The general interest underlying this project is the way in which complement factor H (CFH) associates with host cell surfaces during immunity, and how this is altered in conditions such as AMD (age-related macular degeneration, a common blindness disease) and aHUS (atypical haemolytic uraemic syndrome, a renal failure condition affecting young children). CFH interacts with complement C3b, heparan sulphate and C-reactive protein (CRP). An understanding of the way in which this large regulatory protein interacts with its CRP ligand may lead to new insights into AMD and aHUS, key biomarkers for AMD and aHUS, and novel therapeutic strategies. This specific project will define the structure of two CFH complexes with CRP using deuteration and contrast variation by SANS. We already have an extensive track record of publications of the CFH interactions with heparan sulphate, C3u/C3b and CRP. We will also study these interactions using X-ray scattering at ESRF, making use of this and other PSB platforms, and analytical ultracentrifugation and surface plasmon resonance at UCL. Data interpretation will be carried out using constrained molecular modelling at UCL.