Spatial regulation of cell polarisation

• Applicant: Dr. Björn Hegemann
• Subject Area: Biochemistry
• Term: from 2011 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 203137530

Cell polarisation is fundamental for many biological processes. Research in a variety of systems, e.g. in neutrophil migration, axon formation and yeast mating has identified a number of conserved molecular components directing polarisation towards an external guidance cue. The molecular mechanisms of how these polarity proteins detect the direction of the external cue and how this directional information is then transformed into a spatially restricted intracellular signal that establishes polarity towards the cue is not understood. Theoretical models suggest that positive and negative feedback loops are required to establish cell polarisation towards an external cue. The mitogen-activated protein kinase (MAPK) Fus3 in yeast is a regulator of signalling feedback mechanisms. A number of previous observations, including my own preliminary data, suggest that Fus3 might be directly involved in establishing and maintaining polarisation towards the pheromone gradient.In my proposed project I aim to test which molecular mechanisms establish polarity on a molecular level and how Fus3 activity regulates polarisation. I will use live-cell imaging in microfluidic gradient chips to precisely measure the kinetics of protein polarisation towards the pheromone gradient and to test how Fus3 activity influences polarity establishment. In addition I will employ quantitative proteomics to characterise dynamic changes in polarity protein complexes and phosphorylation sites upon polarity establishment and in dependence on Fus3 activity.This study is expected to generate important insights into how spatial information is molecularly encoded and transmitted in yeast cell polarisation. Because the yeast signalling modules are well-conserved, these results will help understanding how other polarity systems and spatially controlled signalling systems are regulated on the molecular level.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Matthias Peter