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  5. Coordination between cell size and global gene expression
 
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Coordination between cell size and global gene expression
File(s)
Martinez-Segura-A-2018-PhD-Thesis.pdf (3.51 MB)
Thesis
Author(s)
Martínez Segura, Amalia
Type
Thesis
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.
Version
Open Access
Date Issued
2017-09
Date Awarded
2018-01
URI
http://hdl.handle.net/10044/1/62906
DOI
https://doi.org/10.25560/62906
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
License URL
Attribution-NonCommercial-NoDerivatives 4.0 International
Advisor
Marguerat, Samuel
Sponsor
Medical Research Council (Great Britain)
Grant Number
1371272
Publisher Department
Institute of Clinical Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)
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