Research project The physicochemical code for cellular function and extreme adaptation.

Will human proteins maintain human behaviour also in ‘foreign’ organisms like E. coli where they have not evolved? How does the functionally optimised charged distributions of the intra-cellular compartment compare with the universally used ‘physiological buffer’ controls, i.e. to what extent is the in-vivo environment non-ideal, and how do we correct for such deviations when translation in-vitro data to physiological conditions? The reason why these key issues have remained unresolved is that the experimental methods for studying proteins in vitro are challenging to adapt to the complex environment in live cells. To target this problem, we have developed new strategies for atomic-resolution analysis of protein structure, dynamics and interaction by in-cell NMR: in essence, we can monitor at unprecedented detail the structural behaviour of any small protein inside live mammalian and bacterial cells. Our aim is now to establish the very basics of how proteomes self-organise, i.e. to decipher the physicochemical codes and limits for protein properties and quinary interactions in vivo.