Elena Kuzmin, Biochemistry
Identifying co-operating genetic mutations within large chromosomal deletions associated with triple negative breast cancer
Cancer is associated with an accumulation of alterations in genes that enable cancer cells to grow uncontrollably. These alterations contribute to increased deleterious function or loss of function of genes that normally regulate cell growth. It is now recognized that in addition to alterations in single genes, large deletions on chromosomes comprising multiple genes are also important events in cancer. As a Banting fellow, supervised by Prof. Morag Park, my project will focus on a large deletion, frequently found in a subset of breast cancer called triple negative breast cancer (TNBC). This subset has no targeted therapies and has the worst survival. The aim of my project is to use recently developed technology to study which combinations of genes in large chromosomal deletions are important in cancer. Such a systematic identification of genetic interactions within large chromosomal deletions is expected to reveal genetic events that modulate TNBC, enhance our understanding of the disease and offer possible avenues for personalized interventions to individuals diagnosed with TNBC.
Lauralicia Sacre, Biochemistry
Understanding the Nuclease Activity of B. subtilis MutL in DNA mismatch repair
One of the most fascinating aspects of the DNA damage response is how repair proteins find the lesions regardless of context, thereby ensuring the repair of each and every lesion. DNA mismatch repair corrects errors that occur while DNA is being copied and the conserve MutL protein is essential in this pathway.
The Guarne laboratory has made key contributions to the functions of MutL. However, MutL does not look like any other nuclease and, therefore, it is not well understood how it cuts DNA yet. My research focuses in understanding how does the structure-specific nuclease MutL cleaves DNA. Defects in this protein increase the mutation frequency and leads to genetic instability. In fact, deficiency in the MutL gene has been associated with Lynch syndrome. I will use a combination of biochemical, biophysical and structural biology techniques to study how MutL binds and cleaves DNA.