Friday, April 11, 2025
4/11/2025
Fluorescent Biosensors to Illuminate Chloride Homeostasis and Signaling - PROJECT SUMMARY Chloride is the most abundant inorganic anion in the human body. It is required for essential physiological functions ranging from electrolyte balance, acidosis, innate immunity, circadian rhythms, and even taste sensation. However, disruptions in chloride homeostasis, arising from diet or genetics, are linked to diseases including cystic fibrosis, hearing loss, kidney stones, myotonia, and osteopetrosis, as well as cancers, cardiac dysfunction, and neurological disorders. To dissect the contributions of chloride in healthy and disease states, a fundamental understanding of its distribution, regulation, and biomolecular targets at the cellular level is needed. As a step towards this long-term goal, the proposed research program will engineer and apply new fluorescent protein-based imaging technologies to monitor and measure chloride in living systems across time and space dimensions. Over three independent project directions, innovative strategies will be used to address practical gaps in biosensor design, while at the same time rigorous and reproducible biological applications will be established in user-friendly cell lines to democratize chloride imaging. Ultimately, the resulting technologies will illuminate chloride in fundamental biological processes that are dysregulated in disease, leading the way to therapeutically target this vital anion for improving human health.
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