The human body is home to a vast ecosystem of microorganisms including bacteria, archaea, fungi, viruses, and bacteriophages that make up the human microbiota. These microbes and their collective genetic material, known as the microbiome, influence a wide range of physiological functions including nutrient production and absorption, the development and regulation of our immune system, protection against potential pathogens, and even our mood and mental health. While distinct microbial communities exist throughout the body, the gut microbiome has gained particular attention in recent years given its link to several diseases including inflammatory bowel disease, metabolic disorders and cancer.
Viruses that infect bacteria and archaea are particularly unstudied in the human microbiome, due to their extreme diversity. Recently it has been shown that large viruses with genomes in excess of 500,000 base pairs are present in both human and animal gut microbiomes (Devoto et. al. 2020), suggesting that many more groups of these 'megaphages' remain to be discovered. In contrast to the recovery of draft bacterial and archaeal genomes, which is now relatively routine, finding novel viruses directly from metagenomic datasets is comparatively challenging. While collections of bacterial and archaeal sequences assembled from metagenomic datasets can be assessed as being near-complete with well-established tools, there are no similar tools for viruses. Thus, we may already have thousands of viral genomes assembled in our databases, and simply not know it.
This project will use a newly developed tool which is able to find megaphages genomes derived from metagenomic sequencing of human gut samples. It is anticipated that application of this tool to hundreds to thousands of human microbiomes will yield many such megaphages. Further project work will focus on characterising these viruses in terms of their gene complement, determining which bacteria or archaea they infect, and their relationship to human disease state.
(Devoto, A.E., Santini, J.M., Olm, M.R. et al. Megaphages infect Prevotella and variants are widespread in gut microbiomes. Nat Microbiol 4, 693–700 (2019).)
Research activities include:
- metagenomic analysis techniques including genome-centric metagenomics
- viral gene and genome annotation – which genes to the viruses encode and what is the taxonomic classification of the found viruses?
- data science and visualisation – relating disease state with viral load, using correlation and co-evolution to determine the host range of discovered viruses – likely using either Python or R.
- microbial community profiling
- usage of various bioinformatic programs e.g. the Lorikeet tool to determine strain genotypes and abundance.
Outcomes of the research will be the results of an exploration into large viruses in the human microbiome. Analysing thousands of microbiome samples will give an indication of the prevalence of these viruses in better-studied human populations, and viral genome characterisation efforts will help elucidate the human health and ecological implications of their presence in gut samples. Understanding the viral mechanisms involved in disease initiation and progression could help guide the development of new diagnostics and/or therapeutics that will benefit patients affected by a range of diseases.
Skills and experience
Contact the supervisor for more information or visit the Centre for Microbiome Research.