One cell at a time: uncovering enhancer control of blood and cardiovascular fate using single-cell multi-omics (MOK_U27DTP)

The cardiovascular system – comprising the heart, blood and blood vessels – is the first functional organ system to form during vertebrate development. Cardiac progenitor cells generate the heart, while hematoendothelial progenitors produce blood and vascular endothelium. Although these lineages share an origin in the lateral plate mesoderm, they acquire distinct identities through tightly controlled gene-regulatory programmes. Many transcription factors involved in cardiovascular development are known, but much less is understood about the enhancers that control when and where these genes are activated. Enhancers are non-coding DNA regions that direct cell-type-specific gene expression. Their disruption is increasingly associated with congenital cardiovascular and blood disorders, yet identifying functional enhancers and testing their roles in the developing embryo remain major challenges.

In this PhD, you will use single-cell multi-omics, combining gene-expression and chromatin-accessibility data, to investigate how enhancer activity changes as blood, endothelial and cardiac lineages emerge in the chick embryo. You will learn computational approaches to integrate single-cell RNA-sequencing and ATAC-sequencing data, reconstruct gene-regulatory networks and identify candidate enhancers linked to specific cell states and developmental trajectories. Particular emphasis will be placed on how hematoendothelial progenitors generate the first blood and vascular cells, with cardiac development providing an important comparison. Experimentally, you will clone candidate enhancers into fluorescent reporter constructs and visualise their activity in living embryos. CRISPR-based perturbation and motif mutagenesis will then test how selected enhancers control gene expression, cell behaviour and fate decisions in vivo.

You will join a collaborative supervisory team across UEA and the Earlham Institute, led by Dr Gi Fay Mok with Professor Andrea Münsterberg, Dr Iain Macaulay and Dr Wilfried Haerty. The project provides interdisciplinary training in developmental biology, molecular genetics, imaging, single-cell genomics and computational biology.

For further information, contact g.mok@uea.ac.uk.