Département de biochimie
Cellular dynamics of protein complexesThe sequencing of genomes and following proteomics analyses have revolutionized our understanding of fundamental processes in living organisms. The next challenge of research will be to understand the dynamic interactions between cell components, for example between proteins and their complexes that determine cell structure and most cellular processes. Our laboratory conducts research on two different projects:1. Type IV secretion systems – a group of 12 proteins in the bacterial cell envelope. They assemble into a complex that transfers macromolecules (DNA or proteins) into other bacteria or into eukaryotic cells. The translocation of proteins into eukaryotic cells facilitates bacterial survival and is important for many pathogens. In addition, type IV secretion systems transfer DNA molecules between bacteria and this contributes to the spread of antibiotic resistance genes. The goal of our research is to understand the assembly process and the mechanism of type IV secretion systems. Based on the results of our work, we will develop small molecule inhibitors for basic research on protein complexes as well as anti-virulence drugs that disarm bacterial pathogens and improve the treatment of infectious diseases.2. Biosynthesis and incorporation of selenocysteine into proteins – The 21st amino acid selenocysteine is present at the active site of many enzymes and it is essential for human life. Selenocysteine biosynthesis proceeds attached to a specific tRNA and necessitates several proteins as well as specialized translation factors that guide the incorporation at UGA codons of certain mRNAs. Goal of our research is to understand the molecular basis and the dynamics of protein and RNA interactions involved in selenocysteine metabolism. This work will contribute to the understanding of human diseases that are linked to the functioning of selenoproteins.In our laboratory we apply methods of molecular biology, protein biochemistry, structural and chemical biology and of high-thoughput screening, which provides the members of our group with broad experience. We are members of a trans-Canadian training program with shared research interests in the cellular dynamics of macromolecular complexes (CDMC) and we also pursue collaborations with members of the membrane protein research group (GÉPROM) and of the medicament research group (GRUM).
- Baron, C. (2013) A novel strategy to target bacterial virulence. Future Microbiol. 8:1-3
- Smith, M.A., Coinçon, M., Paschos, A., Jolicoeur, B., Lavallée, P., Sygusch, J. and Baron, C. (2012) Identification of the binding site of Brucella VirB8 interaction inhibitors. Chemistry and Biology 19:1041-8
- Villamil-Giraldo, A.-M., Sivanesan, D., Carle, A., Paschos, A., Smith, M. A., Plesa, M., Coulton, J. and Baron, C. (2012) The type IV secretion system core component VirB8 from Brucella binds to the globular domain of VirB5 and to a periplasmic domain of VirB6. Biochemistry 51: 3391-3390
- Sivanesan, D. and Baron, C. (2011) The dimer interface of Agrobacterium tumefaciens VirB8 is important for type IV secretion system function, stability, and association of VirB2 with the core complex. J. Bacteriol. 193:2097-106
- Paschos, A., den Hartigh, A., Smith, M.A., Atluri, V.L., Sivanesan, D., Tsolis, R.M. and Baron, C. (2011) An in vivo high-throughput screening approach targeting the type IV secretion system component VirB8 identified inhibitors of Brucella abortus 2308 proliferation. Infect .Immun. 79:1033-43
- Sivanesan, D., Hancock, M.A., Villamil Giraldo, A.M., Baron, C. (2010) Quantitative analysis of VirB8-VirB9-VirB10 interactions provides a dynamic model of type IV secretion system core complex assembly. Biochemistry 49:4483–4493
- Baron, C. (2010) Antivirulence drugs to target bacterial secretion systems. Curr. Opin. Microbiol. 13:100-1055.