Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAEC) is a major cause of diarrhoeal disease in industrialised and non-industrialised countries and is 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.

References: *Research from the host's laboratory

1. Harrington, S.M., Dudley, E.G. and Nataro, J.P. (2006.) Pathogenesis of enteroaggregative Escherichia coli infection. FEMS Microbiol Lett. 254(1):12-8. Review.
2. Yasir, M., Icke, C., Abdelwahab, R., Haycocks, J.R., Godfrey, R.E., Sazinas, P., Pallen, M.J., Henderson, I.R., Busby S.J.W. and Browning, D.F. (2019) Organization and architecture of AggR-dependent promoters from Enteroaggregative Escherichia coli. Molecular Microbiology. 111:534-551.
3. Abdelwahab, R., Yasir, M., Godfrey, R.E., Christie, G.S., Element, S.J., Saville, F., Hassan, E.A., Ahmed, E.H., Abu-Faddan, N.H., Daef, E.A., Busby, S.J.W. and Browning, D.F. (2021) Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli from Egyptian children with diarrhoea: similarities and differences. Virulence 12:57-74
4. França, F.L.S., Wells, T.J, Browning, D.F., Nogueira, R.T., Sarges, F.S., Pereira, A. C., Cunningham, A.F., Lucheze, K., Rosa, A.C.P., Henderson, I.R. and das Graças de Luna, M. (2013) Genotypic and phenotypic characterisation of enteroaggregative Escherichia coli from children in Rio de Janeiro, Brazil. PLOS ONE 10.1371/journal.pone.0069971.

Supervisors

Dr Douglas Browning

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries and developing lifelong skills. 

At Aston University, our Engineering and Physical Sciences PhD programmes will provide all the support and facilities you will need to develop into a leading researcher in your chosen field.  You will be welcomed into a supportive community with a shared enthusiasm for original research, where diversity and multidisciplinary is championed.

Person Specification

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

• A Bachelors degree in a relevant subject with an award of First Class or 2.1. 

OR 

• A Bachelors degree in a relevant subject with an award of First Class or 2.1, and a Masters degree in a relevant subject with an award of Merit or higher.

Qualifications from other countries which are considered by Aston University to be equivalent to that described above will be eligible to apply.

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's 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. Two academic referees who 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. 
    
5. 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. 
    
6. 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.  

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.

The variety of PhD project topics at Aston means that the destinations of our graduates vary substantially. Some choose to continue into academia, at either Aston or other leading institutions, while others go onto use their newly acquired skills in a range of research, healthcare, industry or charitable fields. When selecting your chosen PhD path at Aston, your supervisor will be able to provide you with relevant career opportunities that could be available to you in your specialist area.