# Regulation of autophagy during animal development

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $633,205

## Abstract

ABSTRACT
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 in 2 cell types during development of Drosophila. 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 dying larval salivary gland cells and midgut enterocyte cells of the intestine as
models. Both salivary gland and midgut cells require autophagy for proper death and
degradation, but use entirely different mechanisms for the activation of autophagy. Salivary
gland autophagy is regulated by an ancient inflammatory signaling pathway that includes the
complement factor Mcr and the engulfment receptor Draper, but this pathway is not required for
autophagy in either fatbody cells following nutrient deprivation or midgut cells of the intestine
during development. By contrast, midgut cells of the intestine require a ubiquitin-dependent
autophagy program that interfaces with mitochondrial dynamics through the novel Vps13D
protein. Significantly, Vps13D is not required for autophagy in either fatbody or salivary gland
cells. Our future research program contains 4 projects that will address key questions in the
autophagy field. What is the role of inflammatory signaling in developmental autophagy? What
is the role of mitochondrial dynamics in autophagy? What is the role of ubiquitin in autophagy?
What is the role of previously undiscovered pathways in context-specific regulation of
autophagy? These proposed studies will address a critical gap in our knowledge about the cell
context-specific mechanisms that regulate autophagy within an 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:** 9894807
- **Project number:** 5R35GM131689-02
- **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:** 2020
- **Award amount:** $633,205
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894807

## Citation

> US National Institutes of Health, RePORTER application 9894807, Regulation of autophagy during animal development (5R35GM131689-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894807. Licensed CC0.

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