# Degradation of dying cells

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $355,080

## Abstract

Project Summary
This project studies the degradation of apoptotic cells after they are internalized into phagocytes. During
animal development and adulthood, cells undergoing apoptosis, a cell death process essential for animal
development and homeostasis, are rapidly internalized by other cells via phagocytosis (engulfment) and
degraded inside engulfing cells. The removal of apoptotic cells provides a safe means for eliminating
unwanted and dangerous cells from the body. Furthermore, it prevents tissue injury, inflammatory responses,
and auto-immune responses that could be induced by the content of dead cells. The study of apoptotic-cell
removal has also inspired the development of novel cancer treatment strategies. Given the strong evolutionary
conservation of developmental mechanisms, what we learn from C. elegans will be translated to humans. My
long-term objective is to understand the molecular mechanism that controls the recognition, engulfment, and
degradation of apoptotic cells, using the nematode Caenorhabditis elegans as a model organism.
This project focuses on two aspects important for the degradation of the engulfed apoptotic cells, which are
confined in a vacuolar structure called a “phagosome”. Phagosomes undergo a “maturation” process through
a series of membrane trafficking events that lead to the incorporation of multiple types of intracellular
organelles into phagosomes and the deposition of digestive enzymes into phagosomal lumen. As a result the
cargo inside a phagosome is digested, the digested substances and the phagosomal membrane are exported,
and a phagosome is resolved. Many questions remain unexplored regarding the degradation of a phagosome.
Our studies will establish a novel functional relationship between autophagy and phagocytosis (Aims 1 and 2).
In particular, we will demonstrate that autophagosomes, which are double-membrane intracellular organelles
whose primary role is to clear cellular aggregates and inactive macromolecule complexes and organelles, is a
new kind of organelles that are recruited to phagosomal surface and fuse with phagosomes (Aim 1). We will
further explore whether the fusion between autophagosomes and phagosomes is a conserved event in
mammals (Aim 2). In a separate project, we will investigate two propose mechanisms that regulate
“phagosome resolution”, the completion of degradation and the export of phagosomal contents (Aim 3). The
proposed work will have broad impact in revealing novel mechanisms of intracellular signaling and membrane
trafficking, which are essential for animal development.

## Key facts

- **NIH application ID:** 10145007
- **Project number:** 5R01GM067848-17
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Zheng Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,080
- **Award type:** 5
- **Project period:** 2003-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145007

## Citation

> US National Institutes of Health, RePORTER application 10145007, Degradation of dying cells (5R01GM067848-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145007. Licensed CC0.

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