Killam Seminar Series: Chasing Shape-Shifting Condensates Linked to ALS with Proteomics
Supported by the generosity of the Killam Trusts, The Neuro's Killam Seminar Series invites outstanding guest speakers whose research is of interest to the scientific community at the MNI and Â鶹AV.
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Ji-Young Youn, PhD
Scientist, SickKids Research Institute, Assistant Professor, University of Toronto, Canada
Host:Ìýgary.armstrong [at] mcgill.ca (Gary Armstrong)
Abstract:ÌýAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no known cure. A hallmark of ALS is the cytoplasmic aggregation of TAR DNA-binding protein 43 (TARDBP, called TDP-43 here). TDP-43 is an essential DNA/RNA-binding protein with multiple roles in post-transcriptional regulation. Harboring prion-like domain, TDP-43 readily phase separates in vitro and localizes to biomolecular condensates formed by cellular phase separation. Aberrant phase transition of TDP-43, accelerated by ALS-associated mutations or stress, are thought to underly ALS pathogenesis. However, the functional consequences of altering TDP-43 phase separation properties remain poorly understood. In this talk, I will share our efforts to characterize ALS-associated TDP-43 variants with altered phase separation dynamics. Exploiting proximity-dependent biotinylation techniques, we examine quantitative changes in proximal interaction networks of TDP-43 variants or TDP-43 wildtype during stress. Our preliminary data reveal unanticipated functions of TDP-43 controlled by phase separation.
