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Spatiotemporal Regulation of Developmental Pattern Formation

Award Number: R35GM152180
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Spatiotemporal Regulation of Developmental Pattern Formation - Project Summary/Abstract Despite their important role in birth defects and infant mortality, the 3-D and 4-D patterning processes that employ multiple signals to drive embryonic development and morphogenesis are not mechanistically understood. The long-term goal is to obtain a complete molecular description of 4-D pattern formation, using the simple yet relevant sea urchin larval skeleton as a model. The central objective in this application is to define a model that captures how the ectoderm expresses different patterning cues in different regions over space and time using systems biology approaches, to integrate that network with our spatiotemporal patterning cue reception network in the responsive skeletogenic cells, then use that network model to identify the underlying general principles for spatiotemporal deployment of and response to patterning instructions. The main hypothesis is that differential spatiotemporal expression of the set of signals that regulate skeleton formation is the central driver of embryonic pattern formation and is hard-wired into the ectodermal gene regulatory networks that regulate skeletal patterning, while the reception of those cues drives the spatiotemporal diversification of the skeleton-producing PMCs that in turn mediate morphogenesis. The expected outcomes are (i) a validated single-cell level set of interconnected spatiotemporal network models that define the presentation and reception of patterning cues between the relevant tissues and (ii) computational models that capture the overall network and that will allow rigorous analysis of the networks' functions. The research proposed in this application is innovative, in the applicant's opinion, because it utilizes novel analytical approaches and tools developed by the applicant's group, including a novel scRNA-seq data analysis algorithm, a new tool for automated 3-D mapping of skeletogenic cells from confocal image stacks, and polychrome skeletal labeling for post-hoc dynamics analysis. The proposed research is significant because will establish a highly resolved molecular map of a 4-D developmental process for skeletal patterning that will offer insight into the general principles that underlie complex pattern formation. Because of the conservation of many of the relevant patterning cues between sea urchin and human skeletons, this knowledge may ultimately lead to new approaches for the prevention or treatment of skeletal birth defects and new strategies for synthetic biomineral production.


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 = $371,250 )
2026	2026	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	3	1/15/2026	NON-COMPETING CONTINUATION	$371,250
														Subtotal = $371,250

Issue Date FY: 2025 ( Subtotal = $412,500 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	002	2	8/20/2025	NON-COMPETING CONTINUATION	$41,250
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	001	2	11/21/2024	NON-COMPETING CONTINUATION	$371,250
2025	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	1	11/5/2024	NEW	$0
														Subtotal = $412,500

Issue Date FY: 2024 ( Subtotal = $486,289 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	1	12/15/2023	NEW	$486,289
														Subtotal = $486,289

Grand Total All Awards = $1,270,039

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Spatiotemporal Regulation of Developmental Pattern Formation

Award Number: R35GM152180

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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