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Cell Growth and Size Homeostasis in Proliferating Mammalian Cells (CellCycleGrowthSize)
Date du début: 1 août 2011, Date de fin: 31 juil. 2015 PROJET  TERMINÉ 

Cell size is central to cell function and ultimately to tissue architecture. Size reflects a balance between cell growth - steadily increase of size, and cytokinesis which halves the cell’s size on each division. How cells attain and maintain their size is a fundamental question that has fascinated generations of biologists, but the answer remains obscure. For proliferating cells growing in unvarying conditions, cell size is basically time-invariant, suggesting that the growth cycle and the cell cycle are coupled. In yeast, an intrinsic size-sensing mechanism coordinates cell cycle with cell growth. Whether such a mechanism is restricted to single-celled organisms is a long-lasting debate. These problems pioneered by Mitchison, Nurse and Zetterberg, captivated the scientific community in the past. But the real challenge of monitoring growth of objects as minute as cells, left these questions neglected for decades.In order to meet the challenge, I have combined cell biology approaches with engineering and mathematics, and was able to overcome long-standing experimental limitations, and, for the first time, to accurately describe the growth (size over time) of a proliferating mammalian cell. These studies suggested that at least some mammalian cells must have an intrinsic size control mechanism that, like in yeast, coordinates cell size with cell division. My work, performed in Marc Kirschner lab at Harvard, was published as a full article in Science.Here I propose to study the physiology and the molecular basis of size homeostasis in proliferating mammalian cells. Using advanced methodologies to monitor cell growth, cell cycle and cell size, and by applying cell and systems biology approaches to cell growth and cell cycle regulation, I aim to elucidate i) whether size-sensing mechanism typically exist in animal cells and ii) the underlying mechanism linking cell growth to cell cycle in mammalian systems with relevance to cancer, differentiation and regeneration

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