University of Dundee

MRC DTP: Mechanochemical modelling of cellular motion patterns in early embryos

The rapid advances in life imaging of detailed complex cell behaviours of all major cell types at the scale of amniote embryos under normal and experimentally perturbed conditions has led to an unprecedented amount of quantitative information on the cellular and tissue dynamics of early embryonic development. A major challenge is how to understand the cell-cell signalling mechanisms that coordinate a verity of complex cell behaviours such as cell division, differentiation and movement of thousands of cells and how these cell behaviours in turn feedback on signalling to result in embryo development. There is increasing evidence that besides well-established chemical signalling through diffusible and cell bound molecules, mechanical signalling mediated through cell-cell contact and mechanosensitive chemical reactions are a major component in both the short and long range coordination of these cell behaviours. Therefore, in order to understand how cell-level processes lead to tissue-scale flow patterns, it is necessary to develop a biophysical model that combines biochemical processes (i.e., cell signalling), mechanical forces and gene regulation.

The main aim of the project will to develop understanding of how cell division, intercalation and ingression events coordinate with force generation processes driven by the cytoskeletal actomyosin network to lead to the formation of the primitive streak in early chick embryos. Building on the previous work of both groups, the project will involve continuum (e.g., active gel) and discrete mechanical models (e.g., Vertex Model) of epithelial tissues extended to account for non-linear chemical feedback. Modelling will be closely informed by light-sheet microscopy imaging of transgenic chick embryos. The PhD candidate will closely work with both supervisors and gain first-hand experience in advanced biophysical modelling and large scale image data analysis. It also offers possibility to directly engage with/participate in the experimental work. This project will provide state of the art training at the interface between physics and life sciences.

Candidates with background in physics, applied mathematics or a closely related field and a keen interest to engage with life sciences are strongly encouraged to apply. Strong programming skills (MATLAB or Python and familiarity with C/C++) are essential.

Recent work from the lab can be found in the following references: 

  1. E. Rozbicki, et al., Myosin-II-mediated cell shape changes and cell intercalation contribute to primitive streak formation, Nature Cell Biology 17, 397-408 (2015).
  2. D. Barton, at al., Active vertex module for cell-resolution description of epithelial tissue mechanics. PLoS computational biology 13, e1005569 (2017).
  3. M Serra et al. Dynamic morphoskeletons in development. Proc Natl Acad Sci USA , 117 (21) 11444-11449 (2020)

Eligibility