About the Project
How does the heart form? Despite the large array of adult heart morphologies across nature, the initial heart vessel typically forms as a simple tubular structure. Further, the genetic network underlying the specification of the early embryonic heart is highly conserved across species.
In this project, we will use the power of human-derived organoid systems (coined cardioids, developed in the Simoes lab) and live imaging to unravel the fundamental mechanical and genetic mechanisms driving the formation of the initial heart vessel. What are the mechanical processes building the first heart structures, such as the lumen?
The first aim will be to develop imaging approaches to enable live imaging of the cardioids. This will involve using a range of microscopes (spinning disc, 2-photon, light-sheet). Combined with advanced image analysis methodologies, this exciting approach will enable unprecedented insight into the dynamics of the formation of the initial heart structure.
The project will explore which mechanical components (e.g., cell cytoskeleton, filopodia, actin, microtubules) are essential in building the early heart vessel. We will initially focus on identifying how perturbations to, for example, cadherins, alter the dynamics of heart lumen formation. The student will build the first dynamic atlas of the processes underlying the formation of the very first human heart structures. Importantly, we will link this to genomic information from Dr Simōes lab. What are the processes driving formation of the differentiated heart structures? Can we find signatures of feedback between mechanical and genetic processes?
This project is truly interdisciplinary, ideally suited for either (a) a trained biologist interested in developing their expertise in quantitative approaches or (b) a physicist or engineer interested in applying the latest microscopy approaches to important biological systems.
