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Finding needles in haystacks: sequencing single bacteria from complex microbiomes (MACAULAY_E22DTP2)


   Graduate Programme

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  Dr Iain Macaulay  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

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 Institute, 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

The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to UK and international candidates for entry October 2021 and offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

This project has been shortlisted for funding by the NRPDTP programme. Shortlisted applicants will be interviewed on Tuesday 25th January, Wednesday 26th January and Thursday 27th January 2022.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.


Funding Notes

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) PhD studentship. The studentship includes payment of tuition fees (directly to the University), a stipend for each year of the studentship (2021/2 stipend rate: £15,609), and a Research Training Support Grant for each year of the studentship of £5,000 p.a.

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
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