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PhD Research Project: Epithelial morphogenesis: coordinating planar polarity and tissue mechanics.

Employer
Global Academy Jobs
Location
United Kingdom
Closing date
Dec 2, 2016

Job Details

Details

As an organism develops, tissues are shaped and patterned in a coordinated way. The long-standing dogma of developmental biology is that secreted proteins diffuse to form expression gradients throughout tissues thereby providing spatial cues to direct growth, fate and pattern, drawing responses from cells even at some distance from the source. More recently, studies have revealed critical roles for mechanical forces in regulating morphogenesis, however, the interplay between these two systems is poorly understood. With the advent of fast 4D live imaging, 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.

The model organism Drosophila provides an ideal system for dissecting mechanisms of morphogenesis in cell sheets, as it is highly amenable to genetic manipulation and has easily accessible simple tissues suitable for live imaging. The project will integrate cutting-edge genetic tools, advanced 4D fast live imaging and computational modelling in an iterative manner to: (i) explore how mechanical forces influence patterning and polarity; (ii) understand how cell division modulates tissue mechanics and coordinated cell polarity; and (iii) develop mathematical approaches to incorporate pattern and proliferation within existing modelling frameworks for epithelial morphogenesis.

We are looking for an enthusiastic and ambitious student to carry out this interdisciplinary project using both experimental and computational approaches. This project will be suitable for a student with a strong quantitative background (e.g. mathematics, physics, engineering or computer science) who is keen to apply their skills to a biological problem with potentially significant translational importance, or a student with a biological background but a strong interest and some skills in computational approaches. Moreover, the student will be provided with an interdisciplinary training, gaining valuable laboratory experience, particularly in high-level imaging and image analysis, as well as in mathematics and computational modelling.

Funding Notes

Applications from self-funded students or students with secured funding are also welcome.
Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD Studentship, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/bms/prospective_pg/how_to_apply
*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.
 

References

Warrington SJ, Strutt H and Strutt D. (2013) The Frizzled-dependent planar polarity pathway locally promotes E-cadherin turnover via recruitment of RhoGEF2. Development 140(5):1045-1054.

Strutt H*, Warrington, SJ* and Strutt D. (2011) Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains. Developmental Cell 20: 511-525.

Kursawe J, Brodskiy PA, Zartman JJ, Baker RE, Fletcher AG. Capabilities and Limitations of Tissue Size Control Through Passive Mechanical Forces. PLoS Comput Biol. 2015 Dec 29;11(12):e1004679.

Tetley RJ, Blanchard GB, Fletcher AG, Adams RJ, Sanson B. Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension. eLife. 2016 May 16;5:e12094.

http://www.shef.ac.uk/bms/research/strutt
http://alex-fletcher.staff.shef.ac.uk

Company

Global Academy Jobs works with over 250 universities worldwide to promote academic mobility and international research collaboration. Global problems need international solutions. Our jobs board and emails reach the academics and researchers who can help.

"The globalisation of higher education continues apace, driving in turn the ongoing development of the global knowledge economy, striving for solutions to the world’s problems and educating a next generation of leaders and contributors."

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