# Genetic Control of Programmed Cell Death (Apoptosis) and Compensatory Proliferation in Drosophila

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $125,000

## Abstract

Project Summary (from parent grant R35 GM118330)
Genetic Control of Apoptosis and Apoptosis-induced Proliferation in
Drosophila
Principal Investigator: Andreas Bergmann, Ph.D.
 Programmed cell death (PCD) or apoptosis is a physiological process that is critical for normal
development and tissue homeostasis. Defects in the regulation of PCD contribute to the pathogenesis of
multiple diseases including those associated with reduced rates of cell death (cancer, autoimmunity) or
with excessive cell death (neurodegeneration, stroke, myocardial infarction).
 Apoptosis-induced proliferation (AiP) describes the recently made discovery that apoptotic
cells have the ability to induce proliferation of neighboring surviving cells, thus compensating for their
loss. For instance, despite massive apoptotic tissue loss of up to 60% triggered by ionizing radiation,
Drosophila wing imaginal discs induce regenerative cell proliferation which generates adult wings of
normal proportion and size. Unexpectedly, evidence obtained in several organisms including Drosophila,
Xenopus, Hydra, Mouse and human cancer suggests that regenerative AiP of amputated or otherwise
damaged tissues including tumors depends on apoptotic caspases (highly specific cell death proteases)
in a non-apoptotic function.
 The overall objective of this scientific program is to gain a comprehensive understanding of
the biological principles that underlie the regulation of apoptosis and AiP in the context of a multi-cellular
organism, to identify and characterize the genes involved in these processes, and to develop methods to
manipulate them.
 We are using the genetic model organism Drosophila melanogaster for these studies. During
Drosophila development many cells die by apoptosis. This cell death shares this developmental plasticity
with vertebrates. Genetic screening for gene discovery and molecular genetic analysis in Drosophila
promise considerable potential for advancing our understanding of the basic control mechanisms
involved in the regulation of apoptosis and AiP in vertebrates including humans.
 This program is also very relevant for understanding of human cancer. Our studies elucidate
mechanisms by which potential tumor cells increase their resistance to apoptosis, a hallmark of cancer,
which may generate immortalized (undead) cells. Moreover, recent evidence has suggested that
apoptotic tumor cells promote caspase-dependent AiP. For example, although radio- and chemotherapy
attempt to cure cancer by killing tumor cells, relapse of treated tumors is frequently observed which may
be due to an AiP-promoting activity of dying tumor cells.
 In summary, this program promises to improve our understanding of apoptosis and regenerative
proliferation under normal conditions and tumor phenotypes under pathological conditions.

## Key facts

- **NIH application ID:** 10135259
- **Project number:** 3R35GM118330-05S1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** ANDREAS BERGMANN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $125,000
- **Award type:** 3
- **Project period:** 2016-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135259

## Citation

> US National Institutes of Health, RePORTER application 10135259, Genetic Control of Programmed Cell Death (Apoptosis) and Compensatory Proliferation in Drosophila (3R35GM118330-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135259. Licensed CC0.

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