RescueMoDe · Identifying neuronal or muscle cell-specific suppressors that rescue motility defects in the ALS model of the nematode worm Caenorhabditis elegans
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-08-02 → 2023-11-27
- EU contribution
- €175,572
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Identifying neuronal or muscle cell-specific suppressors that rescue motility defects in the ALS model of the nematode worm Caenorhabditis elegans
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.
Data: CORDIS, © European Union
Project objective
Amyotrophic lateral sclerosis (ALS) is a fatal disease that progressively causes loss of neuronal and muscle function, for which there is no known cure. Although the genetic causes of ALS vary, the cytoplasmic accumulation of the TDP-43 protein in neurons is highly consistent among patients. Thus, TDP-43 is believed to be a point of convergence in the pathway responsible for ALS progression. However, while many genetic and cellular mechanisms have been linked to ALS, there is still a lack of understanding of the neuro-muscular interactions in ALS. In this project, we will identify neuronal or muscle cell-specific suppressors of motor impairment using an ALS model in the nematode worm Caenorhabditis elegans. In this model, transgenic C. elegans overexpress TDP-43 in the neurons, resulting in severe motility defects. We will use optogenetic tools to excite neurons and muscle cells separately in the C. elegans ALS model, contributing to our understanding of how TDP-43 accumulation affects tissue function. In addition, live in vivo microscopy of C. elegans will help us to elucidate the impact of TDP-43 on neuro-muscular interactions over time. Furthermore, novel automated tracking of the nematode worms enables high-throughput analysis of C. elegans mobility. Thus, we can efficiently analyse mobility when TDP-43 is overexpressed, and use this tracking for high-throughput screening of mutants that rescue the ALS phenotype. Once we have identified the mutants that Rescue Motility Defects (RescueMoDe), we will characterize their impact on neuronal and muscular function. Therefore, it will be possible to analyse the tissue-specific role of these candidates, and how they fit into the progression of TDP-43 toxicity in this system. Overall, we aim to further the understanding of ALS progression, which will allow a highly informed continuation of studies in mammalian cell culture or in murine model systems, which may lead to therapeutic research opportunities.
Original text from CORDIS.
Participants
- ACADEMISCH ZIEKENHUIS GRONINGEN · GroningenCoordinatorNetherlands
Links
Data: CORDIS, © European Union