The regulation of the cell cycle transitions in eukaryotes.
The Lopez-Aviles Group. Photo: UiO
The Lopez-Aviles group studies the mechanisms controlling progression through the cell cycle. More specifically, we focus on the study of mitotic exit and the involvement of protein phosphatases in this transition, using the fission yeast Schizosaccharomyces pombe as a model organism (relevant background information).
We aim to answer the following questions:
- What phosphatase(s) regulate cdk inactivation and exit from mitosis?
- What brings about the activation/inactivation of the phosphatase(s) so that it displays switch-like behaviour?
- What are the cues that allow its timely and coordinated regulation?
- How does this phosphatase impinge on mitotic exit progression?
- To identify the mitotic exit phosphatase(s) in S. pombe
- To study mitotic substrates (e.g., Cdk1)
- To investigate the factors that affect the timely activation of mitotic exit phosphatase(s)
- To generate a mathematical model that reproduces our observations and that allows us to predict the cell behavior in mutant situations or in the presence of external insults
- To apply our findings to other situations in the cell that require cdk inactivation (e.g., cell differentiation)
We use a combination of classical genetic and cell biology techniques:
- Generation of conditional alleles, gene tagging, gene deletion and overexpression studies
- Genetic crosses, tetrad dissection and study of genetic interactions
- Multicopy suppressor screens of mutant situations
- Flow cytometry analysis
- Cell microscopy in fixed and living cells
- Molecular cloning
- Protein analysis by western blot
- Kinase and phosphatase assays
- Comparative proteomic and phosphoproteomic studies
- Uhlmann, F. Bouchoux C and Lopez-Aviles, S. (2011). A quantitative model for Cdk control of the cell cycle, revisited. Phil. Trans. R. Soc. B (in press)
- Lopez-Aviles, S., and Uhlmann, F. (2010). Cell cycle: the art of multi-tasking. Curr Biol 20, R101-103.
- Kapuy, O., He, E., Lopez-Aviles, S., Uhlmann, F., Tyson, J.J., and Novak, B. (2009). System-level feedbacks control cell cycle progression. FEBS Lett 583, 3992-3998.
- Lopez-Aviles, S., Kapuy, O., Novak, B., and Uhlmann, F. (2009). Irreversibility of mitotic exit is the consequence of systems-level feedback. Nature 459, 592-595.
- Grande, M., Lambea, E., Fajardo, A., Lopez-Aviles, S., Kellogg, D., and Aligue, R. (2008). Crosstalk between Nap1 protein and Cds1 checkpoint kinase to maintain chromatin integrity. Biochim Biophys Acta 1783, 1595-1604.
- Lopez-Aviles, S., Lambea, E., Moldon, A., Grande, M., Fajardo, A., Rodriguez-Gabriel, M.A., Hidalgo, E., and Aligue, R. (2008). Activation of Srk1 by the mitogen-activated protein kinase Sty1/Spc1 precedes its dissociation from the kinase and signals its degradation. Mol Biol Cell 19, 1670-1679.
- Lopez-Aviles, S., Grande, M., Gonzalez, M., Helgesen, A.L., Alemany, V., Sanchez-Piris, M., Bachs, O., Millar, J.B., and Aligue, R. (2005). Inactivation of the Cdc25 phosphatase by the stress-activated Srk1 kinase in fission yeast. Mol Cell 17, 49-59.