One cell at a time: Uncovering how enhancers orchestrate cardiovascular fate using single-cell multi-omics (MUNSTERBERG_U26DTP)
The cardiovascular system – comprising the heart, blood, and blood vessels – is the first functional organ system to form during vertebrate development, and its correct assembly is essential for life. Cardiac progenitor cells give rise to the heart, while hematoendothelial progenitors form blood and vascular endothelium. These lineages share a common origin in the lateral plate mesoderm yet diverge through tightly regulated gene regulatory networks.
While many of the key transcription factors are known, the enhancers – non-coding DNA elements that control when and where genes are switched on – are less well understood. Mutations in these elements are increasingly linked to congenital heart and vascular defects yet identifying and functionally validating them in the complex cellular environment of the embryo remains a major challenge.
In this new and exciting PhD project, you will apply cutting-edge single-cell multi-omic approaches (scRNA-seq & scATAC-seq) to map the enhancer landscape during early cardiovascular development in the chick embryo, a tractable and image-friendly vertebrate model. You will learn advanced bioinformatics to integrate gene expression and chromatin accessibility data to predict active enhancers, reconstruct gene regulatory networks, and identify evolutionarily conserved elements.
Experimentally, you will gain skills in molecular biology to clone candidate enhancers into fluorescent reporter constructs for live imaging and use CRISPR-based perturbations to test their function in vivo. This will reveal how specific enhancers shape cell behaviour, migration, and fate decisions during heart and vessel formation.
You will join a collaborative supervisory team across UEA (Andrea Münsterberg & Gi Fay Mok) and the Earlham Institute (Iain Macaulay & Wilfried Haerty), gaining skills in developmental biology, molecular genetics, imaging, and computational biology. This multi-disciplinary project offers the opportunity to make fundamental discoveries about the genomic control of cardiovascular development – one cell at a time.
Contact a.munsterberg@uea.ac.uk or g.mok@uea.ac.uk for more information.