An integrated experimental and computational model of tissue regeneration and repair

Supervisors: Martin Collinson, Silke Henkes

Project description:

The corneal surface, our ‘window on the world’ is maintained by a balance of stem cell activity, cell migration across the eye, and cell loss by abrasion.  Failure of this process, after disease, injury, or surgery (e.g. corneal transplants and LASIK) can lead to degenerative corneal blindness. We have constructed an ‘active matter’ mathematical reconstruction of the corneal surface that may be able to faithfully recapitulate normal pattern of cell migration across the eye. To test whether this is the case and develop the model, the purpose of this project is to produce reporter mice and cells that can be used to visualise patterns of cell flow across the eye and in other vertebrate tissues.   Cas9/CRISPR will be used to generate reporter and knockout mice and cells in which core polarity proteins such as Frizzled-6 and Vangl2 are fluorescently tagged in vivo, to mark the leading and trailing edges of cells. Cell behaviour will be assayed by high resolution confocal imaging and we will be able to draw ‘flow maps’ of cell migration in vivo to compare to those generated in silico and refine the mathematical model. The student will then use these data to generate testable predictions in silico about how cell migration may be perturbed by injury, surgery or disease.

The student will be trained in data analysis and advanced imaging techniques, together with programming and software development. In vivo training in surgery will be core to the project. In addition to the fundamental nature of the research, the reporter mice will be important to many other labs studying cell polarity in mammals and the project will develop and distribute them as tools freely to these labs.  This is an interdisciplinary, bioscience-based project that will generate new understanding of how cells ‘see’ and respond to their environment to generate biologically fundamental processes of directed cell migration and polarity.

References:

Collinson, J. M., et al. (2002). Clonal analysis of patterns of growth, stem cell activity and cell movement during the development and maintenance of the murine corneal epithelium. Dev. Dyn. 224, 432-440.
DOI: http://doi:10.1002/dvdy.10124

R. Sknepnek and S. Henkes (2015) Active Swarms on a Sphere, PRE 91, (2015)
Physical Review. E, Statistical, Nonlinear and Soft Matter Physics, 91: 022306
DOI: https://doi.org/10.1103/PhysRevE.91.022306

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