Systems Biology, Genetics, Genomics and Mathematical Biology
The Francis Crick Institute
NW7 1AA, United Kingdom
Gene regulatory networks in early development We are interested in the early stages of vertebrate development. We study this at a systems level, using a combination of experimental data and computational techniques in both Xenopus and mouse models. Most of our current work is in Xenopus: this is an ideal model system, as many hundreds of developmentally synchronised embryos can be generated from a single clutch. In addition, the early embryonic axes can be readily identified shortly after fertilisation, facilitating study of axial asymmetry and growth. The Gilchrist lab is currently a 50:50 mix of experimental and computational scientists. Embryonic development is a complex and tightly controlled process, with a remarkably precise outcome. The underlying control system is only partly understood. Typically, transcription factors regulate the expression of individual genes, and the many relationships between transcription factors and their target genes combine to make gene regulatory networks. Our aim is to elucidate these networks using molecular and computational tools developed in the last few years, that enable a systematic and large-scale approach. Our long-term goal is to be able to understand development as a series of genetic interactions which need to proceed with the correct timing and in the right location within the growing embryo. Exploring gene regulation at the maternal-zygotic transition The first major developmental hurdle for the fertilised zygote is the maternal-zygotic transition, when the embryo becomes reliant on the integrity of its own genetic material. Up to this point (termed the mid-blastula transition in Xenopus) development is regulated by maternally deposited molecules, and proceeds through a number of rapid, synchronous cleavages until the cell cycle slows dramatically with the establishment of zygotic transcription. Previously the time scales of these processes have been poorly defined. We have used next-generation sequencing data to create high-resolution gene expression profiles, and used these to explore the timing and nature of the different phases of early development.
Also involved in Dev Com ITN network of Developmental Biologists in Europe.