Somatic mutation in human macrophages: defining ontogeny and mechanisms of inflammatory disease

When a cell replicates, its DNA code is altered, introducing ‘somatic' mutations.  The descendants of that cell inherit new mutations, providing a molecular bar-code allowing us to track them.  I use this barcode to determine whether macrophages, a class of immune cells, are formed in the embryo, or whether they originate later, from the bone marrow.  Some critical macrophages, like microglia in the brain, may be embryonic. This could be important in understanding their role in dementia.  With ageing, somatic mutations cause the bone marrow to develop abnormalities. I aim to find out if bone marrow-derived macrophages transmit these abnormalities to distant tissues, increasing the risk of vascular disease and immune disorders.  Finally, sometimes somatic mutation activates cancer genes.  If this happens in a macrophage, an inflammatory disease may occur.  I aim to discover if this is the cause of spontaneous inflammatory diseases such as vasculitis and sarcoidosis.