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

The processes controlling when and where a gene is turned on are complex. Abnormal changes in gene regulation can lead to such diseases as cancer, asthma, and obesity, and as such it is important to medical research that we be able to clearly define the regions of DNA that participate in regulating a gene in order to accelerate development of treatments. Such understanding is important to stem cell research, where again, targeted changes in gene regulation are key to the development of regenerative therapies. One class of proteins involved in gene regulation are transcription factors (TFs), which recognize and bind to short, variable sequences of DNA, and either act to increase or decrease the expression of a nearby gene. For my doctoral research in bioinformatics (a multidisciplinary field uniting computational, statistical and biological sciences) I am developing a predictive algorithm for detecting where TFs bind in DNA sequences. Current algorithms, searching only for short DNA patterns, have limited success. My algorithm incorporates biophysical parameters (e.g. how TFs physically search DNA for a binding site, and interact with other TFs), better reflecting the biochemical process of gene regulation, and improving predictive power. In the second phase of my studies, I will evaluate a hypothesis about how two classes of TFs interact to turn genes on or off when cells differentiate. I will assess how well experimentally known binding locations of each TF class are preserved over evolutionary time, and whether there is a spatial relationship in the DNA between the binding locations. In the final phase I will compare the genetic influence of the two classes. The insights from this proposed research contribute to the understanding of gene regulation, thus potentially impacting future work in regenerative medicine.