I’m a postdoctoral research fellow evaluating the side effects (hearing loss) and antimicrobial activities of aminoglycosides, a life-saving group of antibiotics used worldwide. As part of a cross-disciplinary research team in the Cheng and Ricci Laboratories, my goal is to develop safer aminoglycoside antibiotics for patients with bacterial infections (1). Drug development centers around the concept that by preventing drug entry into cochlear hair cells we can prevent hearing loss. My recent focus has been on determining are the individual components of gentamicin different in terms of their toxicity to the ear and to bacterial pathogens. This work involves collaborating with a team of scientists who perform crystallography, electrophysiology, nuclear magnetic resonance spectroscopy, confocal microscopy, in vivo and in vitro toxicity experiments. As part of this work, I developed higher-throughput drug-screening protocols for ear tissues (2). My previous work in the lab focused on investigating the effects of aminoglycosides on the bacterial ribosome using x-ray and LCLS crystallography. As part of the team, I helped to compare the effects of four drugs on the ribosome. Our studies revealed novel conformational changes at a highly conserved ribosomal region associated with mitochondrial disorders in humans (3) – the region that was a focus of my PhD studies at the UCL Institute of Child Health (4).
1. O’Sullivan ME, Perez A, Lin R, Sajjadi A, Ricci AJ, and Cheng AG. Towards the prevention of aminoglycoside-related hearing loss. Frontiers in Cellular Neuroscience. 2017;11:325.
2. Krey JF, Chatterjee P, Dumont RA, O’Sullivan M, Choi D, Bird JE, et al. Mechanotransduction-dependent control of stereocilia dimensions and row identity in inner hair cells. Current biology : CB. 2019.
3. O’Sullivan ME*, Poitevin F*, Sierra RG*, Gati C*, Dao EH, Rao Y, et al. Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature. Nucleic Acids Res. 2018;46(18):9793-804.
4. O’Sullivan M, Rutland P, Lucas D, Ashton E, Hendricks S, Rahman S, et al. Mitochondrial m.1584A 12S m62A rRNA methylation in families with m.1555A>G associated hearing loss. Hum Mol Genet. 2015;24(4):1036-44.