Grant: Discovery Grants Program - Individual

The long-term goal of my research program is to understand the mechanisms regulating cardiac function and metabolism in aquatic animals. The heart is a limiting factor for anaerobic stress survival, but the mechanisms constraining maximum cardiac function are unresolved. In fish, anaerobic stressors impair gill osmoregulation and increase tissue osmotic strength. Regulatory volume increase (RVI) and decrease (RVD) mechanisms protect heart cell volume via the movement of ions and osmolytes, with taurine being the most important, but the implications of RVI and RVD for heart function are poorly understood. In theme 1, we will determine if changes in tissue osmotic strength drive taurine and ion efflux associated with RVD. Osmolality will be measured in hearts from taurine replete and deficient fish exposed to stress and relationships developed to estimate the magnitude of heart RVD in vivo. Proteomics will identify proteins regulated by taurine, and we will then assess their post translational regulation and contribution to contractile function. The role of RVD mechanisms in protecting intracellular pH (pHi) under stress will be characterized. Animals will be rendered taurine deficient and pharmacological methods will be used to determine how inhibiting taurine flux contributes to pHi regulation. In theme 2, we aim to understand how mechanisms buffering changes in osmolality regulate heart function and metabolism. In abalone, a mollusc, tauropine dehydrogenase (TDH) condenses pyruvate with taurine to form tauropine and buffer increases in osmolality under hypoxia. This depletes free taurine, which is a potent cardiac regulator in molluscs. Relationships between heart function, tissue osmolality, metabolism, and taurine flux will be characterized in abalone. We will finally focus on the novel metabolite lactate-phenylalanine (Lac-Phe), which buffers extracellular osmolality under anaerobic stress while simultaneously regulating energy metabolism. We will characterize relationships between Lac-Phe production and osmolality in fish that do and do not accumulate lactate under hypoxia, identify and measure the expression of the Lac-Phe receptor, its downstream targets, and key regulators of energy homeostasis. Theme 1 will improve our understanding of interactions between intracellular osmolality and cardiac function and Theme 2 will help us understand how extracellular osmotic buffers influence cardiac function and energy homeostasis. This will allow us to better predict the impacts of climate change on aquatic animals. The research program will train at least 22 undergraduate and 5 graduate students, emphasizing scientific skill development and employing impactful equity, diversity, inclusion, and accessibility strategies relevant to our primarily undergraduate institution. The proposed research leverages unique model systems and a combination of physiological, molecular, and biochemical techniques to address this fundamental gap in knowledge.