Saturday, November 23, 2024 11/23/2024

Molecular mechanisms of autophagosome biogenesis

Award Number: R01GM092740
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Abstract The catabolic process known as autophagy is essential for the maintenance of cellular health and the removal of cytotoxins, such as aberrant macromolecules, damaged organelles, and invasive bacteria. The hallmark of autophagy is de novo formation of the double-membrane vesicle called autophagosome. The process begins with assembling the precursor membrane phagophore adjacent to the endoplasmic reticulum (ER), followed by its expansion into a cup-like shape around a non-selective portion of the cytoplasm or a selected cytotoxin. During the expansion, the edges of the phagophore remain associated with the ER and at the last moment, the edges merge, resulting in the closure of the cup, thereby producing a complete autophagosome. The contribution to cellular homeostasis by autophagy hinges on the fact that the phagophore can engulf degradation substrates. For the phagophore to achieve this remarkable task, it must expand. We and others have made progress toward the goal of understanding the molecular mechanism of phagophore expansion by determining the function of ATG2, the largest protein in the group of autophagy- related proteins. We have worked on human ATG2A and demonstrated that this protein is a rod-shaped membrane tether that can transfer lipids between membranes. Our current working model is that ATG2 transports lipids from the ER to the phagophore by tethering them. The transported lipids would then serve as the building blocks the phagophore built around the substrates. This new proposal aims to build on this model and gain further mechanistic insights into this enigmatic process. In Aim 1, we will extend our study of ATG2 to determine its structure. The goal is to explain how ATG2 transports lipids between membranes. In Aim 2, we will focus on ATG9, the integral membrane protein of autophagy that has been known as an ATG2 interactor. Through structural and biochemical characterizations, we aim to elucidate the function of this protein and gain new insights into phagophore expansion. In Aim 3, we will characterize the interaction between ATG2 and ATG9. The goal is to determine how these two proteins interact with each other at the structural level and explore the significance of the interaction for ATG2-mediated lipid transfer and phagophore expansion. Results from these studies will vertically advance our understanding of autophagosome biogenesis at the molecular level.


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: 2023 ( Subtotal = $610,539 )
2023	2023	SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE	3525 JOHN HOPKINS CT	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	000	14	3/21/2023	NON-COMPETING CONTINUATION	$480,194
2023	2023	SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE	3525 JOHN HOPKINS CT	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	001	14	9/7/2023	SUPPLEMENT FOR EXPANSION	$130,345
														Subtotal = $610,539

Issue Date FY: 2022 ( Subtotal = $682,578 )
2022	2022	SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE	3525 JOHN HOPKINS CT	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	004	13	7/27/2022	NON-COMPETING CONTINUATION	$48,021
2022	2022	SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE	3525 JOHN HOPKINS CT	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	002	13	3/4/2022	NON-COMPETING CONTINUATION	$432,173
2022	2022	SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE	3525 JOHN HOPKINS CT	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	003	13	6/28/2022	SUPPLEMENT FOR EXPANSION	$197,230
2022	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	11	1/27/2022	NON-COMPETING CONTINUATION	-$63,092
2022	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	005	11	8/1/2022	NON-COMPETING CONTINUATION	-$10,760
2022	2021	SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE	3525 JOHN HOPKINS CT	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	006	12	8/1/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$10,760
2022	2021	SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE	3525 JOHN HOPKINS CT	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	001	12	1/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$68,246
														Subtotal = $682,578

Issue Date FY: 2021 ( Subtotal = $443,929 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	11	3/25/2021	NON-COMPETING CONTINUATION	$443,929
2021	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	9	2/7/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $443,929

Issue Date FY: 2020 ( Subtotal = $443,929 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	10	3/4/2020	COMPETING CONTINUATION	$443,929
														Subtotal = $443,929

Issue Date FY: 2019 ( Subtotal = $467,423 )
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	9	3/4/2019	NON-COMPETING CONTINUATION	$467,423
														Subtotal = $467,423

Issue Date FY: 2018 ( Subtotal = $467,423 )
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	8	3/9/2018	NON-COMPETING CONTINUATION	$420,680
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	8	6/11/2018	NON-COMPETING CONTINUATION	$46,743
														Subtotal = $467,423

Issue Date FY: 2017 ( Subtotal = $467,423 )
2017	2017	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	7	3/1/2017	NON-COMPETING CONTINUATION	$420,680
2017	2017	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	002	7	8/15/2017	NON-COMPETING CONTINUATION	$46,743
2017	2015	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	5	10/26/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $467,423

Issue Date FY: 2016 ( Subtotal = $467,423 )
2016	2016	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	6	7/1/2016	COMPETING CONTINUATION	$467,423
2016	2015	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	5	6/28/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $467,423

Issue Date FY: 2015 ( Subtotal = $379,000 )
2015	2015	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	5	2/10/2015	NON-COMPETING CONTINUATION	$37,900
2015	2015	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	5	11/18/2014	NON-COMPETING CONTINUATION	$341,100
														Subtotal = $379,000

Issue Date FY: 2014 ( Subtotal = $379,000 )
2014	2014	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	4	3/20/2014	NON-COMPETING CONTINUATION	$37,900
2014	2014	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	4	11/27/2013	NON-COMPETING CONTINUATION	$341,100
														Subtotal = $379,000

Issue Date FY: 2013 ( Subtotal = $365,735 )
2013	2013	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	3	6/17/2013	NON-COMPETING CONTINUATION	$24,635
2013	2013	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	3	11/23/2012	NON-COMPETING CONTINUATION	$341,100
														Subtotal = $365,735

Issue Date FY: 2012 ( Subtotal = $379,000 )
2012	2012	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	2	3/26/2012	NON-COMPETING CONTINUATION	$37,900
2012	2012	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	2	11/25/2011	NON-COMPETING CONTINUATION	$341,100
														Subtotal = $379,000

Issue Date FY: 2011 ( Subtotal = $379,000 )
2011	2011	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	11/26/2010	NEW	$379,000
														Subtotal = $379,000

Grand Total All Awards = $5,932,402

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular mechanisms of autophagosome biogenesis

Award Number: R01GM092740

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer