Advancing a comparative understanding of the molecular regulation of solute carriers and channels

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A living cell moves salts, amino acids and glucose across its lipid membranes through solute carriers and ion channels. Plants and animals create tissues from cells with specific carriers and channels to maintain osmotic balance, as well as move nutrients into/waste out of the organism. These processes can be greatly altered by environmental factors (eg. pathogens, toxic irritants, nutrient availability). Despite the ubiquitous nature of these responses, the mechanism by which carriers and channels are regulated by such stimulus remains unresolved in most systems. Thus, the long-term goal of my program is to develop a comparative understanding of the mechanisms by which carriers and channels are regulated by environmental stimulus. In this context, during the five-year term of this Discovery Grant, a medium-term goal of defining the cellular mechanisms underlying the pig specific pathogen Brachyspira hyodysenteriae and its alterations of colonic ion transport to cause diarrhea will be undertaken. More specially, we will assess how the diarrhea develops over time with changes in solute carriers and ion channels. In addition, we will also look at structure and function of a protein from the bacteria that may cause some of the changes seen over time. Finally, we will take an in-depth look into the cell signalling events induced by the bacteria within the cell that may contribute to the changes seen. Overall, this will contribute to the longer-term goal of the program, looking for similarities in pathways/kinases mechanisms of activation/inaction, trafficking and expression during exposure to environmental effectors across various animal and plant carrier and ion channel systems. But, in the short-term the work will give insight into the regulation of the pig's colonic epithelial transport, but also define cellular and biophysical mechanisms by which a bacterium that has plagued the swine industry for 100 years can cause disease. In addition, this project will yield unique cross disciplinary training of multiple highly qualified personnel (HQP) in physiology, biochemistry and cell biology, skills which are highly desirable and sought after by pharmaceutical industry employers. But, for Canada, a more complete basic understanding of how the bacterium causes diarrhea (agent's proteins and host's cellular response) is needed to allow us to move forward armed with new knowledge to produce new treatments and eradication strategies. This would have a significant economic impact for swine producers in Canada, allowing them to better compete in a global market.