Muscle aging and gene expression balance in Caenorhabditis elegans

Lead Research Organisation: University of Leeds
Department Name: Inst of Integrative & Comparative Biolog

Abstract

Genome editing based on CRISPR-Cas9 is now rapid and straightforward in Caenorhabditis elegans and has opened up entirely new avenues of research in this key model system. Precise manipulations of promoter regions in situ will allow subtle modification in vivo of expression levels of proteins with roles in control of muscle calcium ion homeostasis. Discordance in levels of subunits of the complex calcium ion channel regulatory system is predicted to lead to muscle ageing, the major factor in mobility decline in older people. A better understanding of muscle ageing in animals may lead to delaying of muscle ageing in people.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1827305 Studentship BB/M011151/1 30/09/2015 29/02/2020 Brittany Graham
 
Description Novel consequences of disease variants in the ryanodine receptor were found in the nematode C. elegans. Eight genome-edited strains were generated carrying known disease variants in the ryanodine receptor. These disease variants are normally associated with increased sensitivity to anaesthetics. Increased sensitivity to an anaesthetic was found in all strains, as well as altered locomotion in the absence of the anaesthetic. Further to the novel finding of altered locomotion in the absence of anaesthetic triggers, age-related consequences were found in the absence of such triggers. The normal effects of ageing were exacerbated in strains carrying the disease variants. The effects of these disease variants in nerve and muscle cells was assessed but was not conclusive, although an effect of these variants in nerve cells is suspected.
Exploitation Route The suspected neural effects of these variants could be explored further in C. elegans. The novel locomotion defects may have consequences in mammalian models of ryanodine receptor variants and even for humans, this could be assessed. Furthermore, the exacerbated ageing needs to be addressed in mammalian models as this could have consequences for the world's ageing population.
Sectors Healthcare