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Identifying neuronal or muscle cell-specific suppressors that rescue motility defects in the ALS model of the nematode worm Caenorhabditis elegans

Periodic Reporting for period 1 - RescueMoDe (Identifying neuronal or muscle cell-specific suppressors that rescue motility defects in the ALS model of the nematode worm Caenorhabditis elegans)

Berichtszeitraum: 2021-08-02 bis 2023-08-01

I pursued a project to understand the mechanism behind a modifier of proteotoxicity using the nematode worm Caenorhabditis elegans. This modifier induces a protective effect in several worm models of ageing and neurodegeneration by extending lifespan and health span, indicating that it has a broadly neuroprotective effect. Understanding how it protects neurons can potentially lead to the development of new therapeutic strategies against ageing and neurodegenerative diseases.
Using novel genetic tools, I identified that this modifier of proteotoxicity improved the health of some types of neurons during ageing, while other types of neurons are less affected. I also optimised a genetic tool that enables rapid depletion of a protein of interest in C. elegans worms. Therefore we are now able to deplete this modifier in any tissue of interest and at any timepoint. Using this optimised tool, we plan to investigate the mechanism of this modifier of toxicity further in several C. elegans models of neurodegeneration.
My data implicates that this modifier of neurodegeneration is working on specific neuronal tissues. Further research is required to understand the exact neuroprotective effect of mechanism, but understanding the tissue localisation of these mechanisms in the future will help researchers develop targeted therapeutic strategies for ageing and neurodegenerative diseases.
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