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.

DARA FOOTPRINT

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