Chemical Approaches for Interrogating Fundamental Biomedical Processes

项目摘要 细胞通讯涉及小分子信号种类以及无数的 酶活性在空间和时间上都受到严格调控，以协调生物反应。的 这些途径的故障导致异常的细胞功能和人类疾病。我们的长期目标是 发展一个详细的，分子水平的理解细胞信号在正常和疾病状态。 我们通过设计荧光团和蛋白质的开发和应用来解决这个问题， 基于系统。我们的实验室已经开发出新型荧光探针，用于监测和响应 与人类疾病相关的信号物质的存在。在补充工作中，我们开发了 基于蛋白质的方法，用于精确控制细胞信号传导事件。在未来五年内，我们将 应用我们的技术来阐明细胞信号传导的空间方面以及分子的精细细节， 参与细胞信号传导的组件。我们还将寻求新的平台， 用于监测活细胞中的信号传导酶活性的活系统和方法。这项工作将 提供与人类疾病相关的细胞过程的更详细的理解。

Project Summary Cellular communication involves the interplay of small molecule signaling species as well as a myriad of enzymatic activities that are tightly regulated in both space and time to orchestrate biological responses. The malfunction of these pathways results in abnormal cellular function and human disease. Our long-term goal is to develop a detailed, molecular level understanding of cellular signaling in both normal and diseased states. We approach this problem through the development and application of designer fluorophore- and protein- based systems. Our lab has developed new classes of fluorescent probes for monitoring and responding to the presence of signaling species associated with human disease. In complementary work, we have developed protein-based approaches for precisely controlling cellular signaling events. During the next five years, we will apply our technologies to illuminate spatial aspects of cell signaling as well as the fine details of the molecular assemblies involved in cell signaling. We will also pursue new platforms for the gated release of agents in living systems and approaches for monitoring signaling enzyme activity in living cells. Together, this work will provide a more detailed understanding of cellular processes associated with human disease.