**PLEASE NOTE – the deadline for requesting a funding pack from Darwin Trust has now passed and completed funding applications must be submitted to Darwin Trust by 19th January. We can still accept applications for this project from self-funding students.
Maintaining intracellular homeostases is a hallmark of life, and key physiological variables, such as cytoplasmic pH, osmotic pressure, and proton motive force (PMF), are typically interdependent. However, they are mostly looked in isolation, as if they were independent. Furthermore, the regulation of the PMF and other ion motive forces (IMFs) is hardly ever considered, even though PMF is one of the main energy sources in living organisms. In fact, one could argue that living cells area proton batteries, and that we bread and eat to charge them. Providing that energy to living processes is as important as understanding the information processing (i.e. the DNA), yet it is hardly studied. The most likely reason is the interdisciplinary nature of the question.
Recently, we have developed a mathematical model focused on these links that includes the PMF/IMF maintenance, and by looking at the relevant dependencies, we were able to predict that Escherichia coli uses proton-ion antiporters to generate membrane potential and so maintain the PMF at the constant levels we observed experimentally.
Consequently, the strength of the PMF determines the range of extracellular pH over which the cell can preserve its near neutral cytoplasmic pH. We concurrently measure the PMF and cytoplasmic pH in single cells and demonstrated our model prediction. This result suggests a new perspective on bacterial electrophysiology, where cells regulate the membrane potential by changing the activities of antiporters to maintain both the PMF and cytoplasmic pH. To conclusively prove this novel perspective in this project we will alter the available ion efflux pumps in E. coli and observe the consequences on the PMF and membrane voltage. Furthermore, by doing so we will try to understand why E. coli maintains a specific internal pH and PMF value. Overall the project will offer exciting new insight into the energy maintenance of living organisms.
https://pilizotalab.bio.ed.ac.uk/
https://swainlab.bio.ed.ac.uk/
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