Cellular Decision Making

 描述(申请人提供)：我的实验室对信令网络如何产生复杂的细胞行为，如极性和运动性，非常感兴趣。要了解这些复杂网络的工作原理，需要工具来隔离和询问信令级联中的各个步骤。我们投入了大量的精力来开发新型的光遗传工具，使我们能够以一种快速、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作。最初，我们开发了这些工具来了解中性粒细胞趋化过程中极性和运动性的调节。我们特别感兴趣的是感官适应的分子基础，它解释了显着的趋化性动态范围，以及细胞如何将外部激动剂中的小不对称转化为肌动蛋白组装中的大不对称，以实现有效的定向运动。最近，我们扩展了我们的光遗传学工具包，以探索其他信号网络，例如T细胞如何区分化学上相似的配体，并承诺要么全有要么全不激活。我们继续开发这项技术，将更广泛的信号和系统置于光遗传控制之下，例如我们对斑马鱼发育过程中图案形成的分析。

 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.