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  Cell polarity regulation in a model eukaryote.


   School of Biological Sciences

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  Prof K E Sawin  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Cells build and maintain their normal architecture and organisation through internal and external cues and landmarks. At the same time, cell organisation can change in a coordinated way in response to external stresses, either to effect changes in architecture or to achieve homeostasis at the level of the entire cell.

Our laboratory studies eukaryotic cellular organisation, with a particular focus on the microtubule and actin cytoskeleton systems and cell polarity regulation. We use the unicellular fission yeast Schizosaccharomyces pombe as a model organism, because of its decreased complexity relative to mammalian cells, as well as its amenability to combined genetics, microscopy, and biochemistry/proteomics approaches.

Recently we discovered an unexpected link between stress-activated protein kinase signaling and cell polarity. Within this general area, several related PhD projects are possible. We are currently identifying the targets of stress-activated protein kinases that regulate cell polarity. A PhD project in this area will focus on newly identified targets, mutating their phosphorylation sites, and investigating effects on cell-polarity regulation by signaling. A PhD project in a related area will address how changes in the cytoskeleton can evoke a stress response, a major unexplored area. Another PhD project will develop new fluorescence probes and techniques to investigate how stress-activated kinases are activated in non-stress conditions.

We have also identified a novel cell-polarity landmark system in fission yeast, in which a long-lived protein complex inserted in the plasma membrane serves as a “bookmark” for polarised growth in the subsequent cell cycle. We are now interested in determining how this novel landmark interacts with the core cell-polarity module and the cytoskeleton. A PhD project in this area will focus on identification of “downstream” effectors of this novel landmark, using a combination of proteomics, genetics, and fluorescence microscopy.

All PhD projects in the lab are interdisciplinary and include: classical and molecular genetics (including genome engineering); live-cell microscopy of fluorescent-tagged proteins; and biochemistry and mass spectrometry/proteomic methods. We have state-of-the art facilities for microscopy, mass spectrometry, protein purification, and genetic sequencing. A PhD project involving yeast genetics/cell biology/biochemistry is an excellent way to begin a scientific research career, because many different methods are learned and applied in the context of rigorous hypothesis-driven research, and hypotheses are constantly challenged and logically refined by new results.

In addition to UK and EU students, international students are encouraged to apply, as special funding may be available, depending on qualifications. The Sawin lab is a vibrant and international group of PhD students and postdoctoral fellows, and we have recently received renewed funding from the Wellcome Trust. We have close collaborations with other researchers in Edinburgh and beyond, and joint lab meetings with other research groups in Edinburgh. For further information about the laboratory, visit http://sawin.bio.ed.ac.uk/ , http://www.wcb.ed.ac.uk/research/sawin. Students are welcome to contact Prof Sawin directly by email.

Funding Notes

The “Apply online” button on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.

If you would like us to consider you for one of our scholarships you must apply by 12 noon on 13 December 2018 at the latest.

References

Mutavchiev, D.R., Leda, M., and Sawin, K.E. (2016). Remodeling of the Fission Yeast Cdc42 Cell-Polarity Module via the Sty1 p38 Stress-Activated Protein Kinase Pathway. Curr Biol 26, 2921-2928. link

Tay, Y.D., Leda, M., Goryachev, A.B., and Sawin, K.E. (2018). Local and global Cdc42 guanine nucleotide exchange factors for fission yeast cell polarity are coordinated by microtubules and the Tea1-Tea4-Pom1 axis. J Cell Sci 131, jcs216580. link

Bao, X.X., Spanos, C., Kojidani, T., Lynch, E.M., Rappsilber, J., Hiraoka, Y., Haraguchi, T., and Sawin, K.E. (2018). Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore. Elife 7, e33465. link

Tay, Y.D., Leda, M., Spanos, C., Rappsilber, J., Goryachev, A.B., and Sawin, K.E. (2018). Fission yeast NDR/LATS kinase Orb6 regulates exocytosis via phosphorylation of exocyst complex. bioRxiv preprint https://doi.org/10.1101/291468 link.


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