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The role of cell interactions in shaping development

Award Number: R35GM118081
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: 05/01/2016
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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The role of cell interactions in shaping development - PROJECT SUMMARY Interactions between cells direct many aspects of embryonic development. The long-term goal of our research program is to learn how cell interactions determine the shape, organization, and function of developing cells, tissues, and organs. Using C. elegans as an in vivo model where genetic analysis, live imaging and cell biology can be combined, we have developed several simple experimental systems to investigate how cell interactions regulate conserved morphogenetic events. The specific goals of this proposal are to use these model systems to fill key gaps in understanding how cells develop polarity, how small tubes form, and how niche cell interactions regulate germ cell biology. In one project, we are investigating how cell contact induces apicobasal polarity. This project addresses two outstanding questions – how cell contacts induce the PAR protein asymmetries that polarize cells, and how PAR proteins elaborate other intracellular asymmetries. We previously discovered that E-cadherin signals to induce polarity by recruiting the RhoGAP PAC-1, which triggers PAR protein asymmetries. We will extend these findings by uncovering new molecular links connecting PAC-1 to the E-cadherin cytoplasmic tail, by identifying additional signaling pathways that contribute to polarization, and by investigating how the PAR protein aPKC induces the formation of epithelial junctions. In a second project, we are investigating how small tubes develop. Small tubes such as capillaries can form in the cytoplasm of a cell when vesicles are targeted to an invading apical domain. It is unclear how vesicles are targeted to this site to form intracellular tubes. We are addressing this question by determining how the excretory cell forms an intracellular tube. We found that PAR proteins localize the exocyst vesicle- tethering complex to direct vesicle fusion events to the invading apical domain, and will extend these findings by investigating how PAR proteins recruit the exocyst and how the initial site for tube formation is specified. In a final project, we are determining how niche cell interactions influence germ cell development. Niche cells wrap membrane extensions around germ cells and stem cells but the significance of these interactions is poorly understood. We discovered that primordial germ cells (PGCs) extend large protrusions that are wrapped and cannibalized by intestinal cells, eliminating most PGC mitochondria. We will determine the importance of PGC lobe cannibalism, testing the hypothesis that it helps ensure the health of germline mitochondria. Together, our findings will reveal new, basic insights into how cell interactions guide critical developmental events, providing a foundation for understanding the contribution of cell interactions in human development and disease.


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 = $490,282 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	002	11	4/28/2025	NON-COMPETING CONTINUATION	$490,282
2025	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	10	11/6/2024	NON-COMPETING CONTINUATION	$0
2025	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	8	1/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $490,282

Issue Date FY: 2024 ( Subtotal = $461,980 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	004	10	7/17/2024	NON-COMPETING CONTINUATION	$49,162
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	003	10	4/10/2024	NON-COMPETING CONTINUATION	$442,466
2024	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	8	2/28/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	8	2/28/2024	NON-COMPETING CONTINUATION	-$369,952
2024	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	002	9	2/28/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$340,304
														Subtotal = $461,980

Issue Date FY: 2023 ( Subtotal = $718,595 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	002	8	5/22/2023	SUPPLEMENT FOR EXPANSION	$85,268
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	8	4/6/2023	NON-COMPETING CONTINUATION	$633,327
2023	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	5	11/23/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $718,595

Issue Date FY: 2022 ( Subtotal = $633,327 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	7	4/27/2022	NON-COMPETING CONTINUATION	$633,327
														Subtotal = $633,327

Issue Date FY: 2021 ( Subtotal = $633,327 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	002	6	9/5/2021	COMPETING CONTINUATION	$0
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	6	4/27/2021	COMPETING CONTINUATION	$633,327
2021	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	5	9/5/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $633,327

Issue Date FY: 2020 ( Subtotal = $591,894 )
2020	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	5	4/6/2020	NON-COMPETING CONTINUATION	$591,894
														Subtotal = $591,894

Issue Date FY: 2019 ( Subtotal = $619,882 )
2019	2019	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	4	6/14/2019	SUPPLEMENT FOR EXPANSION	$27,988
2019	2019	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	4	4/10/2019	NON-COMPETING CONTINUATION	$591,894
														Subtotal = $619,882

Issue Date FY: 2018 ( Subtotal = $591,894 )
2018	2018	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	3	4/24/2018	NON-COMPETING CONTINUATION	$591,894
														Subtotal = $591,894

Issue Date FY: 2017 ( Subtotal = $591,894 )
2017	2017	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	2	6/29/2017	NON-COMPETING CONTINUATION	$59,190
2017	2017	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	2	5/1/2017	NON-COMPETING CONTINUATION	$532,704
														Subtotal = $591,894

Issue Date FY: 2016 ( Subtotal = $507,395 )
2016	2016	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	1	4/12/2016	NEW	$507,395
														Subtotal = $507,395

Grand Total All Awards = $5,840,470

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The role of cell interactions in shaping development

Award Number: R35GM118081

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: 05/01/2016

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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