Investigating mechanisms of protein aggregate transmission in C. elegans
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The transfer of toxic, aggregated forms of proteins between cells drives the progression of neurodegenerative diseases. However, the mechanisms driving this propagation are not yet fully understood. This project aims to decipher these mechanisms, using in vitro and in vivo methods that we have developed in the tractable invertebrate model organism Caenorhabditis elegans (C. elegans). One of these methods is a novel model for the transmission of human disease-associated proteins between cells and tissues in C. elegans. This model will be screened for genes that affect the spreading of protein aggregates, and these genes then studied to identify mechanisms that modulate this spreading. The project will also utilise a new method of C. elegans cellular co-culture, which will allow the study of protein transmission between different cell types within a defined in vitro system. Finally, the mechanisms identified will then be characterised in mammalian cell culture models. We aim to define therapeutically-relevant mechanisms responsible for the transmission of protein aggregates in neurodegenerative disease.