John Buchan
University of Arizona, AZ·Biochemistry
Cells must constantly clean up clumps of RNA and protein, because leftover clumps can become toxic. Failures in this cleanup are linked to amyotrophic lateral sclerosis (ALS), a fatal disease that destroys the nerve cells controlling movement, and to some cancers and viral infections.
- Fields
Biochemistry
Biology
Neuroscience
- Topics
stress granules
P-bodies
mRNP granules
- Grants
- 1 known grant, through May 2027
What they work on
- Define how much each reported clearance route contributes to removing stress granules and P-bodies under disease-relevant stress, and how the routes cooperate. Use genetic, biochemical and cell biology assays in yeast and human cells.
- Identify the mechanism of granulophagy, the selective recycling of RNA-protein granules. Test a model from an unbiased yeast screen, and use a new stress granule purification method to find granule-localized effectors.
- Measure which RNAs are destroyed in vacuoles and lysosomes, the cell's digestive compartments. Combine vacuole isolation with RNA sequencing, then use genetics and single-molecule imaging to find how these RNAs are delivered.
- Test whether the ALS-linked protein TDP-43 is degraded when endosome membranes fold inward to capture it. Build on a yeast screen for regulators of TDP-43 levels, and assess effects on neurons and TDP-43-related RNA defects.
More about the research
This project asks how cells break down or take apart these clumps, and what happens to cells when the cleanup goes wrong.
Why it matters
Faulty clearance of RNA-protein clumps may contribute to the onset and progression of ALS and of some cancers. By showing how cells clear stress granules and the toxic, mislocalized TDP-43 protein, this work may point to therapeutic targets. It could also suggest ways to boost the body's own clearance processes in these diseases. Mapping an overlooked RNA decay pathway in vacuoles and lysosomes could also show how such breakdown shapes which genes cells use.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xin Jie Chen
Upstate Medical University, NY·Biology
Test in yeast whether specific mitochondrial stresses cause severe protein-handling damage to the vacuole, the yeast lysosome. Use genetic screens to find genes that suppress this signaling and may extend lifespan.
Jefferson Matthew Taliaferro
University of Colorado Denver/Anschutz Medical Campus, CO·Biochemistry
Identify RNAs that are mislocalized in human stem-cell-derived motor neurons that lack TDP-43, carry ALS-linked TDP-43 mutations, or come from ALS patients, using a transcriptome-wide RNA mislocalization assay.
Jingjing Liang
University of Arizona, AZ·Neuroscience
Test how Aggregatin, a protein encoded by the Alzheimer's-linked gene FAM222A, controls TDP-43 clumping and toxicity in neurons, using Aggregatin knockout models.
The school
University of Arizona: 36 labs on PI Pages, $1.0B a year on research, 487 research doctorates a year.
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