Summary
Investigating the RNA-Regulatory Activities of the RNA Exosome during Human Motor Neuron Differentiation to understand post-transcriptional control in neurodevelopmental disorders.
Investigating the RNA-Regulatory Activities of the RNA Exosome during Human Motor Neuron Differentiation
US · IL
NIH
grant
awarded
#nih-1F31NS143348-01
What they want
The project aims to investigate the function of the RNA exosome during neuronal differentiation, specifically in human spinal motor neurons. It will utilize human induced pluripotent stem cells (hiPSCs), engineered via CRISPR technology, to model RNA exosome-linked motor neuron diseases such as severe PCH1b (EXOSC3-G31A), mild PCH1b (EXOSC3-G191C), and a novel NDD linked to a mutation in EXOSC4 (EXOSC4-L187P). The research will study the impact of pathogenic EXOSC3/4 mutations on human spinal motor neuron differentiation using a 2D cell culture method. The hypothesis is that disease-linked mutations in EXOSC3/4 alter RNA exosome function, leading to an accumulation of pathogenic RNA species that cause spinal motor neuropathy.
Deliverables
- A comprehensive analysis of how pathogenic mutations in RNA exosome subunit genes impact post-transcriptional regulation during human neuronal differentiation
- Insight into pathological mechanisms underlying RNA-mediated motor neuropathy
Technical requirements
- Human induced pluripotent stem cells (hiPSCs) engineered via CRISPR technology
- 2D cell culture method
