Regulatory strategies for the control of activity-dependent gene expression in a single neuron type
Ended Project Grant Awarded Last action
- Award ID
- F31NS137615
- Recipient
-
Brandeis University UEI MXLZGAMFEKN5
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $260,647
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date
- Place of performance
- Waltham, MA 02453, USA
Award details come from USAspending.gov.
Description
- Abstract
- A neuron's activity history is precisely encoded in its gene expression profile. This molecular encoding is achieved via transcriptional regulatory programs specific to distinct features of activity patterns. In particular, an activating stimulus evokes unique, temporally segregated waves of transcription as a function of its duration. The regulatory mechanisms which orchestrate the transduction of stimuli duration into temporal waves of transcription have been described in heterogenous populations of neuronal cell types. However, whether similar or distinct mechanisms operate to translate activity patterns into specific expression programs in defined neuronal subtypes in vivo is unknown. We have established AFD, a pair of sensory neurons in c. Elegans, as a cellular model in which to describe the regulatory pathways that transduce neuronal activity into gene expression changes. Via AFD specific RNA-SEQ, we have shown that the duration of temperature experience is encoded in AFD by temporal waves of gene expression reflecting similar waves described in more complex organisms. These temporally regulated gene expression changes are critical for modulating AFD functions. Preliminarily, bioinformatics analyses and experimental manipulations suggest that the creb transcription factor together with the SPR-4/rest repressor shape the temporal kinetics of temperature- induced upregulation in a subset of genes. The goal of this proposal is to provide a systematic mechanistic description of the molecular pathways by which the duration of temperature experience is encoded in the molecular profile of AFD. Experiments proposed in aim 1 will employ a multifaceted approach including bioinformatics analyses, experimental deletions, and AFD-specific atac-SEQ to identify CIS-acting regulatory motifs which direct activity-dependent transcription in AFD as a function of stimulus duration, and to determine their role in the epigenetic control of gene expression. In aim 2, these motifs will be linked to their cognate transcription factors (TFS), and the mechanisms by which antagonism between activator and repressor TFS shape gene expression programs will be investigated. Together, results from this work will provide a comprehensive description of how a defined environmental experience is precisely translated into gene expression programs in an individual neuron type in vivo to modulate neuronal properties.
Transactions
| Action | Obligated | Date |
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| Amendment | $15,832 | |
| Amendment | $564 | |
| Amendment | $35,323 | |
| Amendment | $35,323 | |
| Amendment | $1,280 | |
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| Amendment | $33,953 | |
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| Amendment | $0 | |
| Amendment | $33,953 | |
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| Amendment | $33,953 | |
| Amendment | $33,953 | |
| Original award | $0 |
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Quick answers
Who received award F31NS137615?
F31NS137615 was awarded to Brandeis University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on December 1, 2024.
How much is award F31NS137615 worth?
$260,647 has been obligated on F31NS137615.
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