Project Reference: TRG27-SCI-RT1

Project title: Quantifying Mammalian Heart development: Defining the emergence of congenital heart defects.

Project outline

The mammalian four chambered heart forms through tightly coordinated cellular differentiation and extensive morphogenetic remodelling, all while functioning as a contractile organ that sustains the developing embryo. Congenital heart defects (CHDs) are the most common birth defect, occurring in at least 1 in 125 births, yet their developmental origins remain poorly understood. In humans, the heart is most vulnerable to malformation between 3–7 weeks of gestation — the period during which cardiac morphogenesis initiates and the most dramatic structural rearrangements occur.

This project, in collaboration with the Cambridge Image Analysis group led by Professor Carola Bibiane Schönlieb, aims to quantitatively define mammalian heart development by generating a standardised model of “normal” cardiac morphogenesis in the mouse and human. Using whole mount confocal and lightsheet microscopy, volumetric datasets will be acquired across key developmental stages, enabling high resolution reconstruction of cardiac structures over time. These datasets will be analyzed to extract morphological metrics and developmental trajectories. This framework will then be applied to hearts from novel transgenic models exhibiting mutant phenotypes, allowing us to quantify how congenital heart defects arise during embryonic development. By integrating morphological phenotyping with transcriptomic modalities such as single cell RNA sequencing and spatial transcriptomics, this project will generate new mechanistic insight into the cellular and molecular origins of CHDs.

Principal Supervisor

Dr Richard Tyser

Email address: rt593@cam.ac.uk

Department / Partner Institute: Cambridge Stem Cell Institute

Website: https://www.stemcells.cam.ac.uk/people/pi/tyser

BBSRC strategic theme

Understanding the rules of life