Jacob Niklassen



Mechanisms of Pathogenic RNA-Protein Condensates in Amyotrophic Lateral Sclerosis
What? 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.
Why? 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.
How? 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.
