Molecular control of eye development: investigating a novel gene network at the root of retinogenesis

GROCOTT_U20DTP

The eye is our primary sense organ and a major conduit through which we experience the world around us. Congenital malformations that arise in the developing embryo can compromise vision, accounting for a quarter of all childhood blindness with life-long consequences. Our research uses the chick embryo to investigate how normal eye development is regulated at the molecular and cellular levels, and to uncover the causes of eye malformations. Moreover, by learning how eyes develop in the embryo we can rationally design strategies to generate them in vitro, important applications of which include disease modelling, drug development and regenerative therapies.

It is known that stem cell cultures can spontaneously self-organise to form retinas in vitro, but it is not known how they do this. This PhD project aims to investigate a Pax6 gene network that could drive selforganisation of the early retina, both in the embryo and in stem cell cultures. Pax6 was named a ‘master control gene’ for eye development, and we recently identified a network of Pax6-interacting genes with the potential to spontaneously self-organise the early retina. The project will directly test this Pax6-network by measuring key biophysical properties of its different gene products and comparing them with values predicted by computer simulations of early retinal development.

The project will develop your transferable ‘wet lab’ skills in molecular, cell, and developmental biology, and advanced imaging. You will receive rigorous training in quantitative analytical approaches, with an added opportunity to gain further skills in computational biology (computer programming, mathematical modelling; previous experience not required).

References:

– Grocott, T. et al. The Pax6 master control gene initiates spontaneous retinal development via a selforganising Turing network. bioRxiv 583807 (2019). doi:10.1101/583807

– Ali R.R., Sowden J.C. Regenerative medicine: DIY eye. Nature 472, 42-43 (2011)

– Eiraku, M. et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472, 51-56 (2011)

– Gehring, WJ. The master control gene for morphogenesis and evolution of the eye. Genes Cells 1, 11-15 (1996)