Using genome-wide data to model signalling-responsive gene regulatory networks

The formation of a fully functional organism during embryonic development is primarily coordinated and controlled by extra-cellular signalling modulators and regulators of gene expression. A fascinating aspect of embryonic development is that the timing of how different cells form is always the same. The reason for this synchrony is that all information for our body plan is encoded in our DNA, which contains instructions on when our genes should be expressed and when they should be silent. Moreover, developing cells communicate via signals to synchronise their development and activate genes to produce proteins, called transcription factors which can "read" the genetic code. These factors work together with many other proteins to ensure that genes are expressed in the right cell and at the right time. However, how chromatin structure, transcription factors and signals work together to properly regulate gene expression is unclear. To answer this question, we will use an in vitro differentiation system that mimics normal development in vitro. We will use cell lines that carry transgenes that are activated at defined time points in development and elucidate which factors are responsible for its activation and how they respond to signals. However, we will not just look at one gene, but at all of them and therefore the project is a collaboration between wet-lab scientists and bioinformaticians. We will use computational biology methods to answer the fundamental question of how the balance and timing of gene expression are controlled in development.