Sim Lab: Projects
We have several active projects in the lab right now.
1. Organotypic cultures
We use a prion organotypic slice culture assay in which mouse cerebellar slices are cultured long-term and infected with different strains of prions. These cultures undergo pathology as seen in vivo. We are adapting these cultures to different brain regions, different prion strains, and different host species. We are investigating why different prion strains preferentially target particular brain regions. We are also investigating which death pathways are activated early in prion infection, with the goal of discovering treatment targets.
2. Prion protein alleles
We have found that small allele polymorphisms can translate into different aggregation behaviours of the prion protein in vitro. We are now investigating these allelic properties in cell model systems infected with bona fide infectious prions. This will help shed light on how prion strains may adapt in new hosts, and help predict the risk of transmission within and across species barriers, in particular, for chronic wasting disease.
We are exploring different compounds that can prevent prion conversion, improve prion clearance, and / or prevent cell death. In particular, we are looking at how combination therapy with treatments that target different parts of the pathogenic pathway may lead to better outcomes than any single agent.
4. Alzheimer's disease
We are applying prion science techniques to the world of amyloid beta (Abeta) and tau, which are proteins that accumulate in Alzheimer's disease. This includes development of interfering peptides to be used as therapeutics or amyloid tracers, adaptation of organotypic cultures for the propagation of Abeta and tau, and characterization of Abeta and tau strains in different phenotypes of Alzheimer's disease.
Last updated: 2019-05-31