Emily Gesner Department of Biochemistry Supervisor: Dr. Andrew MacMillan Originally from Fredericton, NB I completed a BSc. (Honours) with a double major in Biology and Chemistry at the University of New Brunswick, Fredericton. At UNB I began my scientific career through a Federal Student Work Exchange Program (FSWEP) position with Agriculture and Agri-Food Canada at the Potato Research Centre in Fredericton. I worked for three summers analyzing nitrogen levels in soil, plant, and leaf samples in various crop yield studies and collecting plant, soil, and green house gas samples from potato, wheat and barley fields testing the effect of fertilizer composition on plant yield. I truly enjoyed this on hands on experience with science which lead me to pursue my PhD at the University of Alberta. Under the supervision of Dr Andrew MacMillan in the Biochemistry Department, I undertook a number of projects studying small regulatory RNAs in a variety of species including Drosophila, C. elegans, Humans, and Bacteria. My experience in the MacMillan laboratory has been an exciting period in my development as a researcher and I have gained invaluable skills relevant to the in vitro analysis of biological systems. In bacteria and archaea, small RNAs derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) genetic loci are involved in an adaptable and heritable gene-silencing pathway which can target viruses, plasmids, and transposons. This system allows bacteria to acquire resistance to viral infection by incorporating short invading DNA sequences into their genome as CRISPR spacer elements separated by short repeat sequences. Processing of long primary transcripts (precrRNAs) containing these repeats by an RNA endonuclease generates the mature effector RNAs that interfere with phage gene expression. The goal of this project was to understand the mechanism and structural details of the Thermus thermophilus CRISPR Cse3 endonuclease which is essential for the processing of the CRISPR transcript into mature effector CRISPR RNAs (crRNAs). High resolution X-ray structures of Cse3 bound to repeat RNAs model both the pre- and post-cleavage complexes associated with crRNA processing. These structures establish the molecular basis of specific CRISPR RNA recognition and suggest the mechanism for generation of effector RNAs responsible for gene-silencing. This project was not accomplished alone and I would like to acknowledge Dr. Matthew Schellenberg, the co-lead author on this paper, for his significant contribution to this work. I would also like to thank the other contributing authors, Erin Garside, Mark George, and my supervisor Dr Andrew MacMillan. I graduated from my PhD program in June, 2010 and am currently employed at Resverlogix Corp., a biotechnology company located in Calgary that develops drugs that reduce heart disease and arthrosclerosis by increasing the levels of HDLc (the "good cholesterol").