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(BBSRC NWD) Moving like lemmings: collective migration towards antibiotics within bacterial biofilms

Funding
Funded
Study mode
Full-time
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Start date
Subject area
Biological and Biomedical Sciences
How to apply
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Overview

Pseudomonas aeruginosa is a globally significant “priority” bacterial pathogen (World Health Organisation) that causes biofilm-associated, antibiotic-resistant infections. Whilst P. aeruginosa is widely studied in liquid-culture, most cells in natural and clinical settings live within surface-attached biofilms. In liquid-culture, bacteria swim using flagella, whilst on surfaces, P. aeruginosa crawls using pili (molecular grappling-hooks). Whilst bacteria swim away from harmful chemicals, we find that surface-attached P. aeruginosa counter-intuitively crawls towards – rather than away from – clinically significant antibiotics, a novel behaviour we call ‘antibiotic taxis’.

About this opportunity

We speculate that antibiotic taxis enables P. aeruginosa to counterattack antibiotic-secreting competitors, but we know little about the genetic, behavioural or ecological basis of this paradoxical behaviour.

To date, antibiotic taxis has been observed in isolated bacteria at low cell densities within microfluidic devices that expose cells to precisely defined antibiotic gradients. Studying cells at low cell densities allows us to track individual bacteria and analyse their behaviour. However, most bacteria live in dense biofilms, and we do not know how cells might respond to antibiotic gradients in a biofilm context. We are therefore developing a novel microfluidic system to grow bacterial colonies at the interface between an agar-pad and a glass coverslip, and then expose these colonies to steady, defined chemical gradients by infusing fluid along two separate channels either side of the colonies. By infusing antibiotics through one of the two channels, we can expose colonies to antibiotic gradients that form as the antibiotics diffuse through the agar. Crucially, colonies of P. aeruginosa grow as 2D monolayers when sandwiched between agar and glass. This allows us to use our state-of-the-art imaging and cell-tracking pipeline to quantify individual cell behaviour within these biofilms. The method combines machine-learning based cell-tracking software with fluorescently-labelled proteins, whose sub-cellular localisation reflects the localisation of the pili that cells use to move across surfaces. This project will combine these two novel methodologies to provide fundamentally new insight into how bacteria navigate chemical gradients within biofilms.

This is a highly interdisciplinary project that will combine microfluidics, automated-microscopy, machine-learning, massively parallel cell-tracking and molecular microbiology. This work will build on our recent high-profile publications that have reported initial observations of antibiotic taxis in isolated bacterial cells, and complements existing funded work aiming to answer critical questions that have arisen from these initial observations.

Further reading

[1] Oliveira NM, Wheeler JHR, Deroy C, Booth SC, Walsh EJ, Durham WM, Foster KR. Suicidal chemotaxis in bacteria. Nature Communications, 13, 7608 (2022).
[2] Wheeler JHR, Foster KR, Durham WM. Bacteria use spatial sensing to direct chemotaxis on surfaces. Nature Microbiology, 9, 2308–2322 (2024).
[3] Deroy C, Wheeler JHR, Rumianek AN, Cook PR, Durham WM, Foster KR, Walsh EJ. Reconfigurable microfluidic circuits for isolating and retrieving cells of interest. ACS Appl. Mater. Interfaces, 14 (22), 25209-25219 (2022).
[4] Tank RKG, Lund VA, Kumar S, Turner RD, Lafage L, Pasquina-Lemonche L, Bullough PA, Cadby A, Foster SJ, Hobbs JK. Correlative Super-Resolution Optical and Atomic Force Microscopy Reveals Relationships between Bacterial Cell Wall Architecture and Synthesis in Bacillus subtilis. ACS Nano, 15(10), 16011–16018. (2021)
[5] Wilson SA, Tank RKG, Hobbs JK, Foster S, Garner EC. An exhaustive multiple knockout approach to understanding cell wall hydrolase function in Bacillus subtilis. mBio, 14(5), e01760-23. doi:10.1128/mbio.01760-23. (2023).
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Who is this for?

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

International applicants

We are only able to offer a limited number of full studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality international candidates due to the competitive nature of this scheme.

International applicants must ensure they meet the academic eligibility criteria (including English language) before applying. Visit our English Language requirements page to find out more.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Liverpool, and is at the heart of all of our activities. The full equality, diversity and inclusion statement can be found on our website.

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How to apply

  1. 1. Contact supervisors

    You’ll be joining a friendly and collaborative team led by Dr Jamie Wheeler (a molecular microbiologist and biophysicist with expertise in microscopy, cell-tracking and molecular techniques) Dr Raveen Tank (a biophysicist with expertise in microfluidics, microscopy and women’s health) and Prof Jian Lu, a professor of biological physics. We provide an inclusive research culture that encourages curiosity and openness, as well as varied and fulfilling personal lives. We will support researchers with caring responsibilities, and offer a flexible working environment throughout the PhD. Weekly meetings alongside regular training/ networking events will foster a diverse skillset aimed at building quantitative assays that leverage large datasets to answer fundamental questions in microbiology.

    For informal enquiries, please contact  or .

  2. 2. Prepare your application documents

    Browse our BBSRC NWD in Bioscience projects and discover one you’re passionate about that matches your interests, ambitions and goals.

    Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

    How to Apply

    All applications should be submitted through the University of Manchester application portal.

    Apply directly via this link, and select BBSRC DTP PhD as the programme of study. You may apply for up to two projects from the programme via this scheme. To do so, submit a single online application listing both project titles and the names of both main supervisors in the relevant sections.

    Please ensure that your application includes all required supporting documents:

    • Curriculum Vitae (CV)
    • Supporting Statement
    • Academic Certificates and Transcripts

    Incomplete or late applications will not be considered.

    Applications should not be made through the University of Liverpool’s application portal.

    You must submit your application form along with the required supporting documents by the deadline date. You can select up to two projects on one single application, noting the title of each project from the advert and the supervisor name. This can include two projects from one institution or a project from each institution.

    Once you have completed your application, you’ll receive a confirmation email.

    Deadline: Sunday 7th December, midnight (UK time)

    Late or incomplete applications will not be considered.

    If you need help with this stage of the process, or have any queries regarding your eligibility (such as if you achieved unexpectedly low degree results due to extenuating circumstances), please contact the Liverpool BBSRC team for advice at 

  3. 3. Apply

    Finally, register and apply online. You'll receive an email acknowledgment once you've submitted your application. We'll be in touch with further details about what happens next.

    Once you have applied through the University of Manchester portal, and if you are successfully offered a studentship following a formal interview, you will be instructed to apply formally through the University of Liverpool. You must only do this once you have been instructed to do so.

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Funding your PhD

These studentships are available to UK and international applicants, and provide funding for tuition fees and stipend at the UKRI rate, subject to eligibility, for four years. This does not include any costs associated with relocation. This scheme is open to both UK and international applicants.

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Contact us

Have a question about this research opportunity or studying a PhD with us? Please get in touch with us, using the contact details below, and we’ll be happy to assist you.

Liverpool BBSRC team
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