Computational Systems Biology of Saccharomyces cerevisiae Cell Growth and Division

dc.contributor.advisor

Hartemink, Alexander J

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Haase, Steven B

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Mayhew, Michael Benjamin

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2014-08-27T15:22:06Z

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2015-02-23T05:30:05Z

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2014

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Computational Biology and Bioinformatics

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Cell division and growth are complex processes fundamental to all living organisms. In the budding yeast, Saccharomyces cerevisiae, these two processes are known to be coordinated with one another as a cell's mass must roughly double before division. Moreover, cell-cycle progression is dependent on cell size with smaller cells at birth generally taking more time in the cell cycle. This dependence is a signature of size control. Systems biology is an emerging field that emphasizes connections or dependencies between biological entities and processes over the characteristics of individual entities. Statistical models provide a quantitative framework for describing and analyzing these dependencies. In this dissertation, I take a statistical systems biology approach to study cell division and growth and the dependencies within and between these two processes, drawing on observations from richly informative microscope images and time-lapse movies. I review the current state of knowledge on these processes, highlighting key results and open questions from the biological literature. I then discuss my development of machine learning and statistical approaches to extract cell-cycle information from microscope images and to better characterize the cell-cycle progression of populations of cells. In addition, I analyze single cells to uncover correlation in cell-cycle progression, evaluate potential models of dependence between growth and division, and revisit classical assertions about budding yeast size control. This dissertation presents a unique perspective and approach towards comprehensive characterization of the coordination between growth and division.

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https://hdl.handle.net/10161/9089

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Bioinformatics

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Statistics

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Cellular biology

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Bayesian statistics

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cell cycle

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cell growth

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image analysis

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systems biology

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Computational Systems Biology of Saccharomyces cerevisiae Cell Growth and Division

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Dissertation

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6

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