# Regulation of autophagy during animal development

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $684,810

## Abstract

PROJECT SUMMARY
Autophagy is used by all cells to deliver cytoplasmic material to the lysosome for degradation.
Significantly, autophagy has been implicated in several human diseases, including inflammatory
disorders, cancer and neurodegeneration. Most of what we know about the regulation of
autophagy is based on pioneering studies in yeast that defined the core autophagy machinery,
but recent studies in animals have revealed that autophagy can possess different regulatory
mechanisms in distinct cell types. Our research program aims to understand how autophagy is
regulated under physiological conditions, and here we investigate developmentally programmed
autophagy in the Drosophila intestine. This system possesses several advantages for these
studies, including robust genetic, genomic and cell biological tools that enable sophisticated
cellular analyses at single cell resolution. We have focused on studying autophagy in midgut
enterocyte cells of the intestine as a model. Developing midgut cells require autophagy for
proper cell death and degradation. Importantly, these cells are the only existing model to study
how distinct cargoes, including endoplasmic reticulum (ER) and mitochondria, are selectively
cleared by autophagy within a single cell in a physiological context. Our future research program
contains 4 projects that will address key questions in the autophagy field, with a specific focus
on how specific organelle cargoes are distinguished and selected for autophagy. What genes
regulate mitochondrial clearance by autophagy? What genes are required for clearance of
endoplasmic reticulum by autophagy? Are mitochondrial and ER cargoes differentially selected
for autophagic clearance within a single cell during development? What genes and mechanisms
control endosome-dependent and Atg gene-independent pathway for the clearance of ER?
These proposed studies will address a critical gap in our knowledge about the cell context-
specific mechanisms that regulate autophagy and cargo recruitment within a developing animal.
Given the strong conservation of autophagy mechanisms between Drosophila and mammals,
we expect that what we discover will provide insight into the diversity of mechanisms that control
autophagy in humans, and how alterations in autophagy in different cell contexts may lead to
disease. Furthermore, an understanding of the diversity of mechanisms that control autophagy
in animals is essential knowledge for the design of rationale strategies to target autophagy for
disease therapies.

## Key facts

- **NIH application ID:** 10764966
- **Project number:** 2R35GM131689-06
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Eric H Baehrecke
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $684,810
- **Award type:** 2
- **Project period:** 2019-04-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764966

## Citation

> US National Institutes of Health, RePORTER application 10764966, Regulation of autophagy during animal development (2R35GM131689-06). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10764966. Licensed CC0.

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