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Decode Mitochondrial Morphology Dynamics to Predict Cell Fate Decisions

Award Number: DP2GM150022
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: 09/08/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Decode Mitochondrial Morphology Dynamics to Predict Cell Fate Decisions - Project Summary/Abstract ABSTRACT Mitochondria not only provide 90% of the energy required for reading these very lines but they are also responsible for the correct differentiation of the cells lining your gut. The recent recognition that mitochondria play an active role in stem cell fate decisions has moved them from passive power plants to active centers of cell signaling. Our inability to automatically track mitochondria and link them to the fate of a cell is in stark contrast to the increasing relevance of this organelle in stem cell fate decisions and intestinal diseases such as Crohn’s disease and colorectal cancer. Mitochondria have always been too small and too fast for volumetric imaging and tracking. Our preliminary data show that a combination of recently developed lattice light-sheet microscopy and our in-house developed computational image processing pipeline can succeed in the four-dimensional tracking of the entire cellular mitochondrial network. Here we propose to 1) expand our prototype into a general tool that can track mitochondria in multiple cell types and network morphologies, to 2) elucidate the coupling between mitochondrial network morphology and cellular fate, and to 3) create a predictive model that links the mitochondrial network morphology to its underlying signaling drivers and to the fate decisions that are caused by different morphologies. We propose to use intestinal epithelial organoids and the differentiation of intestinal stem cells to paneth cells as a model system for a mitochondria-directed fate determination. This proposal will open a new window into mitochondrial biology that will translate to a large number of mitochondria-related diseases such as cancer and neurological disorders such as epilepsy, Parkinson’s disease, and Alzheimer’s disease.


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 = $0 )
2026	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	11/25/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $957,500 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	2	7/25/2025	EXTENSION WITH OR WITHOUT FUNDS	$957,500
														Subtotal = $957,500

Issue Date FY: 2022 ( Subtotal = $1,422,000 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	9/8/2022	NEW	$1,422,000
														Subtotal = $1,422,000

Grand Total All Awards = $2,379,500

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Decode Mitochondrial Morphology Dynamics to Predict Cell Fate Decisions

Award Number: DP2GM150022

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: 09/08/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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