Killam Seminar Series: Chasing Shape-Shifting Condensates Linked to ALS with Proteomics
Gr芒ce 脿 la g茅n茅rosit茅 des fiducies Killam, Le Neuro convoque lors d鈥檜ne s茅rie de s茅minaires des conf茅renciers d鈥檈xception dont les travaux passionnent ses chercheurs et ceux de l鈥橴niversit茅 平特五不中.听
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Ji-Young Youn, PhD
Chercheuse, Institut de recherche SickKids, Professeure adjointe, Universit茅 de Toronto, Canada
贬么迟别:听gary.armstrong [at] mcgill.ca (Gary Armstrong)
Abstract:听Amyotrophic 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.
