# In Vivo Genetic Analysis of Compartmentalized Cell Elimination

> **NIH NIH R35** · UNIVERSITY OF TEXAS ARLINGTON · 2022 · $375,345

## Abstract

Project Summary/Abstract
Programmed cell death (PCD) and has vital roles in organismal health and is essential to normal development.
Apoptosis is genetically programmed and mutations in regulatory genes contribute greatly to cancer therapy
resistance. Timely clearance of cellular debris following cell death is also critical as defects lead to inflammation
and are linked to autoimmune disease. Most cells in the body are highly differentiated and have intricate
morphologies. This presents challenges in the execution of cell death and clearance, as the subcellular
architecture and microenvironment of different compartments of the same cell may differ vastly. Complex cells
can die as a whole or in part. In the case of region-specific degeneration, cellular extensions are exclusively
dismantled leaving the rest of the cell intact. For neurons, such pruning is important in establishing appropriate
connectivity and thus for proper brain function. The central question addressed here is how morphologically
complex cells are eliminated. The C. elegans tail-spike cell is a valuable model to study complex cell
degeneration, dying through an elaborate, likely universal, compartment-specific program of cell death during
embryonic development. We have termed this remarkable program Compartmentalized Cell Elimination (CCE),
which also occurs in a set of sex-specific neurons, suggesting this may be a universal program of death. The
tail-spike cell also shows differential genetic regulation at the levels of both compartmental killing and clearance.
As such, a study of this single cell can provide insights on many facets of cell elimination. This proposal
leverages the fact that the tail-spike cell can be studied in its native context in the living animal as well as the
facile genetics of C. elegans to tackle three broadly related overarching questions: How does mitochondrial
trafficking influence cell process elimination? What novel genes govern CCE and hence cell death and removal
broadly? What novel genes regulate CCE in other complex cells, such as neurons? We will perform advanced
cell biological and genetic studies to address these questions. The proposed experiments, by illuminating
fundamental principles of basic cell biology, will advance the field of cell death in several ways. They will
identify novel regulators of PCD and clearance; they hold the potential to help devise targeted therapies against
cell-death-related disease, including cancer, neurodegeneration, immune and developmental disorders.

## Key facts

- **NIH application ID:** 10456274
- **Project number:** 5R35GM142489-02
- **Recipient organization:** UNIVERSITY OF TEXAS ARLINGTON
- **Principal Investigator:** Piya Ghose
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $375,345
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456274

## Citation

> US National Institutes of Health, RePORTER application 10456274, In Vivo Genetic Analysis of Compartmentalized Cell Elimination (5R35GM142489-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10456274. Licensed CC0.

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