# The coordination of cell death and corpse clearance in Drosophila

> **NIH NIH R35** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $794,500

## Abstract

Project Summary
Cell death is a fundamental process in animal development and homeostasis. Misregulation of
cell death is associated with a large number of human diseases. Our research program aims to
understand the diverse mechanisms of cell death, how dead cells are efficiently removed, and
the physiological effects on organisms when these processes go awry. We study these
questions in Drosophila, a model organism with exceptional genetic, genomic and cell biological
tools. Our research program focuses on several major projects. The first project investigates
non-apoptotic cell death which contributes significantly to development and disease, but is
poorly understood. In the Drosophila ovary, germline-derived nurse cells undergo non-apoptotic
programmed cell death as part of normal development. We have found that nurse cell death is
controlled largely non-autonomously by the surrounding somatic follicle cells by phagocytic and
lysosomal proteins. Ongoing work will uncover the subcellular mechanisms controlling nurse cell
destruction. A second major project investigates how dead cells are removed, particularly in
tissues without access to circulating phagocytes such as macrophages. In many mammalian
tissues, dead cells can be cleared by epithelial cells. In a Drosophila model for engulfment by
epithelial cells, starvation induces degeneration of egg chambers, where the germline is
engulfed by the surrounding epithelial follicle cells. This engulfment process happens
synchronously and rapidly at the onset of cell death; however, the genetic requirements for
engulfment by epithelial cells are not well understood. In particular, how such non-professional
phagocytes increase their phagocytic capacity is not known. Our research program is revealing
how epithelial cells transform to a phagocytic state and how they act to promote cell death. A
third project addresses the consequences of defective phagocytosis in the brain which we have
found leads to neurodegeneration and immune activation. Future work will investigate the links
between phagocytosis, immune signaling and neurodegeneration. We will determine the cell-
type-specific responses to defective phagocytosis and susceptibility to neurodegeneration. A
fourth project investigates cross-tissue interactions in response to cell death in the maintenance
of homeostasis. Given the high degree of conservation of cell death mechanisms between
Drosophila and mammals, we expect that pathways that we uncover in the fly will provide
insight into the diversity of cell death mechanisms and consequences of defective cell removal
in humans.

## Key facts

- **NIH application ID:** 10764561
- **Project number:** 2R35GM127338-06
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Kimberly A McCall
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $794,500
- **Award type:** 2
- **Project period:** 2018-04-01 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764561

## Citation

> US National Institutes of Health, RePORTER application 10764561, The coordination of cell death and corpse clearance in Drosophila (2R35GM127338-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10764561. Licensed CC0.

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