Modulation of P-glycoprotein 170 function as a therapeutic target in ulcerative colitis

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Ulcerative colitis is a common and chronic inflammatory disease affecting the large intestines. The cause of the illness is unknown, although there is strong evidence that both genetic and environmental factors contribute. Current treatment is unsatisfactory, relying on toxic drugs which suppress the immune system. Recently studies from our laboratory suggest that variations in a gene (MDR-1) that codes for a pump that transports foreign particles out of cells might be involved in causing the disease. I plan to study this in detail in this project. I will manipulate the levels of gene and pump levels in mouse models of ulcerative colitis and human gut cells and determine if this influences the level of gut inflammation. I will use the latest gene manipulation technology to change the levels of gene expression and to study gene changes that occurs after PgP manipulation. This will also provide the opportunity to study how PgP interact with other mechanisms of gut defence and the immune system. I will test how PgP respond to fragments of bacteria and chemicals which provoke inflammation. These experiments provide the basis of a possible new mechanism for how UC develops and importantly, the development of a future treatment.