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Understanding mammalian gene expression noise as a function of cell growth
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Davies, Philip R. (2020) Understanding mammalian gene expression noise as a function of cell growth. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3491952~S15
Abstract
Mammalian cell growth is a complex process encompassing genome replication, cell mass accumulation and drastic reorganization of the intracellular structure. Each of these processes contributes to gene expression noise, making the design of robust genetic circuits difficult. We use flow cytometry to collect measurements on multiple cell-cycle reporters, which we analyse using probability state modelling. This approach enables us to position each cell into its most likely cell-cycle state. Combining this methodology with measurements of gene expression kinetics such as metabolic labelling of transcription and translation provides a high resolution view into how such activities change during the cell-cycle. Changes in cell-size are another important source of gene expression variation. Cells of different sizes are known to grow at different rates, further confounding our measurements of noise. Using ergodic rate analysis, we correlate our measurements of gene expression kinetics with those of cell-size growth rate as a function of cell-cycle progression. This way, we aim to elucidate the homeostatic mechanisms linking cell growth and gene expression, in order to better understand gene expression noise.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics | ||||
Library of Congress Subject Headings (LCSH): | Gene expression, Cells -- Growth, Genetic regulation | ||||
Official Date: | May 2020 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | School of Life Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Format of File: | |||||
Extent: | 181 leaves : illustrations (some colour) | ||||
Language: | eng |
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