Grant: Master's Award: Canada Graduate Scholarships

A complete nervous system lies within the wall of the intestine and controls all aspects of digestion, such as contraction and relaxation of the muscle wall, secretion of digestive enzymes and fluids, etc. This is the enteric nervous system, or ENS. However, the intestine is susceptible to inflammation from many different causes, such as infectious bacteria (eg, E coli). This causes changes to the intestinal cells, but the ENS usually adapts to maintain normal control. However, we have shown that severe inflammation can kill some of the neurons of the ENS, and the survivors then have to take over their roles. Understanding the events of the normal response and those of the severe outcomes is important to understand how to keep the ENS alive and functioning well, since this is critical for human health. My research looks at a particular molecule made by the muscle cells of the intestine, which we have found to be important in keeping the ENS neurons alive and functioning. This is GDNF, which is well known for its important role in embryonic development of the intestine, but is not well understood in the adult normal or inflamed intestine. I want to see how the smooth muscle cells make GDNF normally, and how this changes during inflammation. This will use cells taken from the intestine of young rats and maintained in the lab, in tissue culture. This will allow me to look at the size and nature of GDNF as it is made by the muscle cells and acts on the neurons of the ENS, both in normal conditions and in conditions that mimic inflammation. This important since we think that cells initially make a large form of GDNF that has to be reduced in size to become the effective form, and we want to know how this occurs normally, and how it changes during inflammation. I have two goals, which is to show that some of specific factors that cause inflammation also cause the muscle cells to make more GDNF as well as the enzyme that creates the final critical effective molecule. These events would keep neurons alive and promote their ability to control other intestinal cells. Although I have just started my graduate research, I found initial results which support these outcomes. I am excited to continue to understand how some aspects of inflammation are actually beneficial, in this case through helping to keep intestinal neurons alive. Understanding this is important because it should allow us to find new ways to prevent damage to the ENS, and so keep the intestine functioning normally. This is particularly important in IBD (Inflammatory Bowel Disease; eg, Crohn’s disease), which characteristically causes repeated, severe intestinal inflammation. IBD is currently incurable and affects many Canadians, with a high impact on quality of life and medical costs. New understanding of the processes in IBD will lead to new therapies, and ultimately new approaches to disease treatment.