SciLifeLab The Svedberg seminar series 2014-06-16


Paul Flicek

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

Paul Flicek is a Team Leader and Senior Scientist of the European Molecular Biology Laboratory and leads the Vertebrate Genomics Team at the European Bioinformatics Institute (EMBL’s Hinxton Outstation) near Cambridge, England. Paul is currently head of the Ensembl project and has overall strategic responsibility for EBI’s resources focused on Genes, Genomes and Variation. Paul’s first degree is in Physics from Drake University and he worked for four years as a medical health physicist and active duty army officer at Walter Reed Medical Center in Washington, DC, before moving to St. Louis and received a DSc in Biomedical Engineering from Washington University in addition to an MSc in Computer Science. He originally joined the EBI as a postdoc with Ewan Birney.

Paul’s research is focused on comparative regulatory genomics and the evolution of transcriptional regulation. He is also interested in the large-scale infrastructure required for modern bioinformatics including storage and access methods for high throughput sequencing data. He has played a role in a number of major international projects including ENCODE and the mouse, chicken, and gorilla genome projects.

Regulatory Evolution in Mammals

Although both tissue level function and tissue level gene expression are largely conserved across mammals, several studies have shown that the binding locations of tissue-specific transcription factors change rapidly. To understand and characterise this phenomenon we have created maps of transcription factor binding and histone modification in liver and other tissues for nearly 40 species covering an evolutionary range from human to chicken, with additional focus on the primate and rodent clades. The latter dataset enabled us to characterise the first evolutionary steps in mammalian regulatory change and demonstrated that cooperative binding among factors is a significant factor in the stability of transcriptional regulation. By connecting changes in transcription factor binding to underlying changes in the genome sequence, we show that binding preferences are almost completely unchanged over evolutionary time and that most binding changes initially occur without any change to the DNA sequence in the transcription factor binding motif. Finally, in comparison to the tissue-specific factors, the ubiquitously expressed CTCF protein shows extraordinary evolutionary stability at a large number of binding sites, which are defined at least partly by ancient retrotransposon activity.

Host: Jan Komorowski