PhD Studentship - Improving the Solvent Tolerance of E. Coli by Understanding the Rules of Accumulation

Gram negative bacteria such as E. coli use two main mechanisms to survive in the presence of a range of toxic molecules such as antibiotics, biocides, and solvents. First, their envelope prevents entry of these molecules. Second, efflux pumps actively pump toxic molecules outside of the cell. Together, these mechanisms limit intracellular accumulation and so allow bacteria to resist toxicity. We have recently discovered that bacteria preferentially use these two mechanisms at different times; efflux pumps are more important in rapid growth, whereas the envelope barrier predominates in slower growth [1].

This PhD project seeks to leverage our new understanding of the ways in which bacteria control accumulation of toxic molecules to improve solvent tolerance in E. coli. There is an urgent need to develop new sustainable processes to make a range of chemicals, allowing us to move away from crude oil as a precursor of products such as plastics, fuels, and pharmaceuticals.

One way to achieve this is using bacteria to transform waste materials into useful chemicals and products. However, yields of many organic chemical products are low, in part due to their toxicity to bacteria. If we understand how accumulation can be limited, we can engineer bacteria to become more solvent-tolerant and thereby generate higher yields of useful products [2].

The project supervisory team comprises Tim Overton (microbial physiology, bioprocessing), Sara Jabbari (mathematical modelling) and Jess Blair (efflux pumps, antimicrobial resistance), each of whom will bring their expertise to guide the project.

The exact scope of the project will be guided by the student. We will start by understanding how solvents enter and leave bacterial cells, and how solvents affect bacterial physiology. Later stages of the project could combine microbiology with quantitative modelling, engineer bacterial strains with improved solvent tolerance, or develop intensified bioreactor processes, depending upon your interests. Final stages will compare our starting conditions with our new improved process or strains.

You will be working in a large supportive multidisciplinary team that spans four UK institutions (Birmingham, Imperial College, Nottingham, and Quadram) as part of the major BBSRC-funded sLoLa BARRIΣR project investigating mechanisms of antimicrobial accumulation in bacteria. There will be opportunities to collaborate more broadly and develop expertise across this group.

Applicants should have or expect to obtain at least an Upper Second-Class Honours Degree in a relevant subject such as life or physical sciences.

Please note that this advert may close earlier than the stated closing date if sufficient strong applications are received. Interested candidates should contact Tim Overton via t.w.overton@bham.ac.uk for informal enquiries, and before applying should provide a CV, referee’s and cover letter summarising their research interests and previous experience.

Funding notes

This project is funded by the University of Birmingham and is open to UK students only.

References

Whittle EE, McNeil HE, Trampari E, Webber M, Overton TW, Blair JMA. Efflux Impacts Intracellular Accumulation Only in Actively Growing Bacterial Cells. mBio. 2021 Oct 26;12(5):e0260821. doi: 10.1128/mBio.02608-21.
2. Yang D, Prabowo CPS, Eun H, Park SY, Cho IJ, Jiao S, Lee SY. Escherichia coli as a platform microbial host for systems metabolic engineering. Essays Biochem. 2021 Jul 26;65(2):225-246. doi: 10.1042/EBC20200172.

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