Characterising the interactome of sequestosome-1 (p62) – the peacemaker between protein homeostasis and dysfunction

Protein clearance pathways and aggregate formation have recently been associated with dysfunctional biomolecular condensates. One protein commonly identified in aggregates in ALS is Sequestosome-1/p62. This study will combine proteomic, optogenetic and bioinformatic approaches to investigate how p62 biomolecular condensates are involved in ALS states. We aim to identify how p62 domains and ALS-linked proteins alter the interactome of p62 to disrupt its biomolecular properties, leading to protein aggregation. These studies will provide valuable insight into a newly described process in ALS and potentially identify a therapeutic target to be leveraged for ALS treatment.