How C9orf72 RNA repeats make toxic proteins in ALS and FTD
Deciphering the structural basis of repeat-associated non-AUG (RAN) translation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
This research looks for how a repeated RNA sequence in the C9orf72 gene creates toxic proteins that can harm people with ALS or FTD.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Michigan at Ann Arbor NIH-funded |
| Lab location | 1 site (Ann Arbor, United States) |
| Project ID | NIH-11194424 on NIH RePORTER |
What this research studies
Researchers will use high-resolution cryo-electron microscopy along with lab-based biochemical and genetic tests to see how the repeated GGGGCC RNA sequence interacts with the cell’s protein-making machinery (the ribosome). They will map how translation starts without a normal start signal to produce dipeptide repeat (DPR) proteins that build up in affected brains. The team will also search for neuronal proteins that transiently bind the ribosome and promote this abnormal translation. Combining structural images with experiments should reveal the precise molecular steps that lead to toxic protein production.
Who could benefit from this research
Good fit: The most relevant people would be individuals with ALS or FTD who carry the C9orf72 hexanucleotide repeat expansion, or family members interested in research participation.
Not a fit: People with ALS or FTD caused by other genes or without the C9orf72 repeat expansion are unlikely to see direct benefits from this project in the short term.
Why it matters
Potential benefit: If successful, this work could reveal targets to block toxic protein production and guide new treatments for people with C9orf72-linked ALS or FTD.
How similar studies have performed: Prior studies have shown that C9orf72 repeats produce toxic DPR proteins and harm neurons, but the detailed structural mechanism of how RAN translation starts is largely untested and this cryo-EM approach is novel.
Where this research is happening
Ann Arbor, United States
- University of Michigan at Ann Arbor — Ann Arbor, United States (Active)
Researchers
- Principal investigator: Brito Querido, Jailson — University of Michigan at Ann Arbor
- Study coordinator: Brito Querido, Jailson
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.