Engineering a new class of optogenetic tools targeting small GTPases and kinases

描述（由申请人提供）：我们的思维过程依赖于称为神经元的神经细胞网络。 这些网络必须在发育过程中正确形成，神经元必须能够正确地相互沟通，以便我们的大脑正常运作。 当神经系统疾病发生时，它们通常可以追溯到神经元内的一种或一组信号蛋白无法发挥作用。 如果仅限于使用传统的生物化学和遗传学方法，了解这些蛋白质应该如何工作并不是一件容易的事情，因为这些蛋白质通常在细胞内的不同时间和位置发挥不同的作用。 要确定这些蛋白质的功能如何取决于其活动的位置和时间，一个强有力的方法是使研究人员能够在完整神经回路细胞内的精确时间或位置打开或关闭它们。 目前的提议旨在产生一套工具，可以通过光脉冲打开或关闭生命系统中的蛋白质。 通过这些工具获得的知识可以使我们更接近治愈许多神经系统疾病。

DESCRIPTION (provided by applicant): Our thought processes rely on networks of nerve cells called neurons. These networks must be properly formed during development and the neurons must be able to communicate correctly with each other for our brains to function normally. When neurological disorders occur, they can often be traced back to how one or a group of signaling proteins within neurons failed to perform. To understand how these proteins should have worked is not an easy task if one is limited to using traditional biochemical and genetic approaches, because the proteins often carry out different roles at different times and locations inside the cells. One powerful way to identify how the functions of these proteins depends on the location and timing of their activity would be to enable investigators to switch them on or off at precise times or locations inside the cells of intact neural circuits. The current proposal aims to generate a set of tools that can switch proteins on or off in living systems with a pulse of light. Knowledge gained with these tools can lead us one step closer to curing many neurological disorders.