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Comparative systems biology defines regulatory mechanisms in whole-body regeneration

Award Number: R35GM138061
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: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2030

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Comparative systems biology defines regulatory mechanisms in whole-body regeneration - Project Summary Certain animals, from Hydra to salamanders, can regenerate extensive portions of their bodies through a process that involves intricate coordination of diverse cell types. Despite major advances from studies of highly regenerative models, critical knowledge gaps remain in understanding how regenerative programs are switched on or off, how preexisting body structures integrate with newly formed tissues, and what determines the vast differences in regenerative capacities across animals. In this proposal, building on our prior progress, we will explore these questions by comparing species that display markedly different regenerative capacities, from the planarian Schmidtea mediterranea with its extreme regenerative ability to closely related planarian species that regenerate poorly. We will also use our newly developed transgenic and live-imaging tools to capture real-time morphodynamics in the marine flatworm Macrostomum lignano and dissect the morphogenetic tissue transformations during regeneration. Additionally, we will study the acoel worm Convolutriloba longifissura, which “farms” its photosynthetic algal symbionts to fuel regeneration. Across these systems, we will identify “regeneration suppressors” that limit regeneration during homeostasis, unravel the roles and regulation of cell turnover in controlling regeneration competence, determine whether regeneration follows an optimal morphogenetic “solution”, and uncover novel mechanisms that can support stem cell proliferation through solar power. Together, our plan integrates functional genomic analysis, new genetic tools, live-imaging, single-cell multi-omic sequencing, and mathematical modeling to illuminate how regeneration is initiated, executed, and refined. By clarifying the core design principles of regeneration across diverse organisms, we aim to advance the fundamental biological basis of regenerative medicine and inform future strategies for enhancing tissue repair while minimizing the risk of uncontrolled growth.


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 = $523,085 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	6	2/11/2026	COMPETING CONTINUATION	$523,085
2026	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	5	2/9/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $523,085

Issue Date FY: 2024 ( Subtotal = $393,296 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	5	6/24/2024	NON-COMPETING CONTINUATION	$393,296
														Subtotal = $393,296

Issue Date FY: 2023 ( Subtotal = $393,296 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	4	9/8/2023	NON-COMPETING CONTINUATION	$393,296
														Subtotal = $393,296

Issue Date FY: 2022 ( Subtotal = $393,296 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	3	6/30/2022	NON-COMPETING CONTINUATION	$393,296
														Subtotal = $393,296

Issue Date FY: 2021 ( Subtotal = $393,296 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	2	6/18/2021	NON-COMPETING CONTINUATION	$393,296
														Subtotal = $393,296

Issue Date FY: 2020 ( Subtotal = $393,296 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	1	8/27/2020	NEW	$393,296
														Subtotal = $393,296

Grand Total All Awards = $2,489,565

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Comparative systems biology defines regulatory mechanisms in whole-body regeneration

Award Number: R35GM138061

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: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2030

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