Finding needles in haystacks – sequencing single bacteria from complex microbiomes

MACAULAY_E22DTP2

Microbiomes are integral to many of the fundamental processes affecting society – from healthcare to agriculture – but the complexity and diversity harboured within these microbiomes and the roles of individual cells/species in adaptation to new environments/stresses is still largely unexplored. Traditionally, microbiome complexity is assessed using a metagenomic approach, where DNA extracted from bulk microbial pools is sequenced and the relative abundance of individual species is inferred from the data.

In this project, we will bring single-cell genomics techniques to the study of complex, real-world microbiomes. This will enable access to rare, unculturable cells, from which we can generate detailed, rich genomic information. Such cells may only constitute a tiny subfraction of the overall population but may be critical for the overall impact or function of the microbial community. We hypothesise that the detailed whole-genome sequencing of rare microbiome components will reveal genetic diversity that cannot be observed by classical metagenomics approaches. Recent work from our lab has demonstrated the feasibility of single-cell, whole bacterial genome sequencing – with near complete genomes and single nucleotide variation data being attainable from single cells (Bawn et al. 2020).

Using a range of techniques, including FACS, single-cell genomics, next generation short- and long- read sequencing and bioinformatic analysis, the student will develop tools to isolate and analyse the genomes of individual cells from complex microbiomes. The student will subsequently apply these advances to the study of rare components of human microbiomes, revealing the extent of genetic diversity in these populations, beyond what could be observed with classical metagenomics.

Based in the Macaulay lab at the Earlham Insititute, the student will also work in close collaboration with the Hildebrand (QIB) and Quince (EI) groups, receiving extensive training in experimental and computational biology, developing a broad and transferrable expertise in cellular and microbial genomics.

References

Bacterial single-cell genomics enables phylogenetic analysis and reveals population structures from in vitro evolutionary studies. Matt Bawn, Johana Hernandez, Eleftheria Trampari, Gaetan Thilliez, Mark A. Webber, Robert A. Kingsley, Neil Hall, Iain C. Macaulay bioRxiv 2020.08.25.266213; doi: https://doi.org/10.1101/2020.08.25.266213