microRNAs as determinants of metabolic phenotypes in teleost fish

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Bony fishes, the largest vertebrate infraclass, have evolved to inhabit unique ecological niches and exhibit a great variety of metabolic phenotypes. Molecular factors shape organismal metabolic phenotypes in bony fishes across the lifecycle and generations. This research investigates the role of a specific class of molecules called microRNAs (miRNAs) in shaping metabolic phenotypes in adult bony fishes and across their development and generations. miRNAs are short, non-protein coding gene products which decrease mRNA stability and inhibit their translation through complementary base pairing with targeted mRNAs. Now regarded as potent regulators of metabolism in mammals, their comparative role in bony fishes is poorly characterized. Our research will determine the role of miRNAs in two species, rainbow trout and zebrafish, which are well suited to determine the role of miRNAs in unique metabolic phenotypes in adult bony fishes and across development and generations, respectively. Rainbow trout possess a unique metabolic phenotype in that they tolerate sustained fasting and are intolerant to glucose-rich diets. Since the recent publication of the rainbow trout genome, we now dispose of a detailed characterization of miRNAs in this species and bioinformatics tools to predict regulated targets. We will thus use rainbow trout, a well-established model in the comparative physiology of metabolism, to determine regulation and function of miRNAs, including species-specific miRNAs, in its unique metabolic phenotype. To address metabolic roles of miRNAs across development and generations, we will use zebrafish, a developmental model with short generational time. We will determine the role of nutritional metabolic stimuli in early development on adult and trans-generational metabolic phenotypes under baseline conditions or in response to additional metabolic stimuli. The role of miRNAs in the emergence of metabolic phenotypes across these timescales will be determined by determining differential miRNA expression across development and in gametes, and by modulating embryonic expression of identified miRNA candidates. Together, these approaches will provide comparative insight into the role of miRNA molecules in the physiology metabolism in bony fish, which has important implication for aquaculture breeding programs and nutrition, as well as ecotoxicology of cyprinid and salmonid species of concern in the Canadian environment.