Molecular footprints of mechanosensation

Bacterial membranes can sense mechanical pressure, which is important as it could indicate that they are about to burst due to high internal, hydrostatic pressure. This is however avoided thanks to channel proteins such as MscL (Mechano-sensitive channel of Large conductance) which can act as pressure relieve valves. Similar proteins are also important for temperature sensations in humans, yet our understanding of the mechanism of mechanosensation is lacking. How are mechanical forces, via lipid tethering, pulling on the protein structure to open the channel? Can we lock this mechanism, using mutations or specific lipids, at various stages? Can we follow it in “real time” using fast (ms-μs) labelling techniques?

We have access to over 50 MscL mutants and will study their behavior using innovative, fast labelling techniques such as hydrogen/deuterium exchange and hydroxyl radical labeling with a readout based on mass spectrometry (MS). Together with data from electron paramagnetic resonance (EPR), we can create detailed simulations of these interesting and important proteins and their function. You will work with experts in their respective fields (Membrane protein structural biology, MS, EPR and simulations) and have a unique opportunity to gain expertise in cutting-edge integrative structural biology technology.