Grant: Discovery Grants Program - Individual

In vertebrates, homeostatic regulation of oxygen and carbon dioxide is essential for survival. My research program will shed new light on the evolution of chemosensing mechanisms that underlie cardiorespiratory reflexes among the vertebrates, especially during the transition from water-to-air. My proposed research is innovative as it will be at the forefront of comparative studies aimed at elucidating the role of neuroepithelial cells (NECs) as general metabolic sensors. By expanding my studies to include the lamprey (i.e., an early extant vertebrate), teleosts, and amphibious fish, I anticipate that my work will address whether the fundamental mechanisms of chemosensing arose during early vertebrate evolution. The long-term goal of my research program is to determine if gill and/or skin NECs of water-breathers including teleosts, amphibious fish, and early jawless vertebrates (e.g. lamprey) initiate cardiorespiratory reflexes in response to environmental disturbances by acting as polymodal chemoreceptors which sense respiratory gases (i.e., oxygen, carbon dioxide, ammonia and hydrogen sulfide), and tissue metabolites (e.g. lactate) via evolutionary conserved signaling pathways. This goal will be accomplished through the following short-term objectives: (1) Demonstrate how NECs found in respiratory organs of fishes act as general metabolic sensors. (2)Explain how patterns of gill innervation mediate organismal responses to various internal and external chemostimuli. (3)Determine the developmental patterns of chemosensory cells in the skin vs. gills of lamprey. My research program will provide foundational knowledge on the role of fish gill and skin NECs in the evolution of chemosensing mechanisms. Importantly, my proposed studies will expand on my recent demonstration that NECs can also sense lactate; this will provide the first mechanistic understanding at the cellular and subcellular levels of this novel pathway in an aquatic vertebrate. These studies promise to be impactful by providing the first evidence that NECs should be considered as `metabolic sensors' rather than simply sensors of the respiratory gases, changing our current understanding of the role of these cells. Finally, my proposed studies on the lamprey will be the first to test the theory that the fundamental peripheral chemosensing mechanisms, that have been well studied in air-breathing mammals, have their origin in an early extant water-breathing vertebrate. Significantly, the proposed studies will set a solid platform for future studies devoted to an understanding of the plasticity mechanisms that shape adaptive reflex responses to natural stressors experienced by aquatic vertebrates such as chronic or intermittent hypoxia.