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(BBSRC DTP) Bacterial excretion - implications for biotechnology and antimicrobial resistance


Project Description

This PhD project will exploit new ways of working by providing training in a variety of approaches namely this will include lab based skills in molecular and microbiology, data processing and statistical analysis, and analytical flow methods such FACS. This will provide the PhD student with the ability to use and apply quantitative data-driven approaches to more fully understand biological questions. In addition to the training the research project goals/outputs in themselves will exploit new ways of working, as they will provide innovative tools and technological approaches for the generation of highly productive processes for high-vale fine chemicals and insights into bacterial cell transport.

Two major challenges facing society in the 21st century are: i) How can we live and consume in a more sustainable manner?
ii) How can we avoid the re-emergence of untreatable bacterial infections?

Related to these challenges we recently discovered that under conditions of osmotic and translation stress bacterial cells undergo an excretion phenomenon, whereby abundant cellular components are expelled into the extracellular environment [1]. The scope of this project is to explore the implications of bacterial excretion upon both biotechnology and antimicrobial resistance. Sustainable production of fine and platform chemicals, using engineered microorganisms, has potential to reduce our dependency on fossil fuel based feedstocks. Whereas, antimicrobial resistance is the critical healthcare challenge of the 21st and we as a society are facing a post-antibiotic era.

Project Aims:
a) To engineer variant bacterial strains to permit enhanced productivity from heterologous biosynthetic pathways. This will involve genetically engineering E. coli strains to contain the desired mutants and knock-outs. These engineered E. coli stains will be used with established plasmid-based heterologous biosynthetic pathways for the production of high-vale fine chemicals, via the Synthetic Biology Centre (SYNBIOCHEM), for example those used in the flavour and fragrance industry.

b) To understand the implications of cellular stress and excretion upon bacterial antimicrobial resistance. Specifically, how cellular stress and excretion are involved in bacterial cells avoiding death following treatment with antibiotics [2].

The PhD student based in Manchester Institute of Biotechnology will be co-supervised by Dr. Neil Dixon, Prof Nigel Scutton, and Dr Jen Cavet. The student will be trained in broad aspects of biotechnology, synthetic biology, microbiology, gene expression regulation, molecular biology and analytical flow methods. This project would suit individuals interested in future careers in biotechnology, drug discovery, and anti-microbial target validation.

Contact for further information:

http://www.manchester.ac.uk/research/neil.dixon/
dixonlab.org
https://www.research.manchester.ac.uk/portal/jennifer.s.cavet.html
https://www.research.manchester.ac.uk/portal/Nigel.Scrutton.html

Entry requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

[1] Morra, R., Del Carratore, F., Muhamadali, H., Horga, L., Halliwell, S., Goodacre, R., Breitling, R. & Dixon, N. Translation Stress Positively Regulates MscL-Dependent Excretion of Cytoplasmic Proteins mBio (2018), doi.org/10.1128/mBio.02118-17 [2] Wray R, Iscla I, Gao Y, Li H,, Wang J, Blount P. PLoS Biol. 2016 Jun 9;14 :e1002473 Dihydrostreptomycin Directly Binds to, Modulates, and Passes through the MscL Channel Pore

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