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The adaptive immune system employs stochastic somatic V(D)J recombination to generate a diverse T-cell receptor repertoire capable of recognising unknown foreign antigens. For this strategy to succeed, T-cells acquiring self-reactive receptors must be deleted or directed to a regulatory fate. In large part, T-cell selection is centrally guided by thymic epithelial cells (TEC) which challenge naïve T-cells with a near-complete molecular mirror of self-antigens. This unusual ability of TEC to promiscuously express virtually all protein coding genes is poorly understood but depends on the autoimmune regulator, Aire, a factor essential for the avoidance of autoimmunity. In collaborative work with Professors’ Georg Hollander and Chris Ponting, we are using single cell genomics approaches to study the mechanics of promiscuous gene expression in TEC. This work is funded by a Wellcome Trust Strategic Award