Collaborative Research: Role of endogenous carbon monoxide (CO) in hypoxia tolerant species

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Often, carbon monoxide (CO) is thought of as a strictly toxic gas, but CO is also naturally produced in the body from the breakdown of heme, a key component of the primary oxygen-carrying protein (hemoglobin) found in red blood cells. Members of the research team recently discovered that certain species of deep-diving seals have moderately high concentrations of CO in their blood (similar to those measured in heavy cigarette smokers). Currently, these are the only species known to naturally produce such high levels of CO, which may elicit strong protective effects on tissues that experience low oxygen or reduced blood flow, as regularly occurs during diving. This project tests the hypothesis that deep-diving seals produce higher concentrations of CO as a potential adaptive mechanism to avoid injuries associated with their extreme diving behaviors. It will investigate the source of the high CO levels in the blood, how the production of CO is regulated, and the range of CO concentrations in blood and tissues from several species of air-breathing divers. Species shown to produce high concentrations of CO will be further examined to evaluate the potential protective properties associated with the gas. The research has potential applications that could assist in minimizing human reperfusion injuries (e.g., as a result of a stroke). The project is highly collaborative and includes three Early-Career Investigators, two female scientists, one post-doctoral researcher, and several graduate and undergraduate students. Several public education and outreach activities are planned, including contributions to public education at Ano Nuevo State Reserve in California.The impact of endogenously produced gas molecules on the regulation of physiological processes is a rapidly expanding area of biological research. However, the interactions between these molecules and their biological targets, and the adaptive roles they play in wildlife, are currently unknown. This project investigates the genetic and physiological mechanisms driving CO production and the potential for the gas to elicit cytoprotective effects during hypoxia and/or ischemia in diving mammals. The project tests the hypothesis that higher CO concentrations result from elevated heme-protein stores and a high turnover rate of these stores via short erythrocyte lifespans. It will also test whether CO has beneficial effects in diving species, including cytoprotection, increased hemoglobin-oxygen affinity, and altered mitochondrial function. The results from this study will advance understanding of physiological adaptations for hypoxia tolerance (e.g., in diving, high-altitude, or burrowing species). This collaborative project supports three Early-Career Investigators and promotes research training and education for one post-doctoral researcher, four graduate students, and over 20 undergraduates across six institutions. Results from this study will be incorporated into courses taught by the investigators. Broader Impacts of the project include participation of underrepresented minority groups, enhanced infrastructure for research and education at six institutions, and broad dissemination of research and educational materials to enhance public understanding of key scientific concepts.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.