Unravelling the mechanisms of mammalian Polycomb-dependent gene repression through functional evolutionary analysis

Genes encoding components of the Polycomb gene silencing system are frequently mutated or dysregulated in human diseases. In humans, however, the Polycomb system has evolved to be extremely complex making it difficult to study. I will use "simpler" organisms called choanoflagellates, the closest unicellular relatives of animals, to investigate how the Polycomb system functioned in the ancestor of animals and to shed light on the core principles through which Polycomb silencing operates. Choanoflagellates have a much less complex set of Polycomb genes and his will make it easier to disentangle their functions. This work will reveal the underlying principles of how Polycomb silencing functions and will provide insights into how this becomes aberrant in disease as well as illuminating the core mechanisms of the system which may be targets for future therapies.