A laboratory for membrane protein structural biology

We propose a Membrane Protein laboratory (MPL) that will have as its central goals to drive the engagement in membrane protein structural biology and develop new approaches to obtain structural data for biomedical problems. Structural biology, mainly crystallography, of soluble proteins is becoming routine, in part because the community has learned what works and crucially what does not. The MPL will develop robust expression and isolation methods with the aim of screening tens of constructs for each target. Solubilization of membrane proteins requires the identification of suitable detergents which is complex, depending both on protein and subsequent technique (amphipols are excellent for EM but not crystallography). We will miniaturise and standardise approaches; only by driving down the time and cost of exploratory approaches will they become routine enough to be widely used. At the same time with the downstream analysis facilities on-site at Diamond, we will develop new approaches in EM grid preparation, crystallisation and solution preparation to get structural data rapidly from small amounts of protein. The MPL is well situated for the required interactions with the UK scientific community, Diamond Light Source, RAL central laser facility, the UK XFEL Hub, and the cryo-EM instruments at the eBIC.