Bioactive natural products from the microbiome – an innovative approach to healthy ageing (CASE project)

Primary Supervisor: Dr Marina Ezcurra (Biology of Ageing at Biosciences, University of Kent)

Secondary Supervisor: Dr Kieron Edwards (Chief Scientific Officer at Sibelius Natural Products)

Project Summary

The gut microbiome is a promising but unexplored avenue to improve health. In humans, certain microbial species are associated with improvements in multiple aspects of age-related health. Experiments using model organisms show that the microbiome directly impacts on ageing, and that microbial effects on ageing are evolutionary conserved. Studies in both humans and animals show that the microbiome secretes compounds that improve ageing. Together these results show that the microbiome holds a huge potential to promote health during ageing.

Novel approaches to understand host-microbiome interactions: The challenges with studying the microbiome arise from its enormous complexity and the cost associated with studying the microbiome using murine models. If our understanding of host-microbiome interactions is to move beyond association and generate a mechanistic understanding, allowing the development of innovative microbiome-based interventions, cost-effective models and unbiased high-throughput studies are needed. The nematode C. elegans offers such a system. It is inexpensive and genetically tractable, ideally suited for mechanistic studies of host-microbiome interactions shaping host physiology and health.

The Ezcurra lab has established a novel system to study host-microbiome interactions using C. elegans, and identified secreted microbial products improving proteostasis and mitochondrial function in the host. Sibelius Natural Products has developed ChronoscreenTM, a platform using C. elegans and evidence-based approaches to evaluate effects natural products on healthy ageing. Building on these earlier findings the student will develop the use of ChronoscreenTM and C. elegans to enable microbiome-based strategies to promote healthy ageing and evaluation of their translational potential.

Aims: We will screen newly isolated bacterial species for compounds improving ageing in C. elegans. The compounds will be characterised in detail and the underlying host-microbiome mechanisms improving host ageing will identified. We will develop a pre-clinical pipeline to generate microbiome-based solutions to healthy ageing and provide scientific evidence to support investment in clinical trials.