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Unraveling the Secrets of Ribosome (Im)mortality

Unraveling the Secrets of Ribosome (Im)mortality

Brigitte Pertschy (ORCID: 0000-0003-3558-0191)
  • Grant DOI 10.55776/TAI1570824
  • Funding program 1000 Ideas
  • Status ongoing
  • Start January 1, 2025
  • End August 31, 2026
  • Funding amount € 186,782

Disciplines

Biology (100%)

Keywords

    Ribosome Biogenesis, Ribosome Degradation, Caenorhabditis elegans

Abstract

Ribosomes are essential nanofactories for protein synthesis, with each cell containing hundreds of thousands to millions of ribosomes. During cell division, the entire pool must be duplicated, making ribosome synthesis a crucial step for cell proliferation. However, it is unclear whether ribosome synthesis is necessary in non-dividing cells, such as most tissue cells. Unlike other biomolecules that undergo rapid turnover, ribosomes are believed to be extremely stable. Degradation mechanisms for ribosomes have been described but typically only occur under specific conditions, such as when ribosomes are defective or need to be reduced to save energy. This project aims to determine whether ribosomes are immortal, rendering new ribosome synthesis in non-dividing cells unnecessary, or if ribosomes, like other biomolecules, undergo turnover, with old ribosomes being replaced by new ones. Traditional models for studying ribosome synthesis and degradation have high proliferation rates, making it challenging to assess ribosome dynamics independent of cell division. To address our research questions, we will use the worm Caenorhabitis elegans (C. elegans) as a model. Adult C. elegans have a constant number of approximately 1000 cells throughout their three-weeks lifespan, providing a unique system to measure ribosome synthesis and decay rates in non- proliferating cells. By inhibiting ribosome biogenesis and assessing the impact on the functionality of aging ribosomes and the worms lifespan, we aim to elucidate the importance of ribosome biogenesis in non-dividing cells. Clarifying these questions will be a significant breakthrough in the fields of ribosome biogenesis and degradation. If we discover that ribosomes degrade over time, this model will enable the study of natural ribosome degradation mechanisms. Conversely, if we find that ribosome biogenesis is crucial for non-dividing cells, it will pave the way for research on ribosome biogenesis in tissue cells. Importantly, ribosome biogenesis is a promising target for antiproliferative drugs in cancer therapy. Our findings on the relevance of this pathway in non-dividing cells will provide valuable insights into the potential side effects of these drugs on non-proliferating cells.

Research institution(s)
  • Universität Graz - 100%

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