Matthieu G. Gagnon, PhD

The fast up rise of drug-resistant pathogens and the threat that it poses to humanity warrant the pressing need to bring to the market new and improved compounds that target the bacterial ribosome. Over the past fifteen years, high-resolution structures of the ribosome have been determined at several points along the translation pathway, providing insights into decoding, translocation, termination, and the mechanisms by which many antibiotics inhibit protein synthesis. We are interested in understanding the mechanisms of protein synthesis and the basic cellular processes regulating translation by elucidating atomic structures of ribosome, RNA and protein functional complexes.

One of the ongoing projects in our laboratory focuses on the molecular mechanisms by which bacterial pathogens gain resistance to ribosome-targeting antibiotics. Of particular interest are the ribosome rescue factors that bind antibiotic-stalled ribosomes and allow pathogenic bacteria to resume protein synthesis and thrive in the presence of drugs. We seek to obtain tri-dimensional complex structures of the ribosome bound to specialized rescue factors, which will extend our current understanding of the molecular mechanisms that contribute to antibiotic resistance against ribosome-targeting antibiotics in many human pathogens. The availability of high-resolution structures is expected to assist in the design of smarter drugs capable of fighting antibiotic resistance. To achieve these goals, we are using an integrated approach combining biochemical, biophysical, genomic, molecular genetics and structure determination techniques.