Mechanisms of amyloid formation: a focus on the islet amyloid polypeptide and immunoglobulin light chain
Protein aggregation and amyloid deposition are associated with diseases as diverse as Alzheimer’s disease, diabetes mellitus type 2 (DM-2), Creutzfel-Jakob disease and numerous amyloidoses. Owing to the increase of human lifespan, prevalence of protein misfolding/aggregation diseases increased considerably over the last decades. The laboratory of Pr Bourgault is studying the mechanisms by which the peptidic hormone islet amyloid polypeptide (IAPP) and the immunoglobulin light chain (LC) protein self-associate to form these well-defined amyloid fibrils. By combining chemical biology, biophysics and biochemistry, we aim at elucidating the roles of the microenvironment and the (transient) interactome on the kinetics and pathway of amyloidogenesis and at developing (bio)chemical approaches to control the assembly of IAPP and LC.
Physiological roles of peptide-glycosaminoglycan interactions: a biophysical and biochemical characterization
Peptides are important biomolecules that play key biological roles by acting as hormones, neurotransmitters, antibiotics and/or growth factors. To perform its biological(s) function(s), a polypeptide chain needs to adopt a specific tri-dimensional structure, allowing the precise positioning of its pharmacophoric elements. Interestingly, several long and linear biologically active peptides exhibit mainly a random coil structure; i.e. they lack a specific conformation when they are not associated with their binding partner(s). Pr Bourgault’s team is studying how the interactions of natively disordered peptidic hormones with glycosaminoglycans (GAGs) modulate their conformation ensemble and biological function.
The amyloid structure: a novel strategy for the formulation of peptide therapeutics
The amyloid fibrils are well-organized nanostructures that results from the self-assembly of a given polypeptide chain. These molecular structures have been historically associated with pathological conditions, although several recent studies have reported that they also play important and vital biological functions. Interestingly, these protein nanostructures are dynamic and they could be generated by the vast majority of natural polypeptides. Accordingly, the group of Pr Bourgault, in collaboration with Pr Marcotte and Pr Rouiller, is evaluating the usage of amyloid fibrils as a novel formulation/delivery approach for peptide therapeutics. We are probing the relation between the supramolecular organization, the molecular architecture and the stability to develop amyloids with precise dynamic properties.
Novel protein adjuvants for vaccines:
chemical synthesis of small proteins by chemical ligation
Adjuvants constitute a unique class of pharmacological compounds that modulate the effects of other immunological agents. These molecular identities are usually employed in combination with vaccine to boost the immunological response. In collaboration with Pr Archambault, we are developing novel protein-based adjuvants by chemical