Eukaryotic cell polarity regulation and its regulation by stress

Cell architecture and organisation depends on spatial cues and landmarks, which can be both internal and external. Upon stress, cell organisation often changes in a coordinated way, either to produce changes in cell shape or to provide homeostasis at the whole-cell level.

 Our laboratory studies eukaryotic cellular organisation under normal and stress conditions, with a particular focus on the cytoskeleton and cell polarity regulation. As a model eukaryotic cell, we use the unicellular fission yeast Schizosaccharomyces pombe, 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 a novel link between stress-activated protein kinase signalling and cell polarity. Several related PhD projects are possible within this area. We are currently identifying the targets of stress-activated protein kinases that regulate cell polarity. A PhD project here 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 different stimuli, including 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 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.

 The Sawin lab is a vibrant, international group of PhD students and postdoctoral fellows and is currently 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 Interested students are welcome to contact Prof Sawin directly by email.

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