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Coordination between cell size and global gene expression

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Title: Coordination between cell size and global gene expression
Authors: Martínez Segura, Amalia
Item Type: Thesis or dissertation
Abstract: All cells change size during the cell cycle, as they have to double their mass in order to produce two equally sized daughter cells. For biochemical reactions to work as intended in a changing volume, the reactants’ concentration should be stable. Data shows that the total mass of RNA and protein per cell are proportional to cell size. Expression data also shows a coordinated increase of the majority of the transcripts when there is an increase in average cell length \citep{Zhurinsky2010}, the mechanism behind it is still poorly understood. In this study I took advantage of a previously described genetic model in fission yeast to investigate this question. This particular strain has a mutation in the \textit{cdc2} gene that makes the gene product sensitive to a nucleotide analogue. When the drug is added, cells arrest in G2 and start growing in size without replicating their genome or dividing. Using transcriptomics and proteomics, I characterised how all transcripts and the majority of proteins respond to an increase in cell size. As previously described, most transcripts and proteins concentration is proportional to cell size. However, there is a subset of molecules that scape the global regulation that the rest of the genome is subjected to. Examining the features that makes this molecule circumvent the coordination of size and gene expression could reveal what is the mechanism behind it. I also applied a mathematical model to study how the cell allocates its limited resources at a maximal size.
Content Version: Open Access
Issue Date: Sep-2017
Date Awarded: Jan-2018
URI: http://hdl.handle.net/10044/1/62906
DOI: https://doi.org/10.25560/62906
Supervisor: Marguerat, Samuel
Sponsor/Funder: Medical Research Council (Great Britain)
Funder's Grant Number: 1371272
Department: Institute of Clinical Sciences
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Department of Clinical Sciences PhD Theses

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