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The Biophysics of Force Sensing Membrane Proteins by High-Speed Atomic Force Microscopy


   Faculty of Engineering and Physical Sciences

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  Dr G Heath, Dr C Pliotas  Applications accepted all year round  Competition Funded PhD Project (Students Worldwide)

About the Project

High-speed atomic force microscopy (HS AFM) captures 3D videos of molecules on the nanoscale at rates of up to 20 frames per second in liquid. By filming proteins important in biology we can capture complex behaviour and structural dynamics at high resolution. Within cell membranes, mechanosensitive channels are found throughout all forms of life acting as sensors for a number of systems including touch, hearing, gravity, osmotic pressure and cardiovascular regulation. These force sensitive channels open upon specific mechanical activation allowing certain molecules to enter or exist cells. This PhD project will use state-of-the-art HS-AFM to directly watch conformational dynamics of single membrane proteins the at the nanoscale in response to force. 

In cells these proteins are vital for many physiological functions consequently problems such as genetic mutations have been implicated in a number of severe human diseases. On the other hand, bacteria use these channels to regulate their internal turgor cytoplasmic pressure in response to rapid osmotic changes in their environment. Despite their importance, the molecular mechanism behind how these proteins respond to membrane tension is unknown. Developing an understanding for these mechanisms will help resolve the molecular basis of disease and give insight into potential drug targets to fight antimicrobial resistant bacteria.  


Funding Notes

This project is eligible for several funding opportunities, therefore, we recommend that you visit our website for further information.

References

1) Heath, G.R., Kots, E., Robertson, J.L. et al. Localization atomic force microscopy. Nature 594, 385–390 (2021). https://doi.org/10.1038/s41586-021-03551-x
2) Heath, G.R., Scheuring, S. High-speed AFM height spectroscopy reveals µs-dynamics of unlabeled biomolecules. Nat Commun 9, 4983 (2018). https://doi.org/10.1038/s41467-018-07512-3
3) Kapsalis, C., Wang, B., El Mkami, H. et al. Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets. Nat Commun 10, 4619 (2019). https://doi.org/10.1038/s41467-019-12591-x

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