Jailson Brito Querido
University of Michigan, MI·Biochemistry
Cells normally begin building a protein at a specific start signal in its messenger RNA (mRNA), the AUG codon. In the most common inherited form of ALS (amyotrophic lateral sclerosis) and frontotemporal dementia (FTD), this rule breaks down.
- Fields
Biochemistry
Biophysics
Neuroscience
- Topics
RAN translation
repeat-associated non-AUG translation
C9orf72
- Grants
- 1 known grant, through Aug 2029
What they work on
- Determine how expanded GGGGCC repeats in C9orf72 mRNA physically engage the ribosome to trigger non-AUG start site selection, using cryo-electron microscopy with biochemical and genetic approaches.
- Identify proteins in neurons that bind the translation initiation complex briefly and with low affinity, and test whether they promote RAN translation of C9orf72 mRNA.
- Develop an approach for studying mRNA translation initiation in its native neuronal environment, applicable to other neurodegenerative diseases involving aberrant translation.
More about the research
A six-letter GGGGCC repeat in the C9orf72 gene is greatly expanded. Although the repeat sits in an intron, a region usually removed from the mRNA, it stays in the mature mRNA. Ribosomes then translate it without an AUG start, a process called repeat-associated non-AUG (RAN) translation. This produces toxic dipeptide repeat (DPR) proteins that clump in patients' brains and cause neurodegeneration in model systems. How RAN translation starts remains unknown.
Why it matters
Toxic dipeptide repeat proteins from C9orf72 RAN translation contribute to ALS and frontotemporal dementia. A structural picture of how this faulty translation starts, and which neuronal proteins promote it, could reveal points where it might be blocked. It could also guide studies of other diseases driven by aberrant mRNA translation.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Hannah Shorrock
University at Albany, NY·Genetics·Early-career
Measure how much of the human genome can undergo multi-frame translation (MFT), using a new reporter system that detects protein made in several reading frames, in a genome-wide screen.
Bruce Armitage
Carnegie Mellon University, PA·Chemistry
Design fluorescent peptide nucleic acid (PNA) probes that bind unmodified C9orf72 repeat RNAs, so these RNAs can be seen in biomolecular condensates by microscopy.
X. Shawn Liu
Columbia University, NY·Neuroscience
Test whether reactivating the healthy MECP2 copy on the silenced X chromosome, by removing promoter methyl tags with dCas9-Tet1, rescues Rett syndrome symptoms in female mouse models.
The school
University of Michigan: 124 labs on PI Pages, $2.1B a year on research, 963 research doctorates a year.
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