
Study of the kinetics of amyloid fiber formation by thioflavin-T and transmission electron microscopy
Project description
Amyloidoses are a set of diseases associated to depositions of insoluble protein aggregates, named amyloid fibrils. The majority of these diseases remain orphans due to challenges in their rarity or challenges in their diagnostic and treatment. The common trait of these diseases is the peptide/protein misfolding that aggregate in insoluble amyloid deposits. These deposites can be localized or systemic, at the level of several tissues or organs. Considering that prefibrillar species are highly toxic for cells and that they seem to lie at the origin of the tissue degeneration, a better understanding of molecular events preceding amyloid fibrils formation will allow the development of pre-emptive diagnostic assays and/or new therapeutic approaches to inhibit the formation of transitionary cytotoxic species. Our hypothesis is that conformational transitions of oligomeric aggregates to a stable nucleus play a key role in the mechanistic basis of amyloid fibrils formation and in the existence of toxic species that form a large conformational ensemble. For this reason we propose to study the effect of perturbations of non-structured oligomer formation by favoring a secondary structure at the monomer level to control the kinetics of amyloid auto-assembly and the presence of cytotoxic species.
Research team
Name: Margaryta Babych, M.Sc
Supervisor: Steve Bourgault (UQAM)
Laureate: Doctoral fellowship 2019
