The role of retrotransposonable elements in neurodevelopment and disease
Ended Project Grant Awarded Last action
- Award ID
- F32HD114499
- Recipient
-
Cleveland Clinic Lerner College Of Medicine Of Case Western Reserve University UEI M5QFLTCTSQN6
- Awarding agency
-
National Institute of Child Health and Human Development
National Institutes of Health, Department of Health and Human Services
- Obligated
- $364,324
Award facts
- Assistance listing
- 93.865 Child Health and Human Development Extramural Research
- Completion date
- Place of performance
- Cleveland, OH 44195, USA
Award details come from USAspending.gov.
Description
- Abstract
- Retrotransposable elements (rtes) are genomic elements that have the ability to "copy-and-paste" themselves into new locations within the genome. RTE mobilization can cause mutations and genomic instability. Many cellular mechanisms exist to repress RTE activity. Interestingly, IT has been observed that neural stem and progenitor cells (nspcs) show high levels of RTE activity. However, IT is currently unknown whether this RTE activity is essential for normal development of the brain. Further, abnormally high RTE activity has been associated with a number of neurodevelopmental disorders. Causative roles for RTE expression and mobilization in neurodevelopmental disorders have not been identified. The long term objectives of this proposal are to understand whether RTE activation is necessary for normal development and whether RTE inhibition is a viable treatment for neurodevelopmental disorders. In my first specific aim, i will test the impact RTE expression and mobilization has on drosophila brain development and on cerebral organoid development. Drosophila and cerebral organoids will be treated with nucleoside reverse transcriptase inhibitors (nrtis) to prevent RTE activity. Single-cell RNA sequencing will reveal the cell-type specific differences between control models and models treated with nrtis. In my second aim, i will investigate the mechanism by which unrestricted RTE activity can cause microcephaly. Preliminary data shows increased nspc death in a drosophila model of microcephaly. I will determine whether this is true in multiple other microcephaly models and determine if DNA damage caused by RTE activation in drosophila microcephaly models leads to the nspc death observed. The proposed research will illuminate the role of RTE activity during neurodevelopment. Importantly, IT will also provide crucial information to inform whether inhibition of rtes during development is a viable therapeutic for microcephaly and other neurodevelopmental diseases that are caused by rtes, thus prompting future pre-clinical studies.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $76,756 | |
| Amendment | $4,784 | |
| Amendment | $4,784 | |
| Amendment | $69,500 | |
| Amendment | $69,500 | |
| Amendment | $0 | |
| Amendment | $69,500 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Original award | $69,500 |
Quick answers
Who received award F32HD114499?
F32HD114499 was awarded to Cleveland Clinic Lerner College Of Medicine Of Case Western Reserve University by National Institute of Child Health and Human Development (National Institutes of Health) on August 15, 2024.
How much is award F32HD114499 worth?
$364,324 has been obligated on F32HD114499.
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