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Mechanisms of microtubule organization by cell-cell adhesion in epithelial cells.

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

Project Description

The correct organization of the microtubule cytoskeleton is critical for the survival and normal function of cells in a multicellular organism. The microtubules enable intracellular vesicles and organelles to be transported and delivered to places where they are required, and in amounts needed for normal cell functions. In differentiated epithelial cells, organization of microtubules differs from the text-book image: instead of all microtubules being anchored at centrosomes by their minus ends, a population of microtubules is anchored by their minus ends at sites of cell-cell contacts on the plasma membrane. These microtubules run parallel to the cell apex and form an apical network, which is in turn important for correct distribution of cell-cell adhesion components. We use a simple model organism, the fruit fly Drosophila melanogaster, to study the organization and function of the microtubule cytoskeleton in epithelial cells. Recently, we discovered that this organization is largely influenced by the response of growing microtubules to the geometric constraints of the cell. This organization is highly reproducible between cells and different genotypes, and is insensitive to any perturbation of microtubule dynamics, number, or interaction. The only other factor, which could account for this phenomenon, is the distribution of their minus ends at sites of cell-cell contacts on the plasma membrane.

The overall aim of this project is to understand how microtubule minus ends are localized to sites of cell-cell contacts in epithelial cells. The specific objectives of the project are:
1. To identify proteins which recruit minus ends of microtubules to sites of cell-cell contacts;
2. To determine how these proteins interact with microtubule minus ends;
3. To discover the roles of correct microtubule minus ends localization on the cell and tissue levels.
During this project the student will receive training in a wide range of techniques including: molecular biology (generation of Drosophila transgenic and mutant lines using CRISPR/Cas9), state-of-art microscopy (FRAP, live imaging, super-resolution) and computational analytical approaches. Altogether, the outcome of this project will yield fundamental knowledge about the regulation of cell-cell adhesion, which will be relevant to human biology and disease.

We encourage any student who might be interested in the project to contact Dr Natalia Bulgakova () to discuss the project details.
Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.

Funding Notes

Awaiting funding decision and self-funded student are welcome to contact the supervisor to discuss the studentship opportunity.

Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: View Website

*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

• Gomez, J. M., Chumakova L., Bulgakova N. A., & Brown, N. H. (2016). Microtubule organization is determined by the shape of epithelial cells. Nature Communications, 7, 13172 http://doi.org/10.1038/ncomms13172
• Bulgakova, N. A., Grigoriev, I., Yap, A. S., Akhmanova, A., & Brown, N. H. (2013). Dynamic microtubules produce an asymmetric E-cadherin-Bazooka complex to maintain segment boundaries. The Journal of Cell Biology, 201(6), 887–901. http://doi.org/10.1083/jcb.201211159
• https://bulgakova.group.shef.ac.uk/

Related Subjects

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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