Optical Imaging Tools for Elucidating the Roles of Anions and Anionic Modifications in Cellular Signaling

项目摘要 已知阳离子通量驱动细胞信号传导事件，而阴离子被认为起作用， 来中和这些变化。但负离子可能是动态细胞信号吗？这种范式转变 这个问题，在很大程度上，从化学生物学/生物无机的角度被忽视了，尽管事实上， 阴离子失调与包括慢性疼痛、孤独症和癌症在内的多种疾病有关。的 我们研究计划的长期目标是确定细胞来源，蛋白质靶点和信号作用， 在健康和疾病方面，生物相关的负离子，但这样做的技术仍然不发达。本 最后，在这里，我们建议创建新的光学成像工具，将允许建立一个分子水平的图片， 如何，何时，何地，以及为什么负离子实际上在生命系统中起作用。我们的发现不仅 为阴离子在细胞信号传导中的作用提供了基本的理解，而且在表现形式中， 相关疾病状态的诊断和治疗。

PROJECT SUMMARY Cation fluxes are known to drive cellular signaling events, whereas anions are considered to function as counterions to neutralize these changes. But could anions be dynamic cellular signals? This paradigm shifting question, in large part, has been overlooked from the chemical biology/bioinorganic perspective, despite the fact that anion dysregulation is implicated in a variety of diseases including chronic pain, autism, and cancer. The long-term goal of our research program is to identify the cellular sources, protein targets, and signaling roles of biologically relevant anions in health and disease, but the technologies to do so are still underdeveloped. To this end, here we propose to create new optical imaging tools that will allows to build a molecular level picture into the how, when, where, and why of what anions are actually doing in living systems. Our findings, will not only provide a fundamental understanding for the role of anions in cell signaling, but also in the manifestation, diagnosis, and treatment of associated diseased states.