Jayson Smith
Syracuse University, NY·Genetics·Early-career
Every neuron in the body ends up with a specific job, and it has to keep doing that job for decades. The instructions come from "terminal selectors" — master switch proteins that turn on the genes giving a neuron its final working identity.
- Fields
Genetics
Neuroscience
Biology
- Topics
motor neurons
terminal selector
transcription factor
- Grants
- 1 known grant, through Jul 2029
What they work on
- 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.
- Determine how UNC-3 affects GABA motor neurons that never express unc-3 themselves, confirming these non-cell-autonomous gene-expression changes in living worms and running a suppressor genetic screen to identify the intervening mechanism.
- Ask whether the human UNC-3 counterparts EBF1 and EBF3 control terminal identity genes in human motor neurons, using small hairpin RNA knockdown in motor neurons derived from human embryonic stem cells paired with single-cell RNA sequencing.
- Build a validated map of direct UNC-3 target genes by combining existing ChIP-Seq binding data, which predicted more than 3,500 candidate targets, with in vivo expression testing of individual terminal identity genes.
More about the research
For motor neurons, the cells that tell muscles to contract, failures in this program are linked to devastating conditions such as amyotrophic lateral sclerosis (ALS), a disease with no effective treatment. Part of why treatments are missing is that we still do not know the full set of genes a terminal selector controls, or whether it also influences neighboring neurons that never switch it on.
Why it matters
Motor neuron diseases such as ALS remain untreatable in part because the gene programs that build and maintain motor neurons are poorly mapped. Clarifying how UNC-3 and its human relative EBF3 control these programs could improve laboratory recipes for making motor neurons from stem cells for disease modeling, and could explain the symptoms of EBF3 Syndrome, a neurodevelopmental disorder caused by mutations in this gene.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
John Rubenstein
University of California-San Francisco, CA·Neuroscience
Identify genes that differ across time and region in the medial ganglionic eminence (MGE) using enhancer-CreER mouse labeling and single-cell RNA-seq, and study Nfia/b/x and Tcf7l2 mutant mice.
Eran Andrechek
Michigan State University, MI·Genetics
Characterize mammary gland defects in mice lacking E2F5 only in mammary epithelial cells, including duct extension during puberty, alveolar development and involution.
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
Syracuse University: 13 labs on PI Pages, $199M a year on research, 168 research doctorates a year.
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