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Establishing universal principles for invasion of the microbiome in the context of disease


   School of Biosciences

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  Prof James McDonald, Dr MJ Cox  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Background: Pathogen invasion and establishment within the existing microbial community of a host is a central feature of disease development. Consequently, various factors including colonisation resistance, microbe-microbe interactions, pathogen and host microbiota abundance, and host immunity will dictate the outcome of pathogen invasion. The design and testing of synthetic microbial communities in combination with DNA sequencing and computational analyses now provide tractable systems to test and establish the ecological principles that underpin pathogen invasion and dominance in disease.

The overall aim of this project is to explore the factors the dictate the success of pathogen invasion and dominance within microbial communities associated with two contrasting disease systems; Acute Oak Decline in trees and Chronic Obstructive Pulmonary Disease in humans. Both diseases involve microbial pathogens, a pre-existing microbial community and a eukaryotic host, though the organisms involved, the nature of the host and the function and complexity of the microbiome are different. By contrasting these two disease systems, the candidate will experimentally identify common features in the nature and response of the microbiome. Ultimately this will help to identify mechanisms to exploit to prevent or resolve disease and to manipulate host-associated microbiomes.

The candidate will utilise a range of methods (microbial culture, synthetic community design and assembly, in vitro competition assays, quantitative PCR, 16S rRNA gene community profiling, metagenomics and computational analyses) to address the following research objectives:

1 - Develop protocols for screening community structure of clinical and plant tissue samples using Oxford Nanopore technology. Determining whether a microbiome is dominated by one organism (uneven) or multiple organisms are present in similar abundance (even) is a key indicator of pathogenic processes. We need to be able to rapidly and cheaply identify even and uneven communities, just as we establish other basic parameters, such as measuring pH or temperature. The candidate will develop rapid, multiplexed sample screening methods using the ONT MinION with flongle flow cells.

2 - To utilise the Nanopore metagenome sequencing protocol developed in objective 1 in combination with quantitative PCR and16S rRNA gene community profiling to assess the relationship between pathogen abundance, taxonomic and functional diversity, and bacterial abundance in clinical and plant tissue samples.

3 - Finally, using data from objective 2 the candidate will design and test synthetic microbial communities to explore the factors influencing pathogen invasion success (e.g. community diversity, metabolic repertoire, competition, abundance of microbial community, pathogen load)

Funding Notes:

Please visit the Midlands Integrative Biosciences Training Partnership (MIBTP) website for further information about funding availability and eligibility requirements: https://www.birmingham.ac.uk/research/activity/mibtp/index.aspx


References

McDonald James E., Marchesi Julian R. and Koskella Britt (2020) Application of ecological and evolutionary theory to microbiome community dynamics across systems. Proc. R. Soc. B. 287: http://doi.org/10.1098/rspb.2020.2886
Denman, S., Doonan, J., Ransom-Jones, E., Broberg, M., Plummer, S., Kirk, S. A., Scarlett, K., Griffiths, A., Kaczmarek, M., Foster, J., Peace, A., Golyshin, P., Hassard, F., Brown, N., Kenny, J. G. & McDonald, J. (2018) Microbiome and infectivity studies reveal complex polyspecies tree disease in Acute Oak Decline. The ISME Journal. 12, p. 386-399
Chotirmall SH, Bogaert D, Chalmers JD, Cox MJ, Hansbro PM, Huang YJ, Molyneaux PL, O'Dwyer DN, Pragman AA, Rogers GB, Segal LN, Dickson RP. Therapeutic Targeting of the Respiratory Microbiome. Am J Respir Crit Care Med. 2022 Sep 1;206(5):535-544. doi: 10.1164/rccm.202112-2704PP. PMID: 35549655.
Antwis RE, Harrison XA, Cox MJ (2020) Microbiomes of soils, plants and animals: an integrated approach. Cambridge University Press ISBN:9781108654418 https://doi.org/10.1017/9781108654418

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