Project facts Principal investigator: Attila Csikasz-Nagy Funding agency: Human Frontiers Science Program Duration: 36 months Starting date: 1-Nov-2009 USD: 350.000 Contact person:  Attila Csikasz-Nagy

Background & Hypotheses
The establishment and maintenance of specialized plasma membrane and cytoplasmic domains leading to growth at restricted regions of the cell cortex is fundamental to the form and function of many polarized cell types, ranging from yeasts to neurons. It results from the concerted action of cytoskeletal components and a variety of highly evolutionarily conserved ‘polarity factors’. Although substantial progress has been made in identifying factors and describing their individual modes of action, how their collective (‘systemic’) interactions mediate with precision the initiation, maintenance and termination of localized cell growth and convey plasticity and robustness to the polarized growth process remains, even for the simplest cells, poorly understood.

Objectives
Our objective is to carry out the most detailed quantitative study of the ‘systemic’ regulation of polarized cell growth to date, using cells of the fission yeast Schizosaccharomyces pombe. The fission yeast with its relative genomic simplicity, genetic tractability, uniform size and shape, and extremely well-characterized and comparatively simple polarization machinery, is ideal for this study.

Research plan
A) Which polarity factors and factor interactions are sufficient to generate localized areas of sustained cell growth: we will identify and quantify, among known fission yeast polarity factors of the ‘Tea1 cluster’ and the ‘Cdc42 cluster’, the ‘core’ of factors and factor interactions that suffice to give rise to localized areas of sustainable polarized growth.
 B) How the localization, initiation, maintenance and termination of polarized growth are regulated in space and in time: we will investigate how the ‘core’ factor network together with the cytoskeleton and the cell cycle machinery can define the position and timing of growth zone assembly.
Approaches
For every project and subproject, we will use a combination of genetics, quantitative microscopy and computer modelling and work iteratively between those approaches.
Significance of anticipated results
By this approach we hope to gain novel insights on how polarized cell growth is fine-tuned in fission yeast, and to significantly advance our fundamental understanding of general design principles of cell polarization relevant to other eukaryotic cells.

Partners

Rafael Edgardo  Carazo Salas - ETH Zuerich (from Feb 1, 2010: University of Cambridge)

Masamitsu Sato - University of Tokyo