Investigating the Localisation and Action of Vitamin B12 in C. elegans

Cobalamin, also known as vitamin B12, is used as a coenzyme for key enzymes involved in the S-adenosyl methionine (SAM) cycle and branched-chain amino acid (BCAA) metabolism, which lead to many downstream targets. Thus, B12 is required for many physiological functions including DNA synthesis, cell division, erythrocyte production, and myelin sheath maintenance. Biologically active B12 is produced by a select group of bacteria, mainly by fermentation in the gastrointestinal tract of animals, and archaea. Humans must acquire B12 from animal products, and B12 deficiency is associated with pernicious anaemia and neural deterioration. However, deficiency is only acquired after several years, therefore studying B12 action and transport in an animal model where B12-deficiency can be induced in a few weeks is both cost- and time-efficient. This project investigates the role and transport of B12 in the nematode C. elegans, with the outlook that it could be used as a whole animal model to fully understand its action. B12-deficiency was induced in C. elegans by growing them on media lacking this vitamin, and found that it caused delayed life cycle, reduced lifespan, and a reduction in progeny. After noticing that B12 deficiency had a negative impact on lifespan, and knowing that B12 is important for neuronal function in humans, the effects of B12-deficency on C. elegans neuronal branching with age, which is related to neurodegeneration, were examined. We found that B12-deficient worms had earlier-onset and increased neurite branching indicating the interesting possibility that this aspect of B12 function could be modelled in worms. In conclusion, we found that B12-deficiency had a detrimental effect on C. elegans health in general, and that this nematode is a good model for studying the action of vitamin B12 in vivo