Professor David Grainger

Supervisor Details

Contact Details

School of Biosciences, University of Birmingham

Scientific Background

Research Interests

Bacterial chromosome biology, pathogenicity and antibiotic resistance mechanisms.
High-throughput analysis of DNA binding events.
Single molecule analysis.

Work in David’s laboratory is focused on understanding the biology of bacterial chromosomes. Consequently, he is interested in a broad range of biological processes that directly require the interaction of DNA with other cellular machinery. His current research interests include understanding how i) gene regulation is managed on a chromosome-wide scale ii) pathogens control the production of toxins and iii) molecular pathways to multiple antibiotic resistance.

Scientific Inspiration

Lots of other scientists inspire me, for many different reasons.

Research Groups

Grainger Lab

Institute of Microbiology and Infection

Supervision Style

In three words or phrases: student-oriented, supportive, relaxed.

Provision of Training

You will mostly be trained in the laboratory by experienced post-docs and PhD students. I will provide training on project design, critical thinking, presentation and data analysis, and scientific writing.

Progression Monitoring and Management

I meet weekly with all PhD students so that we can discuss progress, design experiments, and trouble shoot problems. These meetings also provide an opportunity to set long term plans and consider where you are with respect to achieving these.

Communication

I try to speak briefly with all members of the group daily. Sometimes this will be just for a few minutes. On other occasions, these evolve into longer chats about your project and generate new ideas. Otherwise, I primarily communicate with lab members by email. The group as a whole also uses a WhatsApp group chat.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per week

In year 3 of PhD study

At least once per week

These meetings will be mainly face to face. I am usually contactable for an instant response on every working day.

Working Patterns

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Primary supervisor for:

Understanding the pandemic microbe Vibrio cholerae

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Understanding the pandemic microbe Vibrio cholerae

Secondary Supervisor(s): Prof Andy Lovering

University of Registration: University of Birmingham

BBSRC Research Themes:

Sustainable Agriculture and Food (Microbial Food Safety)

Project Outline

Understanding the rules of species evolution is a fundamental question in biology. The emergence, spread and demise of harmful organisms, which can cause pandemics, is particularly important. You will focus on the bacterial species Vibrio cholerae. Currently, we cannot explain how the strain causing the current cholera pandemic arose, let alone predict why, where or when the next one might arise. The “success” of V. cholerae depends on its ability to adapt to different surroundings. Normally, the bacterium resides in aquatic environments and persists by forming biofilms on the chitinous surfaces of plankton and shellfish. These biofilms are rapidly disassembled on ingestion by a human or aquatic host. Following host colonisation, disease is caused by the extrusion of toxins. Hence, to understand what is special about the “pandemic” strain, it is essential to understand how the bacterium is able to switch between lifestyles. Recent work has generated a wealth of V. cholerae genome sequences (>10,000) from decades of outbreaks associated with the current worldwide pandemic. You will use these data to try and understand key genetic changes that influence lifestyle choice and pandemic potential. You will apply bacterial genomics, molecular biology, and host organism colonisation models, to study lifestyle changes.

Haycocks, JRJ, Warren, GZL, Walker, LM, Chlebek, JL, Dalia, TN, Dalia, AB, Grainger, D (2019) The quorum sensing transcription factor AphA directly regulates natural competence in Vibrio cholerae. PLoS Genetics. 15:e1008362.

Walker, LM, Haycocks, JRJ, van Kessel, JC, Dalia, TN, Dalia, AB, Grainger, D (2023) A simple mechanism for integration of quorum sensing and cAMP signalling in V. cholerae. eLife 12:RP86699

Understanding multiple antibiotic resistance mechanisms in pathogenic bacteria

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Understanding multiple antibiotic resistance mechanisms in pathogenic bacteria

Secondary Supervisor(s): Prof Jessica Blair

University of Registration: University of Birmingham

BBSRC Research Themes:

Sustainable Agriculture and Food (Animal Health and Welfare, Microbial Food Safety)

Project Outline

We are offering two possible projects to study antibiotic resistance mechanisms.

Project 1: Understanding multiple antibiotic resistance in the ESKAPE pathogen Acinetobacter baumannii. Acinetobacter baumannii is a World Health Organisation “priority pathogen” of greatest risk to human health. The bacterium undergoes frequent phenotypic change, believed critical to its success. The mechanistic basis, and clinical implications, are not known. We have discovered a process never described for bacteria; specific A. baumannii gene clusters are “marked”, by chromosome folding, for frequent disruption by transposable DNA (1). Genes impacted are those involved in pathogenicity and antibiotic resistance, and we propose this is how A. baumannii generates phenotypic variation in its populations to cause disease and persist in hospitals. We have recently obtained £3.5M in research funding to study this problem alongside scientists at the Universities of Oxford and Exeter. As a MIBTP funded student, you will work with this research team, providing excellent opportunities for additional training and mentorship. You will learn to use microbiology tools, infection models, and collaborate with clinicians. The aim is to determine how targeted transposition allows A. baumannii, and other bacterial pathogens, to rapidly adapt to stresses including antibiotics and the human immune system.

Project 2: Understanding the multiple antibiotic resistance gene regulatory system of enteric pathogens. In human pathogens, including Escherichia coli and Salmonella species, a small group of AraC-XylS family transcription factors drive resistance to antibiotics by altering gene expression. The primary example is the multiple antibiotic resistance activator, MarA, protein of E. coli (2,3). Antibiotic resistant bacteria can carry genetic changes meaning MarA is produced all the time and at high levels (2). Upon expression, MarA alters gene expression globally, by binding DNA sites called marboxes, and this drives antibiotic resistance (2,3). Whilst some aspects of the response are understood, such as up-regulation of efflux pump expression, most MarA regulated genes are unknown or have no obvious connection to drug resistance (3).

We have developed an approach to accurately identify MarA regulated genes (3). Furthermore, by mutating marboxes at different chromosomal sites, we have discovered strong synergistic interactions, between regulated genes, that individually appear inconsequential (4). This project will build on these findings to answer two major questions: which genes are controlled by MarA and how do synergistic interactions between them drive antibiotic resistance? You can expect to learn a wide range of molecular biology techniques, both laboratory based and computational. The lab approaches will include whole genome and focused molecular microbiological tools.

References

1. Cooper, C et al. Nature Commun. 15:7137 (2024)

2. Blair, J. M. A. et al. Nature Reviews Microbiology 13, 42–51 (2015)

3. Sharma, P. et al. Nat. Commun. 8, 1444 (2017)

4. Trigg, A. et al. PLoS Genet. 21: e1011639 (2025)

Co-supervisor on a project with Dr Damon Huber.