500 million years in the life of a regulatory element.
25/03/2014 - Room Garden Room at 14:00 - External Seminar
(National Institute of Medical Research, MRC)
Despite the availability of hundreds of organisms’ genomes, and thousands of personal genomes, a majority of research effort still remains at the level of the coding sequence. This ascertainment bias has a snowball effect, resulting in an increasingly large void between our knowledge of coding sequences, and of non-coding sequences. Projects such as ENCODE valiantly seek to redress the balance, but most large projects are, by definition, much more effective at annotating than they are at understanding underlying mechanisms. Our knowledge of how genomic sequences direct gene regulation remains relatively poor, and whilst the use of high throughput approaches have helped to identify individual sites, we have yet to grasp the subtleties of regulatory syntax and grammar in complex genomes. Hence, the majority of personal genome sequencing in humans is at the level of the exome, perpetuating the bias in coding sequence analysis.
My lab focuses on a set of unusually tractable regulatory sequences. Easily identifiable and associated with specific regulatory networks orchestrating early vertebrate development, we chart their unusual evolutionary history, study their variation in the human population and speculate on their role in human genetic disease. We also use mutational de-construction to understand the regulatory code of such elements in zebrafish embryos, and are interested in their roles in defining specific chromatin architectures during development.