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使盐、氨基酸和葡萄糖穿过其脂质膜。植物和动物从具有特定载体和通道的细胞中产生组织，以维持渗透平衡，以及将营养物质移入/移出生物体。这些过程可能会受到环境因素的极大影响（例如，病原体、有毒刺激物、营养物可用性）。尽管这些反应无处不在，但在大多数系统中，载体和通道受这种刺激调节的机制仍然没有得到解决。因此，我的计划的长期目标是发展的载体和渠道的机制，由环境刺激调节的比较理解。在此背景下，在本发现资助的五年期内，将开展一项中期目标，即确定猪特异性病原体猪短螺旋体及其改变结肠离子转运导致腹泻的细胞机制。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着时间的推移而发展。此外，我们还将研究细菌中蛋白质的结构和功能，这些蛋白质可能会导致随着时间的推移而发生的一些变化。最后，我们将深入研究细胞内细菌诱导的细胞信号事件，这些事件可能有助于观察到的变化。总体而言，这将有助于该计划的长期目标，寻找在各种动植物载体和离子通道系统暴露于环境效应物期间激活/不活动，贩运和表达的途径/激酶机制的相似性。但是，在短期内，这项工作将深入了解猪的结肠上皮运输的调节，而且还定义了困扰养猪业100年的细菌引起疾病的细胞和生物物理机制。此外，该项目将产生多个高素质人员（HQP）在生理学，生物化学和细胞生物学，这是非常可取的，并由制药行业雇主追捧的技能独特的跨学科培训。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）有更完整的基本了解，以便我们能够利用新知识向前迈进，从而产生新的治疗方法和根除策略。这将对加拿大的生猪生产商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.