Uncovering new approaches to manipulate and probe biochemical processes with spatial and temporal precision.

虽然成像技术的进步使科学家能够观察细胞现象和 越来越详细的蛋白质复合体，我们扰乱和操纵细胞的能力 同样精细的精确度也落后了。为了更好地了解动态蜂窝环境，工具 可以有选择地实时扰乱生物过程，具有快速、可逆、可调和空间- 需要有选择性的控制。在这一领域向前迈出的重要一步来自蜂窝领域 光遗传学，其中光感觉蛋白被设计成控制各种细胞过程 灯。因为光可以以快速的时间和亚细胞空间精度传递，所以这样的工具 允许史无前例的生物防治。在之前的工作中，我们开发了基于以下条件的新型光遗传工具 植物光感受器隐花色素2(CRY2)，可用于精确操纵蛋白质 互动、本地化和活跃性。虽然这些工具已经成功地调节了蛋白质 光遗传调控的功能、改进和新的策略是必要的。在建议的 工作中，我们将迎来新一轮的光基因工程，改进现有的战略， 将光遗传工具扩展到新的领域，开发新的光接收器模块，并测试新的 工程设计是用光来调节蛋白质的功能。该项目的长期目标是 使用FAST启用一套模块化精密工具，用于探测和操作生化过程 时间控制和从亚细胞到生物体的空间尺度。

While advances in imaging technologies are enabling scientists to observe cellular phenomena and protein complexes in increasingly greater detail, our ability to perturb and manipulate cells with equally fine precision have lagged. To better understand the dynamic cellular environment, tools that can selectively perturb biological processes, in real-time, with fast, reversible, tunable, and spatially- selective control are required. A major step forward in this area has come from the field of cellular optogenetics, wherein photosensory proteins are engineered to control various cellular processes with light. Because light can be delivered with fast temporal and subcellular spatial precision, such tools allow unprecedented biological control. In prior work, we developed novel optogenetic tools based on the plant photoreceptor cryptochrome 2 (CRY2), which can be used to precisely manipulate protein interactions, localization, and activity. While these tools have been successful at regulating protein function, improvements and new strategies for optogenetic regulation are needed. In the proposed work, we will usher in a new wave of optogenetic engineering, improving upon existing strategies, extending optogenetic tools into new areas, developing new photoreceptor modules, and testing novel engineering designs to regulate protein function with light. The long term goals of the project are to enable a set of modular precision tools for probing and manipulating biochemical processes with fast temporal control and over spatial scales ranging from subcellular to organismal.