PhD Research Project: Epithelial morphogenesis: coordinating planar polarity and tissue mechanics.
Background: In developing cell sheets, multiple mechanisms exist to orient cells within the plane of the tissue. Such ‘planar cell polarity’ (PCP) ensures that growth and tissue structure are properly organised. Intriguingly, both secreted morphogens and mechanical forces have been implicated as orienting cues for planar polarisation. The study of cell orientation thus provides a system for dissecting the interplay between chemical and mechanical signals.
Objectives: Drosophila provides an ideal model system for dissecting these mechanisms, since it is highly amenable to genetic manipulation and has easily accessible simple tissues suitable for live imaging. We will integrate cutting-edge genetic tools, live imaging and computational modelling in an iterative manner to: (i) explore how mechanical forces influence patterning and polarity; and (ii) understand how cell division modulates tissue mechanics and coordinated cell polarity.
Experimental Approach: Detailed spatiotemporal quantitative data concerning cell shape, cell division, patterning and in vivo cell tension in developing Drosophila tissues will be generated, under normal and abnormal conditions. In particular genetically modified fly strains expressing fluorescently-tagged proteins and FRET-based tension sensors will be used, alongside in vivo laser cutting to directly probe in vivo forces. Computational models will be implemented using a software package, Chaste (www.cs.ox.ac.uk/chaste), previously developed by AF and colleagues. We will use these models to explore different assumptions about cell division and rearrangements and test their sufficiency against experimental observations.
Novelty & Timeliness: Only with the improvement of live-imaging methods, combined with genetically encoded fluorescent sensors and sophisticated computational modelling tools, is it now possible to make major advances in understanding epithelial tissue dynamics at a quantitative systems level.
Science Graduate School
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These Projects are competitive studentships based at the University of Sheffield funded by BBSRC covering:
(i) a tax-free stipend at the standard Research Council rate (~£14-£15K, to be confirmed for 2019) for 4 years
(ii) research costs, and
(iii) tuition fees at the UK/EU rate for 4 years.
Studentships are available to UK and EU students who meet the UK residency requirements. Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award. Further information on eligibility: http://www.whiterose-mechanisticbiology-dtp.ac.uk/wp-content/uploads/2018/06/studentshipeligibility.pdf .
At least a 2:1 honours degree in a relevant subject, or equivalent.