PhD Studentship: Improving the solvent tolerance of E. coli by understanding the rules of accumulation

There is an industrial need to move away from crude oil as a precursor of a wide range 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.

Gram negative bacteria use two main mechanisms to survive in the presence of a range of molecules such as antibiotics, biocides, and solvents. First, their envelope prevents entry of such 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. 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, with the possibility to pursue scale-up of productive processes in bioreactors and / or mathematical modelling of solvent ingress and efflux from bacteria.

You will also be working in a large multidisciplinary team that spans four UK institutions as part of a BBSRC-funded sLoLa project investigating mechanisms of antimicrobial accumulation.

Please direct informal enquiries to Tim Overton – t.w.overton@bham.ac.uk

Funding notes:

This project is funded by the University of Birmingham and is open to UK students only.
We typically require a 2(i) degree in a relevant subject (life or physical sciences).

References:
1. 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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