Gary Bassell
Emory University, GA·Neuroscience
Neurons are long, highly branched cells, and many of the proteins they need are built far from the cell body, close to synapses. To manage this, neurons ship messenger RNAs (mRNAs) — the instructions for making proteins — out to distant sites and translate them locally, and they continually move proteins on and off their surface.
- Fields
Neuroscience
Genetics
Biology
- Topics
mRNA transport
local translation
RNA binding proteins
- Grants
- 2 known grants, through Jun 2027
What they work on
- Identify the RNA binding proteins and mRNA cargoes carried by the kinesin motor KIF1C, and test whether SPG58 pathogenic variants alter that binding, using mass spectrometry in CRISPR-generated KIF1C knockout human iPSC-derived motor neurons.
- Track how KIF1C and its pathogenic variants move, using live imaging of the motor and its RBP and mRNA cargoes in human motor neurons, and test whether expressing selected variants rescues mislocalized cargo.
- Test whether FMRP normally represses synthesis of AP2 subunits, the endocytic adaptor complex, and whether elevated AP2 at synapses causes the reduced surface AMPA receptor levels seen in Fragile X mouse neurons, using viral shRNA knockdown and drug inhibition.
- Determine whether elevated AP2 also lowers surface levels of the other membrane proteins found in the lab's biotinylation screen, following receptors through CRISPR-Cas9 knock-in of fluorescent SEP tags on endogenous GluA1 and GluA2.
More about the research
Both processes falter in neurological and neurodevelopmental disease, and this lab and others have found defects in mRNA transport and local translation in spinal muscular atrophy, Fragile X syndrome, amyotrophic lateral sclerosis and myotonic dystrophy. Two current projects pursue this theme: one in a hereditary movement disorder caused by a broken molecular motor, the other in the most common inherited intellectual disability.
Why it matters
Hereditary spastic paraplegia type 58 and Fragile X syndrome lack treatments that address their root causes. Identifying which RNA cargoes depend on KIF1C in human motor neurons could reveal disease-specific targets in SPG58 and other disorders of neuronal transport. Showing that excess AP2 drives loss of surface receptors in Fragile X syndrome could make AP2 a candidate target for correcting impaired synapse development in affected children.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
Jayson Smith
Syracuse University, NY·Genetics·Early-career
Test whether UNC-3 acts as both an activator and a repressor of neuronal identity genes, by validating the thousands of up- and downregulated genes found in single-cell RNA sequencing of adult wild-type and unc-3 mutant C. elegans cholinergic motor neurons.
Peter Baas
Drexel University, PA·Neuroscience
Test whether lysosome-targeting intrabodies, antibody fragments made inside cells, effectively and sustainably deplete toxic mutant M1 spastin in hiPSC-derived motor cortical organoids without off-target toxicity.
The school
Emory University: 70 labs on PI Pages, $1.2B a year on research, 286 research doctorates a year.
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