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Cell polarity regulation in a model eukaryote

  • Full or part time
    Prof K E Sawin
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Normal cell architecture and organisation depends on internal and external cues and landmarks. Upon stress, cell organisation can also change in a coordinated way, either to generate changes in shape or to achieve homeostasis at the level of the entire cell.

Our laboratory studies eukaryotic cellular organisation, with a particular focus on the cytoskeleton and cell polarity regulation. We use the unicellular fission yeast Schizosaccharomyces pombe as a model organism, because it is amenable to combined genetics, microscopy, and biochemistry/proteomics approaches. Many of the molecular mechanisms underlying S. pombe organisation are conserved in mammalian cells.

Recently we discovered an unexpected link between stress-activated protein kinase signaling and cell polarity. Within this 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 how this affects cell-polarity regulation by stress. 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 sources of funding may be available. The Sawin lab is a vibrant, international group of PhD students and postdoctoral fellows, funded by 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: https://www.wcb.ed.ac.uk/research/sawin or http://sawin.bio.ed.ac.uk Students are welcome to contact Prof Sawin directly by email.


Funding Notes

The “Visit Website” 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 5 January 2020 at the latest.

References

Tay, Y.D., Leda, M., Spanos, C., Rappsilber, J., Goryachev, A.B., and Sawin, K.E. (2019). Fission Yeast NDR/LATS Kinase Orb6 Regulates Exocytosis via Phosphorylation of the Exocyst Complex. Cell Rep 26, 1654-1667 e1657. link

Thakur, H.C., Lynch, E.M., Borek, W.E., Bao, X.X., Ashraf, S., Zou, J., Rappsilber, J., Cook, A.G., and Sawin, K.E. (2019). Architecture of the Mto1/2 microtubule nucleation complex. bioRxiv, 754457.

Leong, S.L., Lynch, E.M., Zou, J., Tay, Y.D., Borek, W.E., Tuijtel, M.W., Rappsilber, J., and Sawin, K.E. (2019). Reconstitution of Microtubule Nucleation In Vitro Reveals Novel Roles for Mzt1. Curr Biol 29, 2199-2207 e2110.

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.

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.

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

FTE Category A staff submitted: 109.70

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

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