Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli.

Details of the Project

Enteroaggregative Escherichia coli (EAEC) is a major cause of diarrhoeal disease in industrialized and non-industrialized countries and has been shown to be the cause of travellers’ diarrhoea and persistent diarrhoea in children and HIV patients. EAEC strains cause disease by binding to the human gastric mucosa and establishing a thick mucoid biofilm, damaging tissue by secreting various toxins [1]. In spite of their widespread occurrence and impact on human health, little is known about how EAEC strains control the expression of genes required to establish infection and cause disease. Furthermore, EAEC strains are increasingly resistant to many clinical antibiotics, decreasing treatment options [1-4]. Thus, there is a need to understand EAEC pathology and devise new methods to combat this important group of bacterial pathogens.

In many EAEC strains, the expression of important virulence determinants (e.g., the attachment adherence fimbriae (AAF) required for colonization, the anti-aggregative protein dispersin (Aap) and its dedicated secretion system) is controlled by the AggR transcription factor, the master regulator of virulence [1-3]. Recently, we have been working with EAEC strains isolated from Egyptian and Brazilian children with diarrhoea [3,4]. In these strains, we have found a new version of AggR that controls gene expression differently. Thus, the main aim of this project will be to determine how this version of AggR controls virulence and determine the genes that it regulates. We have already had the genomes of many of these strains fully sequenced, and so part of this project will be to analyse their genomes to determine each strains characteristics (e.g., antibiotic resistance gene profile, virulence determinants and plasmid replicons etc.). The project will also use synthetic biology to engineer and deliver mutant versions of AggR into EAEC cells, blocking specific promoters and virulence gene expression, as a potential therapeutic approach to combating EAEC infection.

Overseas Applicants

Overseas applicants may apply for this studentship but will need to pay the difference between the ‘Home’ and the ‘Overseas’ tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7. As part of the application, you will be required to confirm that you will provide this additional funding. Please indicate this on the application form in the funding section. This project has associated consumables costs which should be discussed with the supervisor in the first instance and before applying. The supervisor can be contacted at d.browning@aston.ac.uk. When applying, please upload copies of your discussions with the supervisor as confirmation.

Location

This position will be based on the Aston Campus in Birmingham, UK. The successful candidate will need to be located within a reasonable distance of the campus, and will be expected to visit in person regularly.

Person Specification

Candidates should have been awarded, or expect to achieve, EITHER:

a] a First or Upper Second Class award in their undergraduate degree, in a relevant subject.

OR

b] a First or Upper Second Class award in their undergraduate degree, and a Merit or Distinction in a Masters degree, both in a relevant subject.

Qualifications from overseas institutions will be considered, but performance must be equivalent to that described above, and the University reserves the right to ascertain this equivalence according to its own criteria.

Contact information

For formal enquiries about this project contact Dr Douglas Browning at d.browning@aston.ac.uk

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected.Your application must include:

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor degrees.
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count.
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience.
4. A Curriculum Vitae (Resume) which details your education and work history.
5. Two academic refereeswho can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary.
6. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage.
7. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.

Apply for this position here

Please select “Research - Health Sciences” from the application form options.

If you require further information about the application process please contact the Postgraduate Admissions team at pgr_admissions@aston.ac.uk

Funding Notes

This project covers the Home tuition fees. Candidates who do not have Home status will be responsible for the difference in tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7. This project has associated consumables costs which should be discussed with the supervisor in the first instance and before applying. The supervisor can be contacted at d.browning@aston.ac.uk. When applying, please upload copies of your discussions with the supervisor as confirmation.