Jefferson Matthew Taliaferro
University of Colorado Denver/Anschutz Medical Campus, CO·Biochemistry
Cells are not uniform bags of molecules. Different regions of a cell carry out different jobs, and one way cells put the right proteins in the right place is by shipping RNA molecules, the working copies of genes, to specific locations and making proteins there.
- Fields
Biochemistry
Genetics
Neuroscience
- Topics
RNA localization
subcellular transcriptomics
amyotrophic lateral sclerosis
- Grants
- 2 known grants, through Jul 2029
What they work on
- 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.
- Define the RNA sequence features that make transcripts depend on TDP-43 for transport, and test whether these features are necessary and sufficient using reporter transcripts.
- Visualize TDP-43-mediated transport of single RNA and protein molecules in live Drosophila brains to learn how this transport is regulated and how fast it moves.
- Test whether removing TDP-43 recognition sequences from specific fly RNAs, so those RNAs are misplaced, causes the movement and physiological defects seen in TDP-43 mutant flies and ALS patients.
- Discover RNA 'zip code' sequences and the RNA-binding proteins that read them by isolating subcellular transcriptomes and finding features shared by RNAs at the same destination.
- Characterize in depth how known RNA localization elements work, and develop new technologies to study RNA localization in organisms and cell types that have been hard to study.
More about the research
Neurons face this problem in its most extreme form, because their long axons and dendrites stretch far from the cell body. When RNA delivery goes wrong, the result can be developmental defects or neurological disease. Yet much less is known about the rules of RNA localization than about other kinds of RNA control, such as splicing. Two projects tackle this gap. One is a broad effort to decode the general 'language' of RNA localization. The other applies that thinking to ALS, amyotrophic lateral sclerosis, a fatal disease that destroys motor neurons.
Why it matters
Many neurological diseases, including ALS, involve mutations in proteins that keep RNAs in their proper place inside neurons. Identifying which RNAs are misplaced in ALS motor neurons, and linking those errors to symptoms, could reveal an overlooked disease mechanism and new targets for treatment. More broadly, rules for predicting where RNAs travel could help researchers understand disorders that arise from faulty RNA transport across many cell types.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
John Buchan
University of Arizona, AZ·Biochemistry
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.
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.
Lin Guo
Thomas Jefferson University, PA·Biochemistry
Determine how the nuclear import receptor Kapβ2 engages and chaperones newly found partner proteins that lack a nuclear localization signal, using cryo-electron microscopy to solve their structures.
The school
University of Colorado Denver/Anschutz Medical Campus: 41 labs on PI Pages, $766M a year on research, 205 research doctorates a year.
More about University of Colorado Denver/Anschutz Medical Campus
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