Cell Cycle and variability
On the list of basic biological processes, the cell cycle ranks must rank in importance just below basic metabolism. As a 'network', to use an atavastic term, the cell cycle presents a realistic mixture of transcriptional and post translational regulation (mostly the later) that does not fall within any existing bioinformatic category. A neglected aspect of cell cycle research over the past two decades, is its variation at the single cell level, which makes contact with earlier work on stochasticity in gene regulation. With Fred Cross, we are making movies as a single yeast cell grows to a colony of ~40 cells, using both phase and fluorescence microscopy. There are many markers available that record defining events in the cell division process. Yeast is a versatile system for 'noise' studies since it can be grown with variable ploidy. Part of this project involves custom image analysis and annotation software.
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•Mode locking the cell cycle Cross FR, Siggia ED. Phys. Rev. E. 72, , (2005).
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•Coherence and timing of cell cycle start examined at single-cell resolution. Bean JM, Siggia ED, Cross FR, Mol Cell 21, 3-14 (2006).
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•The effects of molecular noise and size control on variability in the budding yeast cell cycle. Di Talia S, Skotheim JM, Bean JM, Siggia ED, Cross FR. Nature ;448, 947-51 (2007)
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•A microfluidic device for temporally controlled gene expression and long-term fluorescent imaging in unperturbed dividing yeast cells. Charvin G, Cross FR, Siggia ED. PLoS One. 2008 Jan 23;3(1):e1468
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•Positive feedback of G1 cyclins ensures coherent cell cycle entry. Skotheim JM, Di Talia S, Siggia ED, Cross FR.
Nature. 454:291-6 (2008)
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•Forced periodic expression of G1 cyclins phase-locks the budding yeast cell cycle. Charvin G, Cross FR, Siggia ED.
Proc Natl Acad Sci 106 , 6632-7, (2009)
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•Origin of irreversibility of cell cycle start in budding yeast . Charvin G, Oikonomou C, Siggia ED, Cross FR., PLoS Biol. 2010 Jan 19;8(1):e1000284