Matthieu G. Gagnon, PhD
Assistant Professor, Department of Microbiology & Immunology
Tel: (409) 772-2326
Fax: (409) 772-2366
E-mail: magagnon@utmb.edu
Campus Location: 4.104C Medical Research Bldg
Mail Route: 1019
Research
Our research focuses on structural studies of protein synthesis,
ribosome structure and function, ribosome-binding factors, antibiotics,
antibiotic resistance mechanisms, X-ray crystallography, cryo-electron
microscopy.
Current Projects
The increasing occurrence of bacterial resistance to antibiotics
ranks among the greatest threats currently facing human health. The
severity of the situation is such that it is propelling the search for
new and more effective therapeutics. Antibiotics inhibit bacterial
growth by targeting essential cellular processes such as cell wall
synthesis, DNA replication/transcription and protein synthesis. Protein
synthesis is mediated by a large macromolecular machine, called the
ribosome. Nowadays, more than half of clinically relevant antibiotics
cure infections by binding and inhibiting the bacterial ribosome, making
the ribosome a validated drug target in the cell.
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.
We are always looking for highly motivated individuals who are
interested in joining our dynamic and fast growing research group.
Publications