Wednesday, February 18, 2026 2/18/2026

Disease consequences and regulation of autophagy-independent ATG3 activity

Award Number: F31GM149144
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/16/2024
PERIOD OF PERFORMANCE END DATE: 07/15/2026

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Disease consequences and regulation of autophagy-independent ATG3 activity - Project Summary/Abstract Macroautophagy is a degradative cellular process that is upregulated in response to stress. Dysregulation of autophagy is broadly associated with several diseases including cancer, aging, and neurodegeneration. However, since this process is essential for mammalian development, diseases affecting core autophagy genes are very rare. For example, ATG3 is a core autophagy gene that is crucial for the formation of the autophagosome and there are no known disease-causing mutations within this gene. Interestingly, there is a patient with an undiagnosed severe neurodevelopmental disease found to have a point mutation in a single allele of the ATG3 gene. Intriguingly, ATG3 has been implicated in other conjugations thought to be independent of autophagy. These other conjugations regulate mitochondria and endolysosomal trafficking, both of which have significant roles in neurologic disease. My thesis work has largely focused on the patient mutation and its effect on autophagy, but my preliminary data indicates that all ATG3 activities appear to be disrupted in patient cells. Therefore, I propose to develop tools to further understand the cell biological consequences of these non-canonical ATG3 activities and use these tools to understand the effect of the patient mutation beyond autophagy. This project is designed to provide training for a successful future career in independent research. The findings from this project will improve the understanding of complex cellular processes and how they can result in disease. This proposal focuses on two aims: Aim One – Determine the impact of a patient mutation on lipidation- independent activities of ATG3; Aim Two – Determine if lipidation-independent ATG3 activity is dependent on membrane binding. Aim One will use microscopy techniques I developed in patient cells and a knockout- rescue strategy in gene-edited cells to directly evaluate the impact of the mutation on the formation and downstream consequences of these autophagy-independent complexes. Aim Two will capitalize on the techniques established in Aim One and biochemical experiments routinely performed in our lab to investigate potential mechanisms by which these autophagy-independent ATG3 complexes are regulated and function. The work in this proposal detailing the effect of this ATG3 mutation has the potential to describe the first severe disease-producing allele of ATG3. Additionally, this work aims to distinguish and characterize previously inseparable ATG3 functions, leading to a new understanding of both foundational biological processes and their downstream clinical relevance.


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 = $32,769 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	3	1/15/2026	NON-COMPETING CONTINUATION	$32,769
														Subtotal = $32,769

Issue Date FY: 2025 ( Subtotal = $48,974 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	2	1/14/2025	NON-COMPETING CONTINUATION	$48,974
														Subtotal = $48,974

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	001	1	1/10/2024	NEW	$0
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	003	1	6/11/2024	NEW	$1,280
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	002	1	1/10/2024	NEW	$0
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	1	1/10/2024	NEW	$47,694
														Subtotal = $48,974

Grand Total All Awards = $130,717

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Disease consequences and regulation of autophagy-independent ATG3 activity

Award Number: F31GM149144

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/16/2024

PERIOD OF PERFORMANCE END DATE: 07/15/2026

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