Dysregulating brain transposable elements to study stress-induced social behaviors and gene expression
Active Project Grant Awarded Last action
- Award ID
- F31MH143414
- Recipient
-
Virginia Commonwealth University UEI MLQFL4JSSAA9
- Awarding agency
-
National Institute of Mental Health
National Institutes of Health, Department of Health and Human Services
- Obligated
- $91,060
Award facts
- Assistance listing
- 93.242 Mental Health Research Grants
- Completion date 0% complete
- Originally
- Place of performance
- Richmond, VA 23298, USA
Award details come from USAspending.gov.
Description
- Abstract
- This proposal aims to elucidate a potential neurobiological mechanism of stress-induced social behavior deficits. Chronic stress is well-known to contribute to neuropsychiatric disorders such as major depressive disorder and post-traumatic stress disorder, and social dysfunction is often cited by patients as a major quality of life problem. Based on previous work from the lab, transposable element (TE) dysregulation has been identified as a driver of social behavior deficits in stress- naïve mice. TES are known to be silenced in the genome by krab zinc finger protein (KZFP) transcription factors, which collectively bind the transcriptionally repressive cofactor TRIM28. Using novel synthetic TRIM28 variants delivered into the medial prefrontal cortex (MPFC) of male and female mice, this study will probe the connection between chronic stress, MPFC TE stability, and social behavior. The synthetic TRIM28 variants, TRIM28WT and TRIM28VPR, exert opposing forms of transcriptional control, with TRIM28WT acting as a gene repressor and TRIM28VPR as an activator. Aim 1 seeks to determine the behavioral outcomes of applying synthetic TRIM28 variants to mice who have undergone chronic social stress, thereby providing training in the application of translationally relevant chronic stress paradigms. Restabilizing TES via TRIM28WT is predicted to reverse stress-induced social behavior deficits. Aim 2 seeks to characterize the MPFC transcriptional correlates of these behaviors, in terms of both canonical genes and TES, using bulk RNA sequencing of microdissected MPFC tissue. Moreover, aim 2 will relate these gene transcriptional changes to known changes induced by chronic social stress in the absence of TRIM28 manipulations. This will clarify the gene and TE transcriptional responses to chronic stress and will provide training in the analysis of complex bioinformatic data. Collectively, this project aims to understand the role of TE stability in the MPFC in stress-induced social behavior deficits, ideally culminating in a novel approach to address the GAP in quality of life for people with chronic stress associated neuropsychiatric disorders.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $45,530 | |
| Amendment | $0 | |
| Original award | $45,530 |
Quick answers
Who received award F31MH143414?
F31MH143414 was awarded to Virginia Commonwealth University by National Institute of Mental Health (National Institutes of Health) on December 10, 2026.
How much is award F31MH143414 worth?
$91,060 has been obligated on F31MH143414.
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