# The molecular mechanism of LCD, a prevalent and conserved non-apoptotic cell death program

> **NIH NIH F32** · ROCKEFELLER UNIVERSITY · 2021 · $68,562

## Abstract

Project Summary/ Abstract
The long-term goal of the proposed research is to uncover molecular mechanism driving non-apoptotic cell
death in vertebrate development and disease. Programed cell death functions to sculpt organs, remodel
tissues, regulate cell number, and remove defective cells. While apoptosis is the most studied type of cell
death, it does not account for all cellular destruction during development. Studies in C. elegans have
uncovered a novel developmental cell death program, referred to as linker cell-type death (LCD), which is
morphologically and molecularly distinct from apoptosis. Cell death with LCD features is commonly observed
during vertebrate development and in patients and mouse models of neurodegenerative polyglutamine
diseases. This proposal seeks to identify molecular events driving LCD in C. elegans, and to test their
functional conservation in vertebrate settings. To rigorously investigate these mechanisms, this F32 proposal
combines training in genetics, microscopy and computational analysis in vertebrate and invertebrate model
systems to investigate the following specific aims: 1) identify molecular targets of the Ubiquitin Proteasome
System (UPS) that precipitate cell destruction during LCD in C. elegans by performing functional studies and
a yeast 2-hybrid screen; 2) uncover the molecular basis of LCD in vertebrates by developing a cell culture
assay, testing roles of homologs of C. elegans LCD genes, and conducting a whole-genome CRISPR/Cas9
screen in cultured mammalian cells. The studies proposed here will lead to the development of new markers
to distinguish among different types of cell death in vertebrate development and disease, while uncovering
the molecular underpinnings of LCD. Because LCD is a prevalent type of cell demise, this proposal may not
only shed light on basic aspects of development, neurodegeneration, and cancer, but could also eventually
uncover in-roads of clinical significance.

## Key facts

- **NIH application ID:** 10086321
- **Project number:** 5F32GM136011-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Olga Yarychkivska
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086321

## Citation

> US National Institutes of Health, RePORTER application 10086321, The molecular mechanism of LCD, a prevalent and conserved non-apoptotic cell death program (5F32GM136011-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10086321. Licensed CC0.

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