The Buchan lab studies diverse topics related to RNA biology and proteostasis, spanning both basic and translational topics of research. We utilize yeast (S.cerevisiae) and various human cell line models, and apply a variety of genetic, cell biology and biochemical approaches in our work.
Historically, we have focused on characterizing the dynamics, composition and function of stress granules and P-bodies, which are membraneless biomolecular condensates enriched in non-translating mRNA-protein complexes (mRNPs), as well as a range of other non-coding RNAs and proteins of diverse function. An ongoing project is in studying the clearance mechanisms of these granules, dysregulation of which has been suggested to play an important role in the pathological mechanisms in Amyotrophic Lateral Sclerosis (ALS), other related neurodegenerative diseases and various cancers. Other related projects include compositionally assessing stress granules and P-bodies under conditions of interest, and determining the consequences of various biomolecules being sequestered in these condensates.
More recently, we have characterized a novel endolysosomal degradation mechanism by which TDP-43, an RNA-binding aggregation prone protein implicated in ALS pathology, is cleared in eukaryotic cells. Ongoing work here focuses on the precise molecular mechanisms of such clearance. We are also interested in how various TDP-43 proteostatic mechanisms interface under distinct conditions to limit the cytoplasmic mislocalization, accumulation and aggregation that is typically seen in ALS patients, and patients of other TDP-43 proteinopathies.
Finally, we have an interest in novel functions of mRNA 3’UTR sequences, in particular a means by which 3’UTRs may help scaffold nascently translated protein interactions by recruiting binding partner proteins.