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

Research in our lab is centered around understanding processes that mutate our own DNA, or the DNA of viruses after they infect cells. All biological organisms have multiple complex and redundant cellular pathways that vigilantly monitor and maintain their genomic integrity. In other words, since the DNA sequence of an organism is its very definition, protecting the fidelity of this sequence is of paramount importance. As a general rule, the more complex an organism, the more pathways it has developed to ensure faithful maintenance and replication of its DNA. The sole exception to this rule occurs in specialized cells of the immune system amongst jawed vertebrates. These white blood cells known as lymphocytes actually damage their own DNA on purpose. They have developed mechanisms that mutate their DNA sequence and also physically break their chromosomes, in order to change the sequence of- or rearrange the location of specific genes involved in an immune response. In so doing, they are able to adapt during an immune response and become more effective fighters against bacteria, viruses, parasites and toxins. On the other hand, these same DNA-mutating processes used for the good of the immune system may be targeted to the wrong genes in the lymphocytes and cause mutations and chromosomal breaks in oncogenes that can lead to the transformation of normal lymphocytes into cancers known as lymphoma or leukemias. Similarly, several of these DNA-mutating processes are used by cells of our immune system to combat invading viruses. However, recent evidence shows that viruses can adapt and use these "defense" mechanisms to further mutate their own genomes to be able to escape from drug treatment and immune recognition. I will be investigating the molecular mechanisms of these processes, in particular how they are linked to cancer and anti-viral responses.