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Deciphering the Role of Endoplasmic Reticulum Structure and Function in Metabolic Regulation

Award Number: R35GM166424
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: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Deciphering the Role of Endoplasmic Reticulum Structure and Function in Metabolic Regulation - Project Summary / Abstract Cells optimize their functional capacity in response to extracellular signals to meet metabolic demands and maintain cellular and organism-level homeostasis. Endoplasmic reticulum (ER) is a central hub for protein folding, trafficking, lipid synthesis and secretion. ER also regulates the function of other organelles by exchanging ions and other hydrophobic molecules through inter- organelle contact sites. The structure of the ER is highly dynamic with specialized subdomains such as ER sheets, tubules, 3-way junctions and exit sites. ER exhibits complex architectural configuration related to cell’s functional capacity. However, whether and how different ER subdomains play a role in optimizing the functional capacity of the cell in response to metabolic demand is unclear. Moreover, the upstream signals that regulate ER shape dynamics are not known. In this proposal, we aim to use state-of-the-art metabolic flux approaches to investigate how the structural regulation of ER controls lipid and glucose fluxes in cells. Additionally, by using enhanced Focused Ion Beam Scanning Electron microscopy and super-resolution fluorescent microscopy, we will interrogate the ER’s architectural response to nutrient sensing and signaling pathways. Lastly, we will perform CRISPR-Cas9 screens, coupled with high-content imaging and deep learning-based analysis to discover novel regulators of ER shape and function. This work will provide novel insight into how organelle shape and dynamics regulate cellular function and health. It will introduce a new perspective to the field by incorporating subcellular architectural remodeling as a new layer of metabolic regulation.


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 = $414,394 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	119 CALIFORNIA HALL	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	1	7/28/2026	NEW	$414,394
														Subtotal = $414,394

Grand Total All Awards = $414,394

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Deciphering the Role of Endoplasmic Reticulum Structure and Function in Metabolic Regulation

Award Number: R35GM166424

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: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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