Structural Biology
The Structural Biology Research group (Professor Trevor Greenhough, Dr Annette Shrive) aims to characterise the molecular mechanisms by which molecules of the innate immune system recognise and bind to their natural targets and effect clearance through interaction with components of immune system pathways.
This structural immunology includes ligand/pathogen recognition by the pentraxins CRP and SAP from human and a variety of other sources including Limulus, rat and fish; by collectins including hSP-D, SP-A, CL-46 and conglutinin and by other proteins targeted by our collaborators for study. Of particular interest in the group is the pathogen-host interaction, with a particular emphasis on humans and mammals but also extending through to fish and to plants. In addition to crystallography, our structural investigations utilise complementary techniques, both in-house and with collaborators, including SRCD, cryoEM, mass spectrometry, carbohydrate-type ligand manipulation and analysis and clinical measurement
Human lung surfactant protein D (hSP-D) can directly interact with carbohydrate residues on pulmonary pathogens and allergens, stimulate immune cells, and manipulate cytokine and chemokine profiles during the immune response in lungs. The high resolution crystal structures, both native and ligand bound, of a therapeutically active recombinant fragment of SP-D define the fine detail of the mode and nature of carbohydrate recognition and provide insights into how a small fragment of human SP-D can bind to whole pathogens and at the same time recruit and engage effector cells and molecules of humoral immunity. Particular current emphasis (in collaboration with University of Southampton and MRC Mammalian Genetics Unit Harwell) is on recognition of native and mutant strains of bacterial lipopolysaccharide and is complemented by in-house collaborations on carbohydrate analysis and manipulation with Dr Mark Skidmore and Dr Gavin Miller.
