Project Title: Understanding mechanisms of cell-cell communication that lead to coordinated cell polarisation during morphogenesis

Supervisor: Professor David Strutt (BMS and CDBG)

Application deadline: Friday 14 December 2012.

Project Description:

Tissue morphogenesis, repair and regeneration requires cells to communicate and coordinate their behaviours. Major pathways involved are the Wnt/Frizzled and Fat/Dachsous planar polarity pathways that mediate polarised cell signalling in epithelia sheets. Loss of their activity leads to a variety of developmental abnormalities in animal models such as failure of neural tube closure, cleft palates and heart defects, as well as deficits in wound healing and failure to repair kidney damage resulting in polycystic tubules. Mechanisms by which the planar polarity pathways function are poorly understood.

The project will involve dissection of pathway activity in the well-established model Drosophila, focusing on understanding the post-translational modifications that modulate the interactions between the transmembrane and cytoplasmic planar polarity proteins. Modifications and the responsible factors will be identified through genetic and biochemical techniques, and the significance for tissue patterning assayed in vivo using transgenic animals.

References:

• Strutt, H., Warrington, S.J. and Strutt, D. (2011)
  Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains.
  Developmental Cell 20: 511-525.
• Brittle, A., Repiso, A., Casal, J., Lawrence, P.A. and Strutt, D. (2010)
  Four-jointed modulates growth and planar polarity by reducing the affinity of Dachsous for Fat.
  Current Biology 20: 803-810.
• Strutt, H. and Strutt, D. (2008)
  Differential Stability of Flamingo Protein Complexes Underlies the Establishment of Planar Polarity.
  Current Biology 18: 1555-1564.

Contact Details:

David Strutt

http://cdbg.shef.ac.uk/research/strutt/

Email: d.strutt@sheffield.ac.uk