# The coordination of cell death and corpse clearance

> **NIH NIH R35** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2020 · $450,219

## Abstract

Project Summary
Cell death is a fundamental process in animal development and homeostasis, and 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. The research in this proposal focuses on four key questions. 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, and current work
investigates the role of lysosomes and cell signaling in this process. 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 can improve their phagocytic
capacity is not known, and our research program will reveal the requirements for engulfment by
epithelial cells. A third project addresses how phagocytic cells can promote the death of their
neighbors, through a newly described type of cell death called phagoptosis. In the fourth project,
we investigate the consequences of persisting cell corpses in the ovary and the brain, and how
defective phagocytosis can affect disease progression. We will examine the global changes to
organisms with defective cell death or phagocytosis and how defective phagocytosis interacts
with genetic models of human disease. Given the high degree of conservation of cell death
mechanisms between Drosophila and mammals identified thus far, 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. These studies may reveal new therapeutic
targets for diseases with excessive or insufficient cell death such as neurodegenerative
disorders and cancer.

## Key facts

- **NIH application ID:** 9894653
- **Project number:** 5R35GM127338-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Kimberly A McCall
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,219
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894653

## Citation

> US National Institutes of Health, RePORTER application 9894653, The coordination of cell death and corpse clearance (5R35GM127338-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894653. Licensed CC0.

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