"Establishing Sacsin’s Interacome and Completing the First High-Throughput Drug Screen Using an ARSACS Fibroblast Essay"– Dr. Bernard Brais and Dr. Eric Shoubridge

In Current Research by ARSACS

Aim 1: Moving from HEK293 sacsin’s interactome to neuronal sacsin partners. Aim 1.2. Study the impact of lack of sacsin or mutated sacsin on identified partners.

Aim 2: Perform high-throughput drug screening using our ARSACS fibroblast assay to identify molecules that rescue the cytoskeletal phenotype.  further validation (2.2). Aim 2.2 Validations of candidate drugs. 2.2.1 Drugs that successfully restore the vimentin network in ARSACS 366 cell lines will undertake a second screen. In this second assay we will include other ARSACS cell lines as well as our CRISPR/Cas9 Sacs-/- fibroblasts. We will also assay different drug concentrations to establish dose response curves. 2.2.2 Drugs that successfully pass this second screen will be used to evaluate their effect on mitochondrial network, which was shown to be disrupted in ARSACS cells (Girard et al., (2012) by standard immunofluorescence and mitochondrial respiratory function by oxygraphy.

Duration: one year
Grant: $100,000
Contacts:

Dr. Bernard Brais

Dr. Bernard Brais

Dr. Bernard Brais, co-director of the neuromuscular group of the Montreal Neurological Institute and Hospital
3801 University Street Montreal, Quebec, Canada H3A 2B4
Tel:(514)-398-3334; Email: bernard.brais@mcgill.ca

Dr Eric Shoubridge

Dr Eric Shoubridge

Dr. Eric Shoubridge, Montreal Neurological Institute and Hospital
3801 University Street Montreal, Quebec, Canada H3A 2B4
Tel: (514)-398-1997; Email: eric.shoubridge@mcgill.ca