Tuesday, November 18, 2025 11/18/2025

Mechanistic Understanding of Post-Translational Membrane Protein Targeting

Award Number: R35GM147522
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: 09/22/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Mechanistic Understanding of Post-Translational Membrane Protein Targeting - PROJECT SUMMARY / ABSTRACT The goal of the proposed study is to understand how cells accurately deliver and insert an essential class of membrane proteins known as tail-anchored proteins (TAs) into the endoplasmic reticulum (ER) membrane. TAs participate in a wide range of important cellular functions including vesicle transport, regulation of apoptosis, and protein quality control. While it is critical for their functions that newly synthesized TAs are localized to appropriate membranes, the details of how cells achieve this spatial organization is not clearly understood. To fill this current knowledge gap, the study proposed here aims to dissect the molecular mechanism of the `Guided Entry of Tail- anchored proteins' (GET) pathway, which guides newly synthesized TAs to the ER membrane. The overarching goal of this proposal is to visualize and understand the major molecular event of the GET pathway. This will be achieved by utilizing cryo-electron microscopy to obtain snapshots of key protein complexes in action, and by complementary protein-protein interaction and TA- insertion studies. More specifically, this study will investigate how the `pre-targeting complex' of the GET pathway captures and commits newly synthesized TAs to the ER-bound path, and once at the ER membrane how the Get1/2 insertase complex inserts TAs into the lipid-bilayer. Together, these multi-disciplinary approaches will enhance our understanding of how cells achieve accuracy and fidelity of TA-targeting, which is essential not only for TA functions but also for maintaining functional ER membrane. Furthermore, these studies will provide valuable insight into various human diseases such as diabetes, cancer and congenital heart disease that have been linked to defective GET pathway.


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 = $382,693 )
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	4	8/15/2025	NON-COMPETING CONTINUATION	$382,693
														Subtotal = $382,693

Issue Date FY: 2024 ( Subtotal = $383,022 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	3	8/28/2024	NON-COMPETING CONTINUATION	$383,022
														Subtotal = $383,022

Issue Date FY: 2023 ( Subtotal = $383,339 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	2	8/24/2023	NON-COMPETING CONTINUATION	$383,339
														Subtotal = $383,339

Issue Date FY: 2022 ( Subtotal = $377,993 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	1	9/22/2022	NEW	$377,993
														Subtotal = $377,993

Grand Total All Awards = $1,527,047

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Mechanistic Understanding of Post-Translational Membrane Protein Targeting

Award Number: R35GM147522

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: 09/22/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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