Human-specific splicing regulation in neurogenesis and disease
Ended Project Grant Awarded Last action
- Award ID
- F32NS138224
- Recipient
-
Duke University UEI TP7EK8DZV6N5
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $195,889
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date
- Place of performance
- Durham, NC 27705, USA
Award details come from USAspending.gov.
Description
- Abstract
- The cortex is responsible for many of our uniquely human cognitive abilities and distinguishes our closest evolutionary relatives. Humans diverged from chimpanzees ~7MYA and have accumulated several genomic differences that could help explain human-specific aspects of cortical development. Many of the genomic differences between humans and chimpanzees are in non-coding elements where they have been traditionally studied as regulators of gene expression. In this proposal, i provide preliminary evidence that indicates additional roles for these human-specific sequences in post-transcriptional gene expression. Over 40% of these human- specific sequences are found within introns where i hypothesize, they contribute to the regulation of splicing during human-specific neurodevelopment. In aim 1, i will test the function of intronic human-specific sequences to enhance and repress splice sites and ultimately alter species-specific isoform expression. Next as a proof of concept, in aim 2 i will investigate the consequences of changes in splicing and isoform production in neurodevelopment. Specifically, i will be testing changes in splicing associated with an autism-associated SNP in the intron of tenascin c (TNC). The SNP is located in a human-specific sequence and reverts the intronic sequence back towards the chimpanzee sequence. The proposed research will define a novel mechanism of action for human-specific non-coding regions of the genome in the regulation of post-transcriptional RNA processing during cortical development and disease.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | -$25,595 | |
| Amendment | $73,828 | |
| Amendment | $0 | |
| Amendment | $73,828 | |
| Amendment | $0 | |
| Original award | $73,828 |
Quick answers
Who received award F32NS138224?
F32NS138224 was awarded to Duke University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on June 16, 2025.
How much is award F32NS138224 worth?
$195,889 has been obligated on F32NS138224.
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