Engineering neural tube development

Do we have sufficient understanding to engineer bespoke neural tissue? To test this, we will use the developing neural tissue to establish a synthetic approach to form robust patterns of cellular organisation. This will test and extend our understanding of neural tube development and create tools to control and engineer tissue for use in synthetic applications and disease modelling. Previously we: - Developed quantitative understanding of the genomic, molecular and cellular mechanisms of neural tube development. - Established methods for the biomimetic generation of neural tissue from Embryonic Stem Cells (ESCs). - Established collaborations with physicists and computer scientists to develop data driven dynamical models. On these foundations we will develop a system for precision tissue engineering based on ESCs, re-engineered neural tube components, and multiscale models. We will: - Establish optogenetic control of extracellular signals to instruct spatial- temporal pattern formation in synthetic ESC derived neural tissue. - Generate a suite of synthetic gene regulatory elements with defined regulatory function and use these to produce novel circuits that elicit predictable responses. - Combine extracellular and intracellular modules to produce precision programmable synthetic developmental patterns of gene expression and cell fate. To guide experiments and interpret data, we will use computational simulations constrained by quantitative experimental measurements.