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  Identifying the antibiotics and antibiotic resistance genes that shape a microbiome (HUTCHINGS_UJIC23ARIES)


   Graduate Programme

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  Prof M Hutchings  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Scientific background

Microbiomes offer great benefits to their hosts, including nutrient acquisition, growth promotion, immunity, and defence against disease but they are complex and difficult to study. As a result, insects have emerged as simple, experimentally tractable models with which to study microbiomes.

 Our model is the leafcutter ant Acromyrmex echinatior, which has a simple cuticular microbiome dominated by antibiotic-producing bacteria that protect the ants against disease. The question in this project is how do the ants recruit antibiotic-producing (useful) bacteria while keeping out all other (cheater) bacteria?

 Hypothesis

We know the ants pass a single strain of antibiotic-producing Pseudonocardia bacteria from generation to generation. Preliminary data suggest these are bacteriocin-type antibiotics. We have shown in vitro that this vertically transmitted strain could result in selective acquisition of antibiotic-producing Streptomyces bacteria, resulting in a defensive microbiome producing multiple types of antibiotics that is robust to the evolution of resistance by pathogens. Antibiotic-producing bacteria are necessarily themselves antibiotic resistant, and are pre-adapted to the Pseudonocardia-toxin-infused ant cuticle, allowing them to consume nutrients provided by the ants to their cuticular microbiome.

 Research methodology

The student will test the prediction that only antibiotic-producing bacteria that are resistant to Pseudonocardia antibiotics can colonise the ant cuticle, and this is why the ants are able to selectively recruit a microbiome dominated by Pseudonocardia and Streptomyces bacteria. This will involve:

1.   Identifying the antibiotics made by the Pseudonocardia bacteria.

2.   Testing them for activity against a range of different bacteria.

3.   Determining their mode(s) of action.

4.   Identifying the antibiotic resistance genes (ARGs) that make Streptomyces bacteria resistant.

 Training

The student will be based at JIC where Hutchings and Wilkinson share laboratory space equipped for molecular microbiology and natural products chemistry. They will receive full training in microbiology, bioinformatics, antibiotic bioassays, purification of natural products and mass spectrometry.

 Training will be provided by the supervisors and their groups, including core funded RAs. Support will also be provided by senior support scientists running bioinformatics, chemistry, metabolomics, and proteomics science platforms at JIC.

Person specification 

The student should have a first degree and/or Masters in biology or chemistry.

Biological Sciences (4)

Funding Notes

This project has been shortlisted for funding by the ARIES NERC DTP. Successful candidates will be awarded a NERC studentship, which covers fees, stipend (£17,668 for 2022/23) and funding to support the doctoral research. Excellent applicants from quantitative disciplines may be considered for an additional three months’ studentship funding.
Unfortunately, no additional funding is available to assist with relocation or visa costs.
ARIES encourages applications from all, regardless of gender, ethnicity, disability, age, or sexual orientation. Academic qualifications are considered alongside relevant non-academic experience.
For further information, please visit www.aries-dtp.ac.uk

References

1 Worsley SF, Innocent TM, Holmes NA, Wilkinson B, Murrell JC, Boomsma JJ, Yu DW and Hutchings MI (2021). Competition-based screening secures the evolutionary stability of a defensive microbiome. BMC Biology 19:205.
2 Heine D, Holmes NA, Worsley SF, Alve dos Santos AC, Innocent TM, Scherlach K, Patrick E, Yu DW, Murrell JC, Boomsma JJ, Hertweck C, Hutchings MI* and Wilkinson B* (2018). Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen. Nature Comms. 9:2208.
3 Holmes N, Innocent T, Heine D, Worsley S, Findlay K, Murrell J.C., Wilkinson B*, Boomsma JJ* and Hutchings MI* (2016). Genome analysis of two Pseudonocardia phylotypes associated with Acromyrmex leafcutter ants reveals their biosynthetic potential. Front Microbiol. 7:2073
4 Batey SFD, Greco C, Hutchings MI and Wilkinson B (2020). Chemical warfare between fungus growing ants and their pathogens. Curr Op Chem Biol 59:172-181.
5 Barke, J., Seipke, R.F., Gruschow, S., Heavens, D., Drou, N., Bibb, M.J., Goss, R.J.M., Yu, D.W. and Hutchings, M. I. (2010). A mixed community of actinomycetes produce multiple antibiotics for the fungus farming ant Acromyrmex octospinosus. BMC Biology 8:109
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