Joint funding with the Francis Crick Institute for a BHF-Crick Early Career Group Leader Programme: Design principles of heart morphogenesis: forces and fate

This is a jointly funded BHF-Crick Early Career Group Leader Programme in fields of broad relevance to cardiovascular research at the Francis Crick Institute.

The proposal aims to appoint 3 Early Career Leaders for up to 12 (6 + 6) years, subject to successful renewal in year 6, with the first recruitment beginning in autumn 2018.

Individual support will include a competitive salary and 4-5 core funded posts working in high-quality well-equipped laboratory space.

The Committee approved, in principle, a contribution of up to £2,064,194 for each award towards an estimated maximum total cost for each of £4,128,388 (50% BHF: 50% Crick) over 12-years.

However, they agreed that a rigorous progress review with full BHF involvement should take place at the mid-point of the first 6-year appointment.

The central aim of this work is to understand how simpler structures like a sheet of cells generate intricate 3-D architecture of organs using a well-suited model system – the developing zebrafish heart.

A critical step during vertebrate heart development is trabeculation, during which a primitive heart transforms from a simple epithelium to a complex topological structure consisting of distinct cell types.

Trabeculation defects cause cardiomyopathies and embryonic lethality, yet we don’t know how trabecular cells are specified during heart development.

Integrating cell biology, developmental biology and biophysics, this work will deconstruct the design principles of heart morphogenesis across length scales – from cells to tissues to organ.

Taking advantages of optically and genetically amenable zebrafish embryos, this project will analyse the morphological changes across time and space, as it happens, and dissect mechanical, molecular and geometric interactions that transforms the myocardial wall from a simple epithelium into a highly patterned tissue.

The outcomes from this work will advance our understanding of etiology of cardiac defects, thus facilitating the diagnosis and discovery of potential therapies.