Equipment for Structural Biology in the School of Life Sciences at the University of Sussex. (360G-Wellcome-092933_Z_10_Z)

X-ray crystallography is the most powerful technique available for providing the detailed structural insights into biological macromolecules, from which their mechanism, specificity and regulation can be understood. To allow us to apply this approach to the study of proteins and complexes involved in human health and disease, we propose to establish a managed multi-user facility for macromolecular crystallisation, and for X-ray diffraction data collection and analysis. Formation of the crysta ls required for X-ray crystallography needs multimilligram quantities of the protein or complex under study. Insect cells infected with engineered baculoviruses expressing target genes of interest, are an effective system for large-scale production of high-quality proteins and complexes, including post-translational modifications that are essential to function. To exploit this effective approach we propose to establish a managed multi-user facility for large scale baculovirus/insect cell express ion of target proteins and complexes. Crystal structures provide the atomic detail from which the specificity of molecular interactions can be understood, but do not define the strength of those interactions, nor their kinetics. Ancillary quantitative biophysical approaches, such as calorimetry, spectroscopy and surface plasmon resonance, are therefore also required. To access these techniques we propose to establish a multi-user facility for protein interaction biophysics.