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Title: Spatiotemporal modelling in biology : from transcriptional regulation to plasmid positioning
Author: Ietswaart, Jaldert Hugo Rigobert
ISNI:       0000 0004 5919 5754
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2015
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Here I describe how cycles of mathematical modelling and experimenting have advanced our quantitative understanding of two different processes: transcriptional regulation of the floral repressor FLOWERING LOCUS C (FLC ) in Arabidopsis thaliana and spatial positioning of low copy number plasmids in Escherichia coli. Despite the diversity in biological subjects, my spatiotemporal modelling approach provides a common ground. FLC regulation involves an antisense-mediated chromatin silencing mechanism, where alternative polyadenylation of antisense transcripts is linked to changed histone modifications at the locus and altered expression. Mathematical model predictions of FLC transcriptional dynamics are validated by measurements of total and chromatinbound FLC intronic RNA. This demonstrates that FLC regulation involves a quantitative coordination between transcription initiation and elongation, potentially a general feature of gene regulation in a chromatin context. A quantitative analysis of cellular RNA levels indicates that FLC processing and degradation are well described by Poisson processes. FLC transcription correlates with cell volume, which underlies the large cellular variation in transcript levels. Low copy number plasmids in bacteria require segregation for stable inheritance through cell division. This is often achieved by a parABC locus, comprising an ATPase ParA, DNA-binding protein ParB and a parC region, encoding ParB-binding sites. These components space plasmids equally over the nucleoid, yet the underlying mechanism has not been understood. Here I show mathematically that differences between competing ParA concentrations on either side of a plasmid can specify regular plasmid positioning. This can be achieved regardless of the exact mechanism of plasmid movement. Experimentally, parABC from E. coli plasmid pB171 increases plasmid mobility, inconsistent with models based on plasmid diffusion and immobilization. Instead this observation favours a directed motion model. These results unify previously contradictory models for plasmid segregation and provide a mechanistic basis for selforganized plasmid spacing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available