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Regulation of autophagy during animal development

Award Number: R35GM131689
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: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Regulation of autophagy during animal development - PROJECT SUMMARY Autophagy is used by all cells to deliver cytoplasmic material to the lysosome for degradation. Significantly, autophagy has been implicated in several human diseases, including inflammatory disorders, cancer and neurodegeneration. Most of what we know about the regulation of autophagy is based on pioneering studies in yeast that defined the core autophagy machinery, but recent studies in animals have revealed that autophagy can possess different regulatory mechanisms in distinct cell types. Our research program aims to understand how autophagy is regulated under physiological conditions, and here we investigate developmentally programmed autophagy in the Drosophila intestine. This system possesses several advantages for these studies, including robust genetic, genomic and cell biological tools that enable sophisticated cellular analyses at single cell resolution. We have focused on studying autophagy in midgut enterocyte cells of the intestine as a model. Developing midgut cells require autophagy for proper cell death and degradation. Importantly, these cells are the only existing model to study how distinct cargoes, including endoplasmic reticulum (ER) and mitochondria, are selectively cleared by autophagy within a single cell in a physiological context. Our future research program contains 4 projects that will address key questions in the autophagy field, with a specific focus on how specific organelle cargoes are distinguished and selected for autophagy. What genes regulate mitochondrial clearance by autophagy? What genes are required for clearance of endoplasmic reticulum by autophagy? Are mitochondrial and ER cargoes differentially selected for autophagic clearance within a single cell during development? What genes and mechanisms control endosome-dependent and Atg gene-independent pathway for the clearance of ER? These proposed studies will address a critical gap in our knowledge about the cell context- specific mechanisms that regulate autophagy and cargo recruitment within a developing animal. Given the strong conservation of autophagy mechanisms between Drosophila and mammals, we expect that what we discover will provide insight into the diversity of mechanisms that control autophagy in humans, and how alterations in autophagy in different cell contexts may lead to disease. Furthermore, an understanding of the diversity of mechanisms that control autophagy in animals is essential knowledge for the design of rationale strategies to target autophagy for disease therapies.


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 = $684,810 )
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	8	2/9/2026	NON-COMPETING CONTINUATION	$684,810
														Subtotal = $684,810

Issue Date FY: 2025 ( Subtotal = $684,810 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	002	7	2/21/2025	NON-COMPETING CONTINUATION	$616,330
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	004	7	8/15/2025	NON-COMPETING CONTINUATION	$0
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	003	7	8/8/2025	NON-COMPETING CONTINUATION	$68,480
2025	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	6	11/25/2024	COMPETING CONTINUATION	$0
2025	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	5	2/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $684,810

Issue Date FY: 2024 ( Subtotal = $684,810 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	6	2/2/2024	COMPETING CONTINUATION	$684,810
														Subtotal = $684,810

Issue Date FY: 2023 ( Subtotal = $633,205 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	5	3/3/2023	NON-COMPETING CONTINUATION	$633,205
														Subtotal = $633,205

Issue Date FY: 2022 ( Subtotal = $633,205 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	4	3/15/2022	NON-COMPETING CONTINUATION	$569,883
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	4	7/21/2022	NON-COMPETING CONTINUATION	$63,322
														Subtotal = $633,205

Issue Date FY: 2021 ( Subtotal = $633,205 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	3	3/9/2021	NON-COMPETING CONTINUATION	$633,205
														Subtotal = $633,205

Issue Date FY: 2020 ( Subtotal = $633,205 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	2	3/30/2020	NON-COMPETING CONTINUATION	$633,205
														Subtotal = $633,205

Issue Date FY: 2019 ( Subtotal = $312,111 )
2019	2019	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	1	3/15/2019	NEW	$312,111
														Subtotal = $312,111

Grand Total All Awards = $4,899,361

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Regulation of autophagy during animal development

Award Number: R35GM131689

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: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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