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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
1R35GM128923-01
Application #
9576133
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Sammak, Paul J
Project Start
2018-08-01
Project End
2023-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Texas-Dallas
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
800188161
City
Richardson
State
TX
Country
United States
Zip Code
75080