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Transcriptional regulation of post-embryonic neuronal maturation

Award Number: R00HD098371
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Transcriptional regulation of post-embryonic neuronal maturation - PROJECT SUMMARY/ABSTRACT During the complex and intricately-timed sequence of nervous system development and maturation, significant and persistent disruptions to the dynamic regulatory process through genetic and environmental risks can result in neurodevelopmental disorders. Neuroscience research has contributed much to our understanding of early neural development in the embryonic and perinatal periods including neuronal specification, neuronal migration, axonal guidance/outgrowth, and synaptogenesis. The period from early post-natal life to young adulthood is equally critical for proper development of the mature brain, as extensive structural and behavioral plasticity are observed during these periods. However, much less is known about the molecular regulatory mechanisms underlying neuronal maturation during post-natal development. In the first part of my post-doctoral work, I developed and optimized a method to isolate single neuron types for genomics profiling. Using this method, in combination with the genetic amenability of the C. elegans system, I will profile the transcriptome and chromatin accessibility of single neuron types throughout early post-natal development to young adulthood (Aim 1). In Aim 2, using the profiling data from Aim 1 as an entry point, I will take a 2-pronged approach to identify novel regulators of neuronal maturation. First, I will co-develop and implement bioinformatics tools to extract common cis-regulatory motifs from developmentally regulated genes and predict candidate transcriptional regulators. Second, using validated developmentally-regulated gene reporters in Aim 1, I will conduct unbiased forward genetic screens to identify novel regulators of neuronal maturation. In Aim 3, I will use advanced neurotechnology tools to examine the role of environmental stimuli (sensory-induced neuron activity) on neuronal maturation. First, I will examine how acute and chronic inhibition of activity in target neurons, during different developmental windows, affects single-neuron developmental transcriptomes and chromatin accessibility. In addition, the interaction between pathways regulating neuronal maturation through environmentally-induced activity versus intrinsic genetic mechanisms will be examined using approaches as in Aim 2. The proposed research will increase our understanding of the genetic and environmental regulatory mechanisms underlying normal post-natal neurodevelopment, improve our understanding of the etiology of neurodevelopmental disorders, and reveal novel therapeutic targets. The training phase of the award, conducted in the laboratory of Dr. Oliver Hobert and under the co- mentorship of Dr. Harmen Bussemaker and Dr. Stavros Lomvardas at Columbia University, outlines a comprehensive plan for the acquisition of technical and professional skills that will enable my transition to an independent research position. The successful completion of this project will provide a platform for future experiments aimed at understanding gene-environment interplay in the transcriptional regulation of nervous system development and function. .


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: 2025 ( Subtotal = -$21,953 )
2025	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	5	12/29/2024	NON-COMPETING CONTINUATION	-$21,953
														Subtotal = -$21,953

Issue Date FY: 2023 ( Subtotal = $249,000 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	5	8/21/2023	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2022 ( Subtotal = $405,083 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Child Health and Human Development Extramural Research	002	4	8/30/2022	SUPPLEMENT FOR EXPANSION	$71,767
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Child Health and Human Development Extramural Research	003	4	8/31/2022	SUPPLEMENT FOR EXPANSION	$84,315
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Child Health and Human Development Extramural Research	001	4	8/22/2022	NON-COMPETING CONTINUATION	$248,201
2022	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	3	5/20/2022	EXTENSION WITH OR WITHOUT FUNDS	$800
														Subtotal = $405,083

Issue Date FY: 2021 ( Subtotal = $249,000 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	3	9/1/2021	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $881,130

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Transcriptional regulation of post-embryonic neuronal maturation

Award Number: R00HD098371

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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