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Roles of glycosaminoglycans in membrane perturbation and cytotoxicity induced by amyloidogenic proteins

Image by transmission electron microscopy of amyloid fibers of the amyloid polypeptide islet, the scale is 100 nm.

Project description

Amyloidosis includes numerous orphan diseases characterized by the tissue accumulation of insoluble proteins in the form of amyloid fibrils. For instance, in patients afflicted by AL amyloidosis, the protein immunoglobulin light chain accumulates in numerous tissues. Recently, it has been shown that cell and tissue degeneration is mainly mediated by intermediates of the amyloidogenic cascade and not by the deposition of amyloid fibrils. Besides, many biological macromolecules, such as glycosaminoglycans, can modulate the self-assembly and toxicity of amyloidogenic polypeptides. Thus, a better understanding of the mechanisms of toxicity as well as the involvement of biological macromolecules in the pathological process is critical to treat amyloidosis. In this study, two amyloidogenic polypeptides will be used, an isoform of the immunoglobulin light chain and the peptide islet amyloid polypeptide, which is associated with type II diabetes. The self-assembly of these amyloidogenic polypeptides in a complex biological environment will be studied using state-of-the-art biophysical approaches. In parallel, membrane disruption induced by the self-assembly process will be assessed by confocal microscopy and cell-based assays. Overall, this project will provide a better understanding of the molecular mechanisms of amyloidosis and could lead to the identification of novel therapeutic targets.

Research team

Name: Noé Quittot, M.Sc.
Supervisor: Steve Bourgault (UQAM)
Laureate: Doctoral fellowship 2018

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