Minimally Disruptive Optical Interrogation of Intracellular Signaling

该计划将开发一种破坏性最小的方法，用于使用光来控制活细胞中的酶。他们将选择在糖尿病，肥胖和癌症中具有重要意义的酶，以解决目前的知识空白。他们将为在STEM中代表性不足的高中生开发暑期生物技术培训计划，他们将协助建立生物光子学教学和研究的核心设施，生成生物化学工程和合成生物学的公共教育资源，并为高中生和本科生创造研究机会。蛋白质-蛋白质嵌合体的设计）能够光学控制磷酸化调节酶（即，蛋白酪氨酸磷酸酶和蛋白酪氨酸激酶），而不干扰它们的天然定位和相互作用模式，和（ii）一组由蓝光、红光和红外光调制的光可转换酶。他们将为研究糖尿病、肥胖症和癌症相关信号网络的作用提供一套特定的工具，并开发一种分析空间上不同的磷酸化事件对细胞功能和功能障碍的贡献的通用方法。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

This program will develop a minimally disruptive approach for using light to control enzymes in living cells. They will pick enzymes of importance in diabetes, obesity, and cancer to address current gaps in knowledge. They will develop a summer biotechnology training program for high school students underrepresented in STEM, They will assist with the establishment of a core facility for teaching and research in biophotonics, generate publicly accessible educational resources in biochemical engineering and synthetic biology, and create research opportunities for high school students and undergraduates.They will develop (i) protein architectures (i.e., designs for protein-protein chimeras) that enable optical control of phosphorylation-regulating enzymes (i.e., protein tyrosine phosphatases and protein tyrosine kinases) without interfering with their native patterns of localization and interaction, and (ii) a set photo-switchable enzymes modulated by blue, red, and infrared light. They will supply a specific set of tools for studying the role of signaling networks associated with diabetes, obesity, and cancer, and develop a general approach for analyzing the contribution of spatially distinct phosphorylation events to cellular function and dysfunction.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.