About the project

Bacteria constantly adapt to their environment and respond to stresses and toxic compounds that they encounter. Without this adaptation, bacteria would die. A common mechanism that protects bacteria against toxic molecules such as antibiotics and biocides are efflux pumps, molecular machines that pump such molecules out of the cell. It is known that efflux of antibiotics can lead to antibiotic resistance, and more recently efflux pumps have also been used to protect bacteria against organic solvents and other chemicals in industrial processes.

We have recently found that there is a fundamental link between the way in which bacteria generate energy (needed for growth and cellular functions) and efflux pumps (required for removing harmful chemicals) [Whittle et al. 2023]. Energy is needed to drive efflux pumps, but we have discovered that the energy level within the cell is responsible for regulating fundamental behaviours, and that efflux pumps impact on these behaviours.

We think that this is very important in understanding how bacteria are able to survive in different environments, including during infections and in industrial processes. In this project we will explore this link and aim to understand how we might use this knowledge to kill pathogenic bacteria via better use of antibiotics and improve industrial processes.

The main research questions are:

• How is the energy state of the cell linked to efflux pumps?
• How is this link regulated? What are the sensors and regulators involved in this process?
• How does the energy – efflux link allow bacteria to become resistant to antibiotics
• How can we use this link to improve bacterial processes that generate useful compounds?

We will use a combination of approaches, grounded in single-cell analysis of bacteria using flow cytometry and microscopy that we have previously developed [Whittle et al. 2019]. This will allow us to measure how individual bacteria respond to stresses, regulate their energy state, and control efflux pumps. We will also use a variety of molecular biology methods to generically modify bacteria in order to better understand mechanisms of energy metabolism, efflux, and their regulation.

This topic is incredibly important as antibiotic resistance is an urgent and growing problem that threatens global health. The World Health Organisation estimate that 1.3 million deaths were caused by AMR in 2019, and AMR contributed to 5 million deaths; and these numbers are growing year on year. There are already bacteria causing disease that cannot be treated using antibiotics. In addition, antibiotics are required for preventing infection following operations and chemotherapy, meaning that many aspects of modern medicine would fail if antibiotics became less effective.

This interdisciplinary project will be supervised by Dr Tim Overton (School of Chemical Engineering), who is an expert on single-cell analysis of bacteria and bacterial physiology, and Professor Jessica Blair (Institute of Microbiology and Infection), an expert on bacterial efflux pumps and antimicrobial resistance.

We welcome informal enquiries and discussions about the project - please contact Tim Overton (t.w.overton@bham.ac.uk).

References

• Whittle EE, Legood SW, Alav I, Dulyayangkul P, Overton TW, Blair JMA. (2019) Flow Cytometric Analysis of Efflux by Dye Accumulation. Front Microbiol. doi: 10.3389/fmicb.2019.02319.
• Whittle EE, Orababa O, Osgerby A, Element SJ, Blair JMA, Overton TW. (2023) Efflux pumps mediate changes to fundamental bacterial physiology via membrane potential. bioRxiv doi: 10.1101/2023.04.03.535035

Entry Requirements

Applicants will be expected to have a good Honours degree (First Class or Upper Second Class Honours degree) awarded by a recognised University in life science (e.g. Biology, Biochemistry, Biotechnology, Microbiology) or physical science (e.g. Chemistry, Chemical Engineering) disciplines.

What does the scholarship provide?

1. Financial Support: Recipients of these scholarships will receive substantial financial support, including a stipend at UKRI rates, which is set at £18,622 per year. This support covers tuition fees, living expenses, and research-related costs, including bench fees. This support is designed to alleviate the financial burden often associated with pursuing a doctoral degree.
2. Mentorship and Guidance: Scholarship recipients will benefit from mentorship opportunities and guidance from accomplished faculty members who are dedicated to helping them succeed in their academic and research endeavours.
3. Research Opportunities: We are committed to providing an exceptional research environment. Students will have access to state-of-the-art facilities, cutting-edge resources, and a vibrant scholarly community.
4. Community Building: A key component of the scholarship programme is the creation of a supportive community of Black British researchers pursuing PhDs. This network will foster collaboration and peer support among scholars.
5. Research Training Support Grant: In addition to financial support, scholarship recipients will receive a research training support grant. This grant is intended to support conference attendance, fieldwork, and other essential activities that enhance their research and academic growth.
6. Commitment to Inclusivity: We are dedicated to building an inclusive academic environment that values diversity and ensures equitable access to education.

Contact the lead supervisor

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