Cellular Decision Making

 描述（由申请人提供）：我的实验室对信号网络如何产生复杂的细胞行为（如极性和运动性）广泛感兴趣。了解这些复杂网络的功能需要工具来隔离和询问信号级联中的各个步骤。我们已经投入了大量的努力来开发新的光遗传学工具，使我们能够以快速、可逆、可滴定的方式激活或抑制细胞内信号，并且可以在空间和时间上进行操纵。最初，我们开发这些工具来了解中性粒细胞趋化过程中极性和运动的调节。我们特别感兴趣的感觉适应的分子基础，占显着的动态范围的趋化性和细胞如何转换小的不对称性，在外部激动剂大的不对称性，在肌动蛋白组装有效的定向运动。最近，我们扩展了我们的光遗传学工具包来探测其他信号网络，例如T细胞如何区分化学相似的配体并进行全或无激活。我们继续开发技术，将更广泛的信号和系统置于光遗传学控制之下，例如我们对斑马鱼发育过程中模式形成的分析。

 DESCRIPTION (provided by applicant): My lab is broadly interested in how signaling networks generate complex cell behaviors such as polarity and motility. Understanding how these complex networks function requires tools to isolate and interrogate individual steps in the signaling cascade. We have invested significant effort developing novel optogenetic tools that enable us to activate or inhibit intracellular signals in a manner that is rapid, reversible, titratable, and can be manipulated in space and time. Initially we developed these tools to understand the regulation of polarity and motility during neutrophil chemotaxis. We are particularly interested in the molecular basis of the sensory adaptation that accounts for the remarkable dynamic range of chemotaxis and how cells convert small asymmetries in external agonist to large asymmetries in actin assembly for efficient directional movement. More recently, we have expanded our optogenetic toolkit to probe other signaling networks, such as how T cells discriminate between chemically similar ligands and commit to all-or-none activation. We continue to develop the technology to bring a wider range of signals and systems under optogenetic control, such as our analysis of pattern formation during zebrafish development.