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Regulatory Strategies for the Control of Activity-Dependent Gene Expression in a Single Neuron Type

Award Number: F31NS137615
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 09/30/2026

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Regulatory Strategies for the Control of Activity-Dependent Gene Expression in a Single Neuron Type - Project Summary 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $15,832 )
2026	2026	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/28/2026	NON-COMPETING CONTINUATION	$15,832
														Subtotal = $15,832

Issue Date FY: 2025 ( Subtotal = $35,887 )
2025	2025	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/15/2025	NON-COMPETING CONTINUATION	$35,323
2025	2025	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	8/11/2025	NON-COMPETING CONTINUATION	$564
														Subtotal = $35,887

Issue Date FY: 2024 ( Subtotal = $35,233 )
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	4/15/2024	NEW	$0
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/15/2024	NEW	$33,953
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	5/7/2024	NEW	$1,280
														Subtotal = $35,233

Grand Total All Awards = $86,952

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Regulatory Strategies for the Control of Activity-Dependent Gene Expression in a Single Neuron Type

Award Number: F31NS137615

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 09/30/2026

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