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Antimicrobial Resistance and Gene Regulation in Enteroaggregative Escherichia coli

Aston University College of Health and Life Sciences
Partially Funded 🎓 Nursing & Health antimicrobial resistance genome analysis synthetic biology enteroaggregative escherichia coli gene regulation aggR biofilm virulence

Explore how a novel AggR variant controls virulence in antibiotic-resistant EAEC strains. Use genome analysis and synthetic biology to develop potential new therapies against EAEC infections.

AI-generated overview

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Why This Research Matters

This research addresses antimicrobial resistance in a globally significant pathogen causing diarrhoeal disease, especially in vulnerable populations. Understanding gene regulation in EAEC and developing genetic strategies to reduce virulence could lead to novel therapies and improved health outcomes.

Bacterial gene expression Recombinant Protein Production Bacterial chromosome structure Outer membrane biogenesis in Gram-neg

Project Description

Project Overview

Enteroaggregative Escherichia coli (EAEC) are significant bacterial pathogens causing diarrhoeal disease worldwide, particularly affecting children and immunocompromised patients. These strains adhere to gastric mucosa and establish biofilms, secreting toxins that cause tissue damage. Increasing antimicrobial resistance among EAEC strains limits treatment options. This project aims to elucidate how a variant of the AggR transcription factor regulates virulence genes and contributes to antimicrobial resistance, using genomic and molecular biology approaches.

What You Will Do

The student will analyse sequenced genomes of EAEC strains isolated from Egyptian and Brazilian children, characterizing antibiotic resistance genes, virulence factors, and plasmid content. Using synthetic biology techniques, the student will engineer mutant versions of AggR to modulate gene expression by blocking specific promoters, thus exploring novel therapeutic strategies to prevent infection.

Expected Outcomes

This research will clarify the gene regulatory mechanisms behind EAEC pathogenicity and antimicrobial resistance. The project aims to identify key genes regulated by the novel AggR variant and assess the potential of engineered mutants to reduce virulence, laying groundwork for new antimicrobial therapies targeting EAEC infections.

Why This Matters

Understanding EAEC gene regulation is critical to combating diarrhoeal diseases that impact global health, particularly in vulnerable populations. Addressing antimicrobial resistance in these pathogens aligns with urgent public health priorities and may inform development of innovative therapeutics to mitigate EAEC-related morbidity.

Entry Requirements

Candidates should have a First or Upper Second Class undergraduate degree in a relevant subject, or a First or Upper Second Class undergraduate degree plus a Merit or Distinction in a relevant Masters. Overseas qualifications must be equivalent.

How to Apply

Submit a complete application including higher education transcripts, research statement, personal statement, CV, two academic references, English language evidence, and passport copy if applicable. Contact Dr Douglas Browning at d.browning@aston.ac.uk for enquiries. Interviews are conducted online via Microsoft Teams.

Eligibility

UK/Home
EU
International

Supervisor Profile

DD
Dr Douglas Browning
Aston University, College of Health and Life Sciences
6405 Citations
36 h-index
Google Scholar

Dr Douglas Browning is a researcher at Aston University's College of Health and Life Sciences focusing on bacterial gene regulation and pathogenesis. He studies Enteroaggregative Escherichia coli, particularly mechanisms controlling virulence and antimicrobial resistance. His work applies molecular biology and synthetic biology to understand and combat infectious diseases.

Key Publications

2004 1390 citations
The regulation of bacterial transcription initiation
2016 651 citations
Local and global regulation of transcription initiation in bacteria
2010 390 citations
Modulation of Shigella virulence in response to available oxygen in vivo
2010 381 citations
Effects of nucleoid-associated proteins on bacterial chromosome structure and gene expression
2000 275 citations
Regulation of Acetyl Coenzyme A Synthetase inEscherichia coli

Research Contributions

Studied the regulation mechanisms of bacterial transcription initiation at both local and global levels.
This research advances understanding of bacterial gene regulation, which is crucial for microbiology and antibiotic development.
Analyzed effects of nucleoid-associated proteins on bacterial chromosome structure and gene expression.
Helped elucidate bacterial chromosome organization influencing gene expression and cellular function.
Investigated outer membrane biogenesis and structure, including components of the β-barrel assembly machinery.
Contributed knowledge for targeting bacterial outer membranes in infectious disease control.
Explored modulation of bacterial virulence in response to environmental factors like oxygen availability.
Provides insights into pathogen behavior during infection, informing therapeutic strategies.

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