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

活细胞通过溶质载体和离子通道在脂质膜上移动盐、氨基酸和葡萄糖。植物和动物从具有特定载体和通道的细胞中创造组织，以维持渗透平衡，以及将营养物质移进/移出生物体。这些过程会受到环境因素(例如：病原体，有毒刺激物，营养可利用性)。尽管这些反应无处不在，但在大多数系统中，这些刺激调节载体和通道的机制仍未得到解决。因此，我的项目的长期目标是对环境刺激调节载体和渠道的机制进行比较理解。在此背景下，在该发现基金的五年期限内，将进行一个中期目标，即确定猪特异性病原体水痢短螺旋体及其引起腹泻的结肠离子运输的改变的细胞机制。更特别的是，我们将评估腹泻如何随着溶质载体和离子通道的变化而随时间发展。此外，我们还将研究细菌中一种蛋白质的结构和功能，这种蛋白质可能会随着时间的推移导致一些变化。最后，我们将深入研究细胞内细菌诱导的细胞信号事件，这可能导致所见的变化。总的来说，这将有助于该项目的长期目标，寻找在暴露于各种动植物载体和离子通道系统的环境效应物时，激活/不作为，运输和表达的途径/激酶机制的相似性。但是，在短期内，这项工作将深入了解猪结肠上皮运输的调节，但也将确定细胞和生物物理机制，通过这种机制，困扰养猪业100年的细菌可以引起疾病。此外，该项目将在生理学、生物化学和细胞生物学方面培养独特的多名高素质人才（HQP），这些人才是制药行业雇主非常需要和追求的技能。但是，对于加拿大来说，需要对细菌如何引起腹泻（病原体的蛋白质和宿主的细胞反应）有一个更完整的基本了解，这样我们才能用新知识来生产新的治疗方法和根除策略。这将对加拿大的养猪生产者产生重大的经济影响，使他们能够更好地在全球市场上竞争。

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.