# Decode Mitochondrial Morphology Dynamics to Predict Cell Fate Decisions

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $1,422,000

## Abstract

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.

## Key facts

- **NIH application ID:** 10473200
- **Project number:** 1DP2GM150022-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Johannes Schoeneberg
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,422,000
- **Award type:** 1
- **Project period:** 2022-09-08 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10473200

## Citation

> US National Institutes of Health, RePORTER application 10473200, Decode Mitochondrial Morphology Dynamics to Predict Cell Fate Decisions (1DP2GM150022-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10473200. Licensed CC0.

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