Network precision of chemical and thermodynamic sensing - cells integrate many types of information, including chemicals in the extracellular environment and available energy

The National Institute of General Medical Sciences awarded Vanderbilt University $277,370 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to support research on cellular sensing and signal integration.

The research program comprises three interconnected projects examining how cells perceive and integrate distinct types of biological information. Project 1 investigates crosstalk and synergy between canonical signaling pathways, identifying the molecular basis for arrestin-dependent receptor colocalization at network hubs and downstream effector kinase activation. Project 2 explores thermodynamic signaling driven by succinate and hypoxia-inducible factor, focusing on succinate dehydrogenase activity and succinate release mechanisms. Project 3 evaluates the succinate-sensing receptor SUCNR1 in host-microbiome interactions, examining how succinate localization distinguishes between commensal and pathogenic organisms. The work aims to identify previously unrecognized regulatory nodes that integrate bioenergetics and thermodynamics, with direct implications for therapeutic targeting of cell fate in disease states.

Vanderbilt University's Sponsored Programs Administration serves as the recipient, with performance occurring in Nashville, Tennessee. The award period extends from September 1, 2026, through August 31, 2031. The assistance type is a Project Grant.

Cells must also be able to distinguish self from non-self and further divide non-self into commensals and pathogens. How these distinct pathways coalesce remains poorly understood. This research program explores how cells perceive distinct types of information through three interconnected projects. Project 1 examines crosstalk points and synergy between canonical signaling pathways. We identify the molecular basis for arrestin-dependent receptor colocalization at network hubs and how this activates effector kinases. Project 2 explores thermodynamic signaling driven by succinate and hypoxia-inducible factor (HIF). We identify the molecular basis for succinate dehydrogenase (SDH) activity and succinate release, both of which control this process. Project 3 investigates the succinate axis as relates to host-microbiome interactions. We evaluate the receptor SUCNR1 as a sensor for extracellular succinate and explore how succinate location distinguishes between commensals and pathogens. By dissecting these processes, our work uncovers previously unrecognized regulatory nodes in cells. The specific integration of bioenergetics and thermodynamics provides a broader view of questions of cell fate. Together, these projects reveal interconnected mechanisms with direct implications for therapeutic targeting of cell fate in disease states.