CAREER: Electrically Encoded Innate Immune Sensing in Cardiomyocytes

The ability of cells to detect viral infection and cell damage is essential for the body’s first-line immune defense and for protecting human health. Foreign or misplaced genetic material, such as viral DNA or RNA or a cell’s own nucleic acids appearing in the wrong part of a cell, serves as an important danger signal that alerts cells to these threats. This project asks a fundamental question: can electrically active cells, such as heart cells, use electrical signals to detect and respond to such danger signals? To address this question, the project will study how misplaced DNA and RNA inside heart cells alter cellular electrical activity and influence immune defense. The work is expected to reveal a new link among infection, inflammation, and abnormal heart electrical activity, promoting the progress of science and advancing human health. The project also includes an educational program that engages high school and undergraduate students in hands-on STEM training through the design of affordable laboratory tools, open-source resources, and practical solutions that address real research needs and benefit the broader research community. This project will test the hypothesis that cytosolic nucleic acids can alter the electrical activity of cardiomyocytes by modulating ion channels or their regulatory proteins, and that these electrical changes, in turn, influence innate immune responses. The research will combine patch-clamp electrophysiology, calcium imaging, molecular biology, biochemistry, and computational structural analysis to (1) determine how different cytosolic nucleic acids affect action potentials and intracellular calcium dynamics; (2) identify the ion channels and molecular mechanisms responsible for these effects; and (3) evaluate how changes in electrical activity regulate innate immune signaling pathways. By integrating electrophysiology with innate immune biology, this work aims to establish a new framework for understanding how bioelectric signals participate in innate immune defense. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2541292 | Program: 01003031DB NSF RESEARCH & RELATED ACTIVIT,01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Ang Guo | Institution: North Dakota State University Fargo, FARGO, ND | Award Amount: $570,477 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2541292 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2541292.html