Minimally Disruptive Optical Interrogation of Intracellular Signaling

该计划将开发一种最小干扰的方法，利用光来控制活细胞中的酶。他们将选择对糖尿病、肥胖症和癌症具有重要作用的酶，以解决目前的知识差距。他们将为在STEM中代表性不足的高中生开发一个夏季生物技术培训计划，他们将帮助建立生物光子学教学和研究的核心设施，产生可公开访问的生化工程和合成生物学的教育资源，并为高中生和本科生创造研究机会。他们将开发(I)蛋白质结构(即蛋白质-蛋白质嵌合体的设计)，使其能够在不干扰其固有的定位和相互作用模式的情况下对磷酸化调节酶(即蛋白质酪氨酸磷酸酶和蛋白质酪氨酸激酶)进行光学控制，以及(Ii)一套受蓝光、红光和红外光调制的可光开关酶。他们将提供一套具体的工具来研究与糖尿病、肥胖和癌症相关的信号网络的作用，并开发一种通用的方法来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。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.