What is the basis of antibiotic resistance in Gram-negative bacteria?

Gram-negative bacteria cause a wide range of infections, including pneumonias, urinary tract infections, bacteraemia, and sepsis. The recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to such infections. At the same time, Gram-negative bacteria have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. Reductionist scientific approaches have identified many virulence factors which have been well studied in models of infection. However, the mechanisms of resistance to antibiotics have not been well studied. To identify the genes required for antibiotic resistance a whole genome screening approach will be used. Using high density transposon mutagenesis coupled with next generation sequencing all genes essential for viability under standard laboratory conditions and in the presence of several clinically relevant antibiotics will be assessed. Organisms being studied include Escherichia coli, Salmonella enterica, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Corynebacterium diptheriae etc.

In this project you will select an organism for further characterisation. The objectives of the project can be shaped by the interests of the student but will loosely follow the follow ambitions

1. Make high density transposon libraries and screen against antibiotics

2. Determine the regulatory network for the gene of interest using RNAseq to interrogate genes expression in wild-type and mutant cells

3. Investigate how the protein encoded by the gene of interest is regulated or how it regulates other genes. This will be done using DNA footprinting assays and in vitro transcription assays. These tools are used routinely in the lab and all of the required materials are already available

4. Explore how the gene of interest shapes multidrug resistance by comparing the MICs of mutants with the wildtype strains. Studying whether loss of the gene confers a fitness cost for the bacterium and has downstream effects on metabolism

At the University of Birmingham, Institute of Microbiology and Infection, you will be part of a vibrant and lively postgraduate community and one of the world-leading institutes for microbiological and infectious disease research.

Person Specification
If you are an enthusiastic scientist with an interest in host-pathogen interactions, looking for a PhD position, we would be happy to hear from you. A background in immunology, microbiology or molecular genetics would be helpful. An enthusiastic approach to science, together with the ability to take ownership of your own project within a young, dynamic research team, is essential. You should have a commitment to academic research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.

How to apply
Informal enquiries should be directed to Prof. Ian Henderson
Applications should be directed to Ian Henderson (email [Email Address Removed]). To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable;
• All applicants should indicate in their applications how they intend to fund their studies.

Funding notes:
We have a thriving community of international PhD students and encourage applications at any time from students able to find their own funding or who wish to apply for their own funding (e.g. Commonwealth Scholarship, Islamic Development Bank).

The Institute of Microbiology and Infection offers a number of UK Research Council (http://www2.warwick.ac.uk/fac/cross_fac/mibtp/; http://www.birmingham.ac.uk/schools/mds-graduate-school/scholarships/mrc-impact/index.aspx) PhD studentships each year and studentships funded by Wellcome (http://www.birmingham.ac.uk/schools/mds-graduate-school/wellcome-aamr/index.aspx; http://www.birmingham.ac.uk/schools/mds-graduate-school/scholarships/wellcome.aspx). Fully-funded research council studentships are normally only available to UK nationals (or EU nationals resident in the UK) but part-funded studentships may be available to EU applicants resident outside of the UK. The deadline for applications for research council and Wellcome studentships is in January each year.

Each year we also have a number of fully funded Darwin Trust Scholarships (http://www.birmingham.ac.uk/postgraduate/funding/darwin-studentships.aspx). These are provided by the Darwin Trust of Edinburgh and are for non-UK students wishing to undertake a PhD in the general area of Molecular Microbiology. The deadline for this scheme is also in January each year.

Please note the only funding available for this PhD is via the Scholarships mentioned.