Grant: Discovery Grants Program - Individual

The overarching goal of my research program is to understand how fishes and other aquatic vertebrates regulate their salt (ions) and pH levels, which are vital for survival. In order to understand the mechanisms at play down to the molecular level or the ion transport proteins, my research integrates whole-animal approaches with molecular-genetic, biochemical and cellular techniques. The development of antibodies to probe the expression of ion transport proteins provides the backbone of my research, which I plan to extend by incorporating novel gene editing techniques (CRISPR-cas9 `knockouts') to learn more about the underlying mechanisms. In the next five years, my research will explore the functional roles of the hydrogen-potassium ATPase (HKA), which is also the ion transport protein responsible for stomach acidification. Stomach acidification by HKA is highly conserved in vertebrates (sharks to humans) and increases the efficiency of protein and phosphorus digestion that are essential to growth and skeletal development. Despite the importance of the stomach, we are presented with the paradox of stomach loss, which has occurred independently multiple times in vertebrate evolutionary history. Our recent examination of three groups of fishes, out of 17 where stomach loss has been reported, indicates that loss of the stomach is accompanied by loss of the genes responsible for stomach digestion. The causes of stomach loss are many, and not well understood, but are likely related to the role of HKA in stomach acidification. In addition, the HKA has multiple variants (paralogues) with sites of expression outside the stomach that are involved in ion (potassium) and pH regulation. In fishes, the gills are an example of an important organ in ion and pH regulation. Regulation of body potassium is also essential for the proper functioning of nerves and muscles, where small changes can have dramatically adverse effects. The proposed research program aims to address: (1) the costs of stomach acidification; (2) the potential causes and (3) consequences of loss of stomach acidification; (4) the relationship between the loss of the stomach genes and the stomach; and (5) the roles that the different variants of HKA play in ion and pH regulation in different groups of animals. These projects will build upon established international collaborations and create new ones, improving Canada's research profile. In addition, the program has a strong training component for young scientists providing high-level research skills, which will facilitate their integration into Canada's research community and industries. In addition to improving our understanding of the role of gene loss in evolution, the program has obvious practical implications to Canada's aquaculture industry where a better understanding of the stomach's role in digestion can lead to improvements in feed formulations to increase growth and production, while reducing waste and pollution.