Matthieu Gagnon
Matthieu G. Gagnon, Ph.D.Assistant Professor, Department of Microbiology and Immunology


Contact Information:
Phone: (409) 772-2326
Fax: (409) 747-7050

Howard Hughes Medical Institute Post-doctoral Fellowship, 2017, Yale University, New Haven, CT

PhD, 2009, University of Montreal, Montreal, Quebec, Canada

MSc, 2002, University of Montreal, Montreal, Quebec, Canada

BSc, 2000, University of Montreal, Montreal, Quebec, Canada

Research Interests:
Work in the Gagnon laboratory is directed at understanding the structural basis of the functions of proteins and nucleic acids involved in gene expression, particularly translation. In all living cells, translation is mediated by a large macromolecular assembly, the ribosome. We are interested to characterize the mechanisms of regulation of protein synthesis mediated by ribosome-binding proteins, RNAs and small molecules, such as antibiotics. Understanding the mechanisms of protein synthesis in atomic details will lead to new antibiotic targets, which is particularly important nowadays with the increasing occurrence of bacterial resistance to antibiotics being one of the biggest threats to global health. More than half of clinically relevant antibiotics cure infections by inhibiting the bacterial ribosome, making the ribosome a validated drug target in the cell. Many pathogenic bacteria have acquired resistance mechanisms that rely on specialized ribosome-binding proteins capable of rescuing antibiotic-inhibited ribosomes. Rescue of protein synthesis allows pathogens to thrive in the presence of drugs. We are seeking to characterize the molecular mechanisms exploited by many human pathogens to rescue drug-inhibited ribosomes, making them resistant to commonly used antibiotics. To achieve these goals, our laboratory uses an integrated approach combining biochemical, biophysical, genomic, molecular genetics and structure determination techniques.

Selected Publications:

  1. Lin J, Zhou D, Steitz TA, Polikanov YS, Gagnon MG. (2018) Ribosome-targeting antibiotics: Modes of action, mechanisms of resistance, and implications for drug design. Annu. Rev. Biochem. 87: 451–478
  2. Gagnon MG, Lin J, Steitz TA (2016). Elongation factor 4 remodels the A-site tRNA on the ribosome. Proc. Natl. Acad. Sci. U.S.A. 113: 4994–4999
  3. Gagnon MG, Roy RN, Lomakin IB, Florin T, Mankin AS, Steitz TA (2016). Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. Nucleic Acids Res.44: 2439–2450
  4. Roy RN, Lomakin IB, Gagnon MG, Steitz TA (2015). The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nat. Struct. Mol. Biol. 22: 466–469
  5. Lin J, Gagnon MG, Bulkley D, Steitz TA (2015). Conformational changes of elongation factor G on the ribosome during tRNA translocation. Cell 160: 219–227
  6. Gagnon MG, Lin J, Bulkley D, Steitz TA (2014). Crystal structure of elongation factor 4 bound to a clockwise ratcheted ribosome. Science 345: 684–687
  7. Gagnon MG, Seetharaman SV, Bulkley D, Steitz TA (2012). Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome. Science 335: 1370–1372
  8. Gagnon MG, Steinberg SV (2010). The adenosine wedge: A new structural motif in ribosomal RNA. RNA 16: 375–381
  9. Gagnon MG, Boutorine YI, Steinberg SV (2010). Recurrent RNA motifs as probes for studying RNA-protein interactions in the ribosome. Nucleic Acids Res. 38: 3441–3453.
  10. Gagnon MG, Steinberg SV (2002). GU receptors of double helices mediate tRNA movement in the ribosome. RNA 8: 873–877