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Bourgault, Steve

Steve Bourgault

University of Quebec in Montreal

Date: Wednesday, June 15, 2022
Talk Time: 02:20 pm - 02:40 pm
Talk Title: Manipulating Peptide Self-Assembly into cross-β-sheet Supramolecular Structures to Design Synthetic Nanovaccines

Professor Steve Bourgault received his BSc in Biochemistry from Université du Québec à Montréal in 2002 before completing a MSc in experimental health sciences, specialization in molecular pharmacology, at INRS-Institut Armand-Frappier. He received his Ph.D., joint doctoral thesis, in 2009 from both INRS-Institut Armand-Frappier in biology and the Université de Rouen, France, in biology – option in medicinal chemistry – under the co-supervision of Professors Alain Fournier and David Vaudry.

His graduate research work focuses on the molecular pharmacology and medicinal chemistry of peptide hormones, on the development of synthetic methods for solid phase peptide synthesis and on the structural study of polypeptides.

After receiving his Ph.D., Steve Bourgault started his postdoctoral training at the Department of Chemistry of The Scripps Research Institute in La Jolla, CA, USA, under the supervision of Professor Jeffery W. Kelly, a world-leader in the field of protein misfolding diseases. His research work focused on the biochemical mechanism of transthyretin amyloidoses, which are an important class of senile and/or familial protein misfolding disorders. In 2012, Dr Bourgault moved back to Montreal where he started his independent scientific career as an Assistant Professor at the Department of Chemistry of UQAM.

Amyloid fibrils, historically associated with diseases, have been recognized as a biological structure that performs essential functions in many host organisms, highlighting their potential as life-inspired nanoparticles, soft biomaterials, and matrices. These cross-β-sheet organized proteinaceous assemblies combine key characteristics, including high mechanical resistance, biocompatibility, biodegradability, and chemical and enzymatic stability.

We are currently developing nanoassemblies based on the cross-β quaternary motif as adjuvanted antigen delivery system. Our strategy relies on the covalent attachment of an immunological epitope to a self-assembling peptide unit. Upon self-recognition of the chimeric peptide, tailored nanostructures displaying multiple copies of the antigen are obtained.

These fibrils are efficiently uptaken by antigen-presenting cells, and the cross-β-sheet architecture readily activates the Toll-like receptor 2 and stimulates dendritic cells, leading to a robust antigen-specific immune response in mice. To address the inherent polymorphism and polydispersity associated with the process of amyloid formation, we conceived a strategy to finely control the architecture from the peptide sequence.

Addition of electrostatic capping motifs on the β-peptide leads to short, rigid, and uniform nanorods. Mice intranasal immunization with these nanorods, decorated with a highly conserved epitope from the influenza A virus, confers complete protection with absence of clinical signs against a lethal infection with the H1N1 strain. We also harnessed this approach to prepare synthetic carbohydrate vaccines to fight bacterial infections.

Overall, these studies reveal that by acting as an immunomodulator and an antigen delivery system, peptide cross-β-sheet assemblies constitute robust and versatile nanoplatforms for subunit and glycoconjugate vaccines.

Steve Bourgault, talk image 2

Steve Bourgault
Steve Bourgault, talk image 1
Steve Bourgault, talk image 3
Steve Bourgault, talk image 4