Grant: Operating Grant

After eating, food is digested in the gastrointestinal (GI) tract. The process of digestion requires the food to be moved along from the stomach and through the intestines, because absorption of nutrients takes place at various points along the length of the gut. What is left after digestion has to be removed or the system becomes blocked. The movement of digestive contents is very carefully controlled; too fast, and digestion is not complete and nutrients are wasted, too slow, and there is the risk of blockage and excessive growth of bacteria that live in the gut. The control of gut movements is exercised by a rich system of nerves called the enteric nervous system or 2nd brain, because it is so large and complex. Nerves do not work alone. They require support from special cells called glia, which form a network around the nerves. Through my research, we know that nerves communicate with the glial cells by releasing substances called chemical messengers. This nerve-glial communication is important for the system to work effectively. This chemical communication appears to go wrong when the gut is diseased. In fact, some of the symptoms of gut diseases such as inflammatory bowel disease (IBD), may occur because of inadequate communication between nerves and glial cells in the gut. We propose to study one of the most important chemical messengers called ATP that is used in the dialogue between nerves and glial cells. We will study it in normal tissues in order to understand how the healthy gut behaves. Then we will study this chemical messenger (ATP) in animals that have been treated to give them a condition like IBD. We do this in order to understand how the chemical signaling is altered when the gut is diseased. These studies will give us new insights into the chain of events that leads to the development of GI disease. The new knowledge that we gain will also be used to develop better treatments for GI disorders, including IBD.