Life Processes program of the Chemistry Division is co-funded by the Cell cluster in the Division of Molecular and Cellular Biosciences. The award supports work by Professor Dustin Maly at the University of Washington in Seattle to engineer mammalian signaling enzymes that can be regulated with cell-permeable small molecules. Conversion of external stimuli into complex cellular behaviors is mediated by networks of interacting multi-domain signaling enzymes. The use of engineered signaling enzymes that can be controlled in a rapid, reversible and dose-dependent manner with small molecules in living cells allows the roles of individual proteins and proteins domains in specific signaling events to be determined. Uncovering the roles and contributions of components in these networks provides insight into aberrant cellular phenotypes and facilitates efforts to rationally engineer cells with novel behaviors. The interdisciplinary nature of this research allows the participation of undergraduate and graduate students with diverse scientific interests. Furthermore, this research program serves as a vital scientific link between the University of Washington and local area high schools that contain large populations of disadvantaged and under-represented students. External information is converted into complex cellular behaviors such as growth, differentiation and motility by networks of signaling enzymes. By re-engineering signaling enzymes from simple modules and observing the effects of these synthetic proteins on cellular behavior, it will be possible to uncover the core design principles behind complex biological systems. Determining the roles and contributions of the proteins involved in specific signaling events provides an understanding of the molecular wiring of cells. Furthermore, determining the logic of signal transduction networks facilitates the rational engineering of cells with unique phenotypic behaviors.

该奖项由分子和细胞生物科学部的细胞团共同资助，由化学部生命过程化学项目颁发。该奖项支持西雅图华盛顿大学的达斯汀·马利教授的工作，他设计了一种哺乳动物信号酶，这种酶可以通过细胞渗透的小分子来调节。外界刺激转化为复杂的细胞行为是由相互作用的多域信号酶网络介导的。利用工程化的信号酶可以快速、可逆和剂量依赖的方式控制活细胞中的小分子，从而可以确定单个蛋白质和蛋白结构域在特定信号事件中的作用。揭示这些网络中组件的作用和贡献有助于深入了解异常的细胞表型，并有助于合理设计具有新行为的细胞。这项研究的跨学科性质允许具有不同科学兴趣的本科生和研究生参与。此外，这项研究计划是华盛顿大学和当地高中之间至关重要的科学纽带，当地高中有大量的弱势学生和代表不足的学生。外部信息通过信号酶网络转化为复杂的细胞行为，如生长、分化和运动。通过重新设计简单模块中的信号酶，并观察这些合成蛋白质对细胞行为的影响，将有可能揭示复杂生物系统背后的核心设计原则。确定参与特定信号事件的蛋白质的作用和贡献有助于理解细胞的分子连接。此外，确定信号转导网络的逻辑有助于合理设计具有独特表型行为的细胞。