Work in this theme is directed at uncovering the molecular function of multi-subunit macromolecular complexes, particularly those involved in cell-signalling, protein-nucleic acid transactions, and assembly-line natural product biosynthesis. The engineering and directed evolution of enzyme catalytic function is another focus. Extensive collaboration occurs with researchers in other themes, notably molecular cell biology, and with the Department of Chemistry, and there is increasing emphasis on integrative approaches to structural studies.
Recent work in this theme includes structural studies using NMR (nuclear magnetic resonance) spectroscopy, Xray crystallography and computational modelling. Examples using NMR include the first high resolution solution structure of a 7-helix trans-membrane receptor. Crystallography has been used to demonstrate how bacterial small RNAs guide RNase E to degrade target RNAs. Modelling techniques used with NMR data have been adapted for use with single-cell chromatin conformation datasets to generate the first 3D models of chromosomal interactions in mammalian cell nuclei.
Important on-going programmes include fragment-based drug discovery, engineered biosynthesis of novel antibiotics and related natural products, in vitro enzyme evolution using microdroplet compartmentalization, super-resolution fluorescence microscopy to study the structure/assembly of protein complexes in live cells at near molecular resolution.
Future plans include increasing the use of cryo EM (electron microscopy), and fluorescence and correlative microscopies for the study of macromolecular assemblies. We will build on existing strengths in molecular enzymology and enzyme engineering to play a leading part in Synthetic Biology across the University, which has announced a new strategic initiative in this area.