Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Huntington's Disease (HD) is an adult onset brain disorder which is caused by a mutation in the gene that encodes for the protein huntingtin (htt). While there has been considerable research into the role of mutant htt in causing brain cell death, little is known about the normal function of this protein. Understanding the conditions that cause htt to be turned on in the brain is an important step towards discovering the function of both the normal and mutated htt. During its life time a cell will turn on or off certain genes to optimize its survival as its environment changes and the cell ages. Cells use a genetic sequence called a promoter, which lies ahead of a gene, to regulate the expression of genes. Promoters are comprised of sets of genetic sequences that can specify the binding of special proteins called transcription factors (TFs). There are many different types of TFs, some that induce expression and others that prevent it. The combination of TFs at a given promoter regulate how much a gene is expressed, if at all. By regulating the concentrations of different TFs the cell can then control the expression of specific genes. The purpose of the project is to discover and characterize the htt promoter so that we know which TFs are binding to the promoter and how these TFs are affecting htt expression. In order to do this the cellular concentrations of specific TFs will be manipulated and the effect on the htt promoter will be assessed. To assay promoter function the htt promoter will be attached to the same gene that allows fireflies to glow. Thus if the treatment used increases htt promoter activity the cells will glow more than cells without treatment and conversely if the treatment decreases promoter activity the cells will glow less. By knowing which TFs are important for htt expression new drug therapies can be aimed at preventing htt expression which will prevent HD.