# CELL DEATH IN A HIGH CONNECTIVITYU INVERTEBRATE MODEL

> **NIH NIH R01** · ST. JOHN'S UNIVERSITY · 1993 · $173,177

## Abstract

We propose research to identify and characterize proteins controlling
cell death and the rolling genes controlling these proteins.  The most
experimentally useful paradigm for cell death is insect metamorphosis,
in which large masses of homogeneous tissues die synchronously and at
scheduled times.  Our previous studies have employed the intersegmental
muscles and labial gland of Manduca sexta, a 10 g insect which provides
substantial amounts of each tissue.  During cell death in these tissues,
synthesis of most proteins drops drastically while simultaneously
synthesis of a highly reproducible small set of proteins begins,
increases dramatically, or continues unabated, suggesting that these
latter proteins are intimately involved in the destruction of the cell.
Our earlier observation that protein synthesis is required for cell
death has been widely corroborated.  We are currently isolating
libraries of the genes which are up-regulated during cell death, with
the goal of identifying those genes responsible for determining the
lifespan of the cell.  The proposed research will extend these efforts,
and compare the genes of the hornworm to those in Drosophila, in order
to utilize and extend the high connectivity of Drosophila I genetics and
biology.  We will correlate morphological changes with appearance of
specific messages and proteins, and determine which proteins are common
to Manduca muscle and labial gland.  We will also sequence the
up-regulated proteins in order to generate antibodies and impute
functions if possible.  The antibodies will be used to locate the
proteins in the dying cells.  Second, we will isolate and characterize
common cDNAs activated during different stages of involution and
likewise use these to characterize the activity of the genes.  Finally,
we will search for homologous genes in Drosophila. Identification of
these genes in Drosophila will permit us to locate them on the
Drosophila chromosome and by selection of appropriate mutants or
P-element transformation control the activity of the genes in order to
determine the extent to which they control cell death.  Identification
of Manduca in Drosophila will select for conserved genes.  The knowledge
gained is expected to be applicable to mammalian systems.  Knowledge of
how cells define their own vulnerability should be valuable for
therapeutic considerations, as similar genes are expected to be found in
embryonic differentiation, malignant growth and invasion, and aging.  It
is also likely that a better understanding of normal cell turnover will
come from the study of programmed cell death.

## Key facts

- **NIH application ID:** 3122054
- **Project number:** 5R01AG010101-03
- **Recipient organization:** ST. JOHN'S UNIVERSITY
- **SAM.gov UEI:** QMCKV4B31PG2
- **Principal Investigator:** Richard A. Lockshin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $173,177
- **Award type:** 5
- **Project period:** 1991-06-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122054

## Citation

> US National Institutes of Health, RePORTER application 3122054, CELL DEATH IN A HIGH CONNECTIVITYU INVERTEBRATE MODEL (5R01AG010101-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122054. Licensed CC0.

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