Research Topics

The core promoter is a DNA sequence, which is required for recruitment of general transcription factors and provide the platform for Polymerase II transcription. Promoters come in many shapes and sizes and contribute to transcription regulation and serve as an integration point for diverse signals conveyed by cis regulatory elements such as enhancers. The diversity of core promoter architectures with distinct transcription initiation profiles in vertebrate genomes points at an unexplained regulatory level. Despite of decades of study, we are still unable to clearly define the DNA sequences, which determine where and how Polymerase II initiates transcription. We combine genomics approaches together with functional studies in an embryo and organoid models to understand promoter level gene regulation during vertebrate development and tumourigenesis. We have recently found how transcription initiation control can impact on how the transcribed mRNAs are processed and translated into protein. We explore the interplay between transcription control and mRNA fate control in development tumorigenesis and injury-induced regeneration. We apply bulk and single cell genomics technologies (e.g. CAGE-seq, ATAC-seq, ChIP-seq, SLAM-seq etc), targeted genetic manipulation, transgenesis and 4D imaging technologies. 

Cis-regulatory organisation of developmental gene regulation 

Core promoters and their interaction with cis regulatory modules such as enhancers regulate spatio-temporal dynamics of gene expression and explain not only lineage and tissue specificity but also cell to cell variation of gene expression. The aberration of transcription regulation of genes can lead to congenital and multifactorial diseases. Large-scale genomics programmes such as ENCODE and FANTOFAM resulted in prediction of previously unanticipated density of functional elements of the human genome. These predictions raise the need for understanding the regulatory grammar of cis regulatory element organisation and to validate predicted functional variation. We are use zebrafish and exploit its transparent, externally developing embryo in exploring the semantic rules of enhancer organisation of developmental regulator genes, which are highly conserved among vertebrates. We use genomics technologies to map regulatory element function and transgenic reporters for validating cis-regulatory functions of enhancer candidates associated with congenital and multifactorial diseases.