A fantastic experience during an undergraduate research project with Dr. George Owttrim led me to a pursuing an M.Sc. degree with Dr. Tracy Raivio where I worked with enteropathogenic E. coli (EPEC), a major source of infant diarrhea in the developing world. My project focused on how the pathogen sensed its host environment in order to activate an appropriate complement of virulence genes. I generated a broad host range, low copy number reporter vector and a series of transcriptional reporters that proved useful for analyzing temporal expression of virulence genes (MacRitchie et al., 2008). Additionally, I conceived a method to make EPEC amenable to classic bacterial genetics techniques improving transformation efficiency 10,000-fold (Hobson et al., 2008).
During my Ph.D. in Dr. Simon Boulton’s lab, I focused on DNA repair, and discovered the beauty of using model genetic systems to ask basic biomedical questions in the context of a whole animal or intact tissue. The primary finding of my dissertation was that the single C. elegans Rad51 paralog, RFS-1, is not a general homologous recombination factor, but rather promotes repair specifically at lesions that block replication forks (Ward et al., 2007). Building on this work, in collaboration with Federica Marini’s group (University of Milano), we found that RFS-1 works with the helicase HELQ-1 to disassemble homologous recombination intermediates in meiosis (Ward et al., 2010). I collaborated extensively both within the lab and with labs at outside institutions to explore the mechanisms of repair of other types of DNA lesions: those that arise from exogenous genotoxic agents and from endogenous sources such as replication stress and meiotic DNA double-strand breaks (Adamo et al., 2008 and 2010; Youds et al., 2008 and 2010; Collis et al., 2006 and 2007; Barber et al., 2008; Goodyer et al., 2008; O’Neil et al., 2013). Through these studies, I realized the power of collaboration in making rapid progress in research, and the overwhelming potential of using a genetic model system to gain insight into human biology.