Characterisation of glycan ligands recognised by collectin-11 in ischaemic kidney and development of a specific antagonistic probe

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The cells making up our tissues and organs are covered with sugar molecules. This coating normally is important in organ development and maintenance but can be a target for our immune system, causing tissue damage. We have found that blood flow disturbance to the kidney can lead to an abnormal pattern of sugars on the cell surface and this triggers inflammation through a molecule called collectin-11. Collectin-11 is a normal tissue product that acts in self defence. However, in abnormal circumstances such as when the organ is donated for transplantation, the sugar pattern can change and this can provoke inflammation and loss of function of the organ. Our aim is to identify the biochemical composition of the abnormal sugar pattern, because this will provide the key to improved treatment and diagnosis. Very simply, if we can work out how collectin-11 recognises the abnormal pattern, we can potentially mask it from collectin-11. The first steps of our research involve extracting a representative sample of the hundreds and possibly thousands of sugars (glycans) found in human kidneys after the organs have been removed from the donor. We can then screen the array of glycans to determine which ones bind strongly to collectin-11. To help us manage the complexity and scale of this procedure, we will make use of robotics to display the glycans and mix them with collectin-11. We can then examine the composition of the most interesting sugars which have strong affinity for collectin-11 and find out where and when they are expressed in kidney biopsies from patients. These studies of human tissue will not only reassure us we are on the right track, but they will help identify which patients could potentially benefit from the treatment to block the abnormal sugar pattern and prevent inflammation. A blocking agent that we are developing for this purpose will need further modification to ensure it fits like a glove over the abnormal sugar. That way the treatment will be more selective and have fewer side effects.