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Title: Modelling protein localisation and positional information in subcellular systems
Author: Tostevin, Filipe John
ISNI:       0000 0001 3535 5109
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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Cells and their component structures are highly organised. The correct function of many biological systems relies upon not only temporal control of protein levels but also spatial control of protein localisation within cells. Mathematical modelling allows us to quantitatively test potential mechanisms for protein localisation and spatial organisation. Here we present models of three examples of spatial organisation within individual cells. In the bacterium E. coli, the site of cell division is partly determined by the Min proteins. The Min proteins oscillate between the cell poles and suppress formation of the division ring here, thereby restricting division to midcell. We present a stochastic model of the Min protein dynamics, and use this model to investigate partitioning of the Min proteins between the daughter cells during cell division. The Min proteins determine the correct position for cell division by forming a timeaveraged concentration gradient which is minimal at midcell. Concentration gradients are involved in a range of subcellular processes, and are particularly important for obtaining positional information. By analysing the low copy number spatiotemporal uctuations in protein concentrations for a single polar gradient and two oppositelydirected gradients, we estimate the positional precision that can be achieved in vivo. We nd that time-averaging is vital for high precision. The embryo of the nematode C. elegans has become a model system for the study of cell polarity. At the one-cell stage, the PAR proteins form anterior and posterior domains in a dynamic process driven by contraction of cortical actomyosin. We present a continuum model for this system, including a highly simpli ed model of the actomyosin dynamics. Our model suggests that the known PAR protein interactions 5 are insu cient to explain the experimentally observed cytoplasmic polarity. We discuss a number of modi cations to the model which reproduce the correct cytoplasmic distributions.
Supervisor: Howard, Martin Sponsor: EPSRC.
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral