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MECHANISMS OF ORGANELLE BIOGENESIS AT THE ENDOPLASMIC RETICULUM SUBDOMAINS

Award Number: R35GM147189
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: 08/15/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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MECHANISMS OF ORGANELLE BIOGENESIS AT THE ENDOPLASMIC RETICULUM SUBDOMAINS - PROJECT SUMMARY Intracellular membrane-bound organelles are a hallmark of all eukaryotic cells. Understanding how cells generate different organelles remains one of the central problems in cell biology. Some organelles, like the endoplasmic reticulum (ER) and mitochondria, are self-generating whereas other organelles can be generated de novo. The ER plays a central role in organelle biogenesis. Even though the ER is a single continuous membrane that extends from the outer nuclear envelope into the periphery of the cell, there are discrete regions in the ER membrane called ER subdomains. Nascent peroxisomes and lipid droplets (LDs) form at specialized ER subdomains. Remarkably, little is known about these ER subdomains and their role in regulating organelle biogenesis. The goal of our research is to determine the mechanisms of peroxisome and LD biogenesis by detailed characterization of the discrete ER subdomains using S. cerevisiae and mammalian cell culture. Previously, we identified a family of reticulon-like ER membrane tubulating proteins, Pex30 in yeasts and multiple C2 domains containing transmembrane proteins, MCTP1 and MCTP2, in higher eukaryotes. We demonstrated that both Pex30 and MCTPs are localized at discrete ER subdomains where nascent pre-peroxisomal vesicles and LDs are formed. Based on these findings, we proposed to identify the proteins and lipids enriched at the specialized ER subdomains using unbiased as well as candidate-based approaches. We will then test the effects of modulating the functions of candidate proteins and lipids on the formation, abundance, morphology, and distribution of peroxisomes and LDs. Investigating the mechanistic details of peroxisomes and LDs biogenesis from these ER subdomains is not only important for understanding basic principles of cell biology but also has critical medical implications. Several life-threatening neurological disorders including Zellweger syndrome associated with peroxisomal defects and metabolic disorders such as type 2 diabetes and fatty liver disease caused due to LD defects have no cure. Determining the mechanisms of organelle biogenesis will have implications in understanding the pathophysiology of these disorders and provide us hints for potential therapeutic targets.


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 = $376,892 )
2025	2025	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	4	6/23/2025	NON-COMPETING CONTINUATION	$376,892
														Subtotal = $376,892

Issue Date FY: 2024 ( Subtotal = $377,002 )
2024	2024	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	3	6/28/2024	NON-COMPETING CONTINUATION	$377,002
														Subtotal = $377,002

Issue Date FY: 2023 ( Subtotal = $620,643 )
2023	2023	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	001	2	9/14/2023	SUPPLEMENT FOR EXPANSION	$245,524
2023	2023	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	2	6/16/2023	NON-COMPETING CONTINUATION	$375,119
														Subtotal = $620,643

Issue Date FY: 2022 ( Subtotal = $371,302 )
2022	2022	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Biomedical Research and Research Training	000	1	8/15/2022	NEW	$371,302
														Subtotal = $371,302

Grand Total All Awards = $1,745,839

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MECHANISMS OF ORGANELLE BIOGENESIS AT THE ENDOPLASMIC RETICULUM SUBDOMAINS

Award Number: R35GM147189

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: 08/15/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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