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.

PROJECT NARRATIVE Negatively charged ions (anions) such as chloride and sulfate contribute to a wide range of functions in our bodies, including the way we feel pain and carry out detoxification processes. If we could capture a snapshot of these ions in action, fundamental information about how these ions contribute to human health and disease would be gained, which, in turn, can lead to new treatments for anion-dependent diseases (e.g. cystic fibrosis, autism, chronic pain). To capture this snapshot, we are engineering ‘molecular cameras’ that bind to a target anion in a living cell and emit a burst of light similar to a camera flash.