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

DNA is the carrier of genetic information that is passed from one generation to the next. Inside cells, DNA is highly condensed and chromatin is the first level of DNA compaction that will eventually result in the formation of chromosomes. Changes in chromatin structure can lead to certain cancers, neurodegenerative diseases and inherited childhood syndromes. Understanding chromatin processes is therefore important to develop treatments for these conditions. During the first level of DNA compaction, DNA is condensed into chromatin with the help of DNA-packaging proteins called histones. DNA wraps around eight core histones, two of H2A, H2B, H3 and H4, to assemble into chromatin. One of several ways to modify chromatin is to incorporate histone variants that are slightly different from the core histones. H2A.Z is a variant of H2A that is highly conserved throughout evolution. H2A.Z is found at specific regions on the genome and has roles in proper genome stability and cell growth. H2A and H2A.Z are structurally different toward the end of the protein. My hypothesis is that the difference in function between these two histones also lies in this region. I will use this difference to create mutants of H2A.Z and H2A to determine the differences in the way the two histones are deposited into chromatin. The ultimate goal of this research is to understand how chromosome regions containing H2A.Z are created. This will contribute significantly to the understanding of H2A.Z biology and how this variant is deposited into chromatin. Understanding how these basic chromatin processes work will help in developing new treatments to improve human health.