https://www2.mrc-lmb.cam.ac.uk/group-leaders/H-to-M/kate-mcdole/
The McDole lab seeks to understand how complex 3D structures in the embryo are sculpted from initially homogenous cell populations. For example, how does an intricate, functional organ such as a beating heart arise from a ball of cells? How do tubes involute and tissues fold, and what are the physical forces that drive these shape changes? Furthermore, how are these physical forces coupled with changes in cell shape, behaviour, and gene expression to give rise to changes in tissue architecture?
To address these questions, we use the early mouse embryo as its size, similarities to human development, and ease of accessibility make it an ideal system to study how early organs and tissues take shape. We use advanced light-sheet microscopy to visualize development real-time, coupled with genetic manipulation and biophysics along with advanced computational analysis, to measure and model embryo development quantitatively.
One of the earliest organogenesis events in the mouse embryo is the development of the foregut pocket, or the primitive gut tube. This structure is essential for the development of critical organ systems such as the lungs and liver, yet its formation is poorly understood. Using live-imaging we have for the first time been able to visualize foregut involution in unprecedented detail, and have observed it to be a highly mechanical process that involves the single-cell layered endoderm suddenly and dramatically breaking symmetry to form a deep and elongating pocket from the surface of the embryo.
Opportunities for PhD projects include 1) using live-imaging data to generate quantitative measurements with the goal of building a computational model of foregut involution and 2) investigating the role of the cytoskeleton and cellular/tissue behaviours in foregut formation.
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