Jacob Niklassen



Cohort 2026
Mechanisms of Pathogenic RNA-Protein Condensates in Amyotrophic Lateral Sclerosis
This project investigates how Amyotrophic lateral sclerosis (ALS)-causing mutations alter RNA-protein condensates (RPCs). RPCs are dynamic cellular compartments that organize RNAs and proteins. By mapping the RNA and protein composition of RPCs in motor neurons, the project aims to understand how these condensates transition from healthy to disease-associated states.
ALS is a devastating neurodegenerative disease with limited treatment options. Many ALS mutations affect RNA-binding proteins, but it remains unclear why motor neurons are especially
vulnerable. Understanding how RNA-protein condensates become dysfunctional may reveal new disease markers and therapeutic targets.
Using engineered cell models and human stem-cell-derived motor neurons, I will identify the proteins and RNAs found in ALS-associated condensates. I will combine proximity labeling, condensate purification, mass spectrometry, RNA sequencing, imaging, and advanced bioinformatics to investigate how key candidates affect neuronal health.
