Thursday, November 21, 2024 11/21/2024

Notch signaling and germline-soma interactions in the Drosophila ovarian model

Award Number: R01GM072562
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Cell-cell communications among different cell groups, especially between the germline and somatic cells, are key to the development of a functional egg. At the center of germline-soma interactions in the Drosophila model lies the Notch pathway, which plays critical roles in a series of major events during oogenesis. Determining how Notch signaling regulates diverse cellular processes is fundamental to the understanding the regulation of oogenesis. On the other hand, the ovarian model offers an excellent platform to uncover novel regulatory mechanisms of this notoriously important pathway, with roles crucial in development, tissue homeostasis and pathogenesis of a multitude of human diseases. Despite many years of studies, there are still a significant number of unknowns in the field. For example, how Notch regulates growth in different developmental or pathological contexts, how the cell cycle machinery feeds back to modulate the Notch pathway and how environmental stresses impact the signaling output during development and tissue homeostasis. This proposal aims to address these questions using the genetically tractable Drosophila ovarian model system. The proposed studies are based on a series of previous findings and preliminary results. We have shown that Notch signaling induces cell differentiation by switching the follicle cells from the mitotic cycle to an endoreplication cycle, thus restricting cell proliferation. Interestingly, when combined with a loss of cell polarity gene lgl, we found that Notch promotes tissue growth in the follicle cell epithelium. We also found that String (Stg), a Cdc25 homolog, regulates the nuclear access of an active form of Notch, the Notch intracellular domain (NICD). Furthermore, we found that hyperactivation of Notch in follicle cells causes cell death and degeneration of germline cells through phagocytosis. These findings provide us the opportunity to further explore how germline and somatic development are coordinated during normal development and under environmental stresses, and to understand how Notch signaling regulates growth and survival in various biological and pathological conditions. The following three specific aims will be addressed using the ovarian model.1. To determine how Notch regulates tissue growth in different genetic backgrounds. 2. To determine how Cdc25/String regulates NICD nuclear access to impact Notch signaling. And 3. To determine how upregulated Notch activity in follicle cells induces germline cell death. Successful completion of these aims will lead to improved understanding of the diverse effects and regulatory mechanisms of Notch signaling during development and tissue homeostasis. The findings from the proposed studies will help designing new therapeutic strategies for diseases related to aberrant Notch signaling.


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: 2024 ( Subtotal = $581,196 )
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	000	17	5/17/2024	NON-COMPETING CONTINUATION	$315,180
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	001	17	5/20/2024	SUPPLEMENT FOR EXPANSION	$60,236
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	002	17	8/29/2024	SUPPLEMENT FOR EXPANSION	$205,780
														Subtotal = $581,196

Issue Date FY: 2023 ( Subtotal = $375,211 )
2023	2023	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	001	16	8/14/2023	NON-COMPETING CONTINUATION	$315,008
2023	2023	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	002	16	9/12/2023	SUPPLEMENT FOR EXPANSION	$60,203
2023	2020	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	000	14	11/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $375,211

Issue Date FY: 2022 ( Subtotal = $318,120 )
2022	2022	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	000	15	8/30/2022	COMPETING CONTINUATION	$318,120
														Subtotal = $318,120

Issue Date FY: 2020 ( Subtotal = $301,750 )
2020	2020	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	002	14	4/24/2020	NON-COMPETING CONTINUATION	$303,833
2020	2019	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	004	12	6/9/2020	NON-COMPETING CONTINUATION	-$54,727
2020	2019	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	001	13	1/27/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$249,031
2020	2019	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Biomedical Research and Research Training	005	13	6/9/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$210,973
2020	2019	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	12	1/27/2020	NON-COMPETING CONTINUATION	-$251,114
2020	2018	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	003	11	6/9/2020	NON-COMPETING CONTINUATION	-$156,246
														Subtotal = $301,750

Issue Date FY: 2019 ( Subtotal = $305,841 )
2019	2019	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	12	4/18/2019	NON-COMPETING CONTINUATION	$305,841
														Subtotal = $305,841

Issue Date FY: 2018 ( Subtotal = $304,328 )
2018	2018	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	002	11	4/25/2018	NON-COMPETING CONTINUATION	$304,328
2018	2017	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	10	12/2/2017	COMPETING CONTINUATION	$11,486
2018	2016	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	9	12/2/2017	EXTENSION WITH OR WITHOUT FUNDS	-$11,486
														Subtotal = $304,328

Issue Date FY: 2017 ( Subtotal = $304,445 )
2017	2017	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	10	7/20/2017	COMPETING CONTINUATION	$304,445
2017	2016	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	9	7/17/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $304,445

Issue Date FY: 2016 ( Subtotal = $280,781 )
2016	2016	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	9	2/9/2016	EXTENSION WITH OR WITHOUT FUNDS	$280,781
														Subtotal = $280,781

Issue Date FY: 2015 ( Subtotal = $442,799 )
2015	2015	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	8	6/16/2015	SUPPLEMENT FOR EXPANSION	$160,959
2015	2015	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	8	2/23/2015	NON-COMPETING CONTINUATION	$281,840
														Subtotal = $442,799

Issue Date FY: 2014 ( Subtotal = $282,332 )
2014	2014	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	7	2/26/2014	NON-COMPETING CONTINUATION	$282,332
														Subtotal = $282,332

Issue Date FY: 2013 ( Subtotal = $273,051 )
2013	2013	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	004	6	5/29/2013	COMPETING CONTINUATION	$273,051
2013	2012	FLORIDA STATE UNIVERSITY	A22001 UNIVERSITY CENTER	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	5	2/25/2013	SUPPLEMENT FOR EXPANSION	$0
2013	2012	FLORIDA STATE UNIVERSITY	A22001 UNIVERSITY CENTER	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	002	5	5/28/2013	SUPPLEMENT FOR EXPANSION	$0
2013	2010	FLORIDA STATE UNIVERSITY	A22001 UNIVERSITY CENTER	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	003	5	5/28/2013	NON-COMPETING CONTINUATION	$0
2013	2010	FLORIDA STATE UNIVERSITY	A22001 UNIVERSITY CENTER	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	5	2/25/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $273,051

Issue Date FY: 2012 ( Subtotal = $81,262 )
2012	2012	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	5	3/26/2012	SUPPLEMENT FOR EXPANSION	$81,262
2012	2010	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	5	3/26/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $81,262

Issue Date FY: 2010 ( Subtotal = $377,865 )
2010	2010	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Trans-NIH Recovery Act Research Support	000	4	1/15/2010	SUPPLEMENT FOR EXPANSION	$119,668
2010	2010	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	002	5	8/19/2010	NON-COMPETING CONTINUATION	$258,197
2010	2010	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Trans-NIH Recovery Act Research Support	001	4	3/19/2010	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $377,865

Issue Date FY: 2009 ( Subtotal = $287,400 )
2009	2009	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	4	7/28/2009	NON-COMPETING CONTINUATION	$246,571
2009	2009	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	4	8/25/2009	SUPPLEMENT FOR EXPANSION	$40,829
														Subtotal = $287,400

Issue Date FY: 2008 ( Subtotal = $246,862 ) (Continued on the next page)
Grand Total All Awards = $5,265,130

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Notch signaling and germline-soma interactions in the Drosophila ovarian model

Award Number: R01GM072562

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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