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Mechanistic mathematical / computational modelling of integrin signalling

  • Full or part time
    Dr N Savage
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Regulation of adhesion dynamics and mechanosensation controls cell migration, microenvironment remodelling and global cell fate decisions. We have evidence that syndecan-4 (Syn4) integrates adhesion and growth factor receptor signals to control integrin trafficking and force transmission. Adhesion and growth factor receptor signals impact upon a complex syndecan-4 phospho-regulatory network co-ordinating where and when specific integrins are engaged.

In an effort to understand this complexity, we have generated a mathematical model, incorporating data from extensive analyses of Syn4 phosphorylation, binding partners, Arf6 activity and integrin recycling. We will employ a multi-disciplinary approach to refine our mathematical model and determine the direct contribution of mechanical inputs, integrin engagement, growth factor receptors and key kinases and phosphatases.

Successful completion of this project will greatly enhance our understanding of how growth factor receptor and adhesion receptor signals are integrated to dynamically control mechanical force transmission and microenvironmental remodelling.

The student will work closely with both Drs Savage and Morgan. They will be trained in using mathematics and computation to build mathematical/computational models of the system under question. The student will use their models to predict biological mechanism, and help design experiments to test the hypothesised mechanisms. The student may also have the opportunity to work in the Morgan Lab, this depends on both funding and the student’s interest.

Applicants should have a degree in mathematics, physics or computer science. Students with other degrees must have strong evidence of interest and achievement in mathematics and/or computation.

Informal enquiries are welcome.

Funding Notes

The project is open to both European/UK and International students. It is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project.

Assistance will be given to those who are applying to international funding schemes.

The successful applicant will be expected to provide the funding for tuition fees and living expenses.

A fee bursary may be available for well qualified and motivated applicants.

Details of costs can be found on the University website:
View Website

References

Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling.
Mark R. Morgan, Hellyeh Hamidi, Mark D. Bass, Stacey Warwood, Christoph Ballestrem, and Martin J. Humphries. Developmental Cell 24 (2013).

Inhibitory GEF Phosphorylation Provides Negative Feedback in the Yeast Polarity Circuit (Journal article)
Kuo, C. -C., Savage, N. S., Chen, H., Wu, C. -F., Zyla, T. R., & Lew, D. J. (2014). Inhibitory GEF Phosphorylation Provides Negative Feedback in the Yeast Polarity Circuit. CURRENT BIOLOGY, 24(7), 753-759. doi:10.1016/j.cub.2014.02.024

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