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Title: General methods for large biological networks applied to fruit fly models
Author: Irving, Andrew David
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2012
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A key part of a fruit fly's development is the formation of segmentsin its body. These structures are built by the protein forms of so-called segment polarity (SP) genes. It is the asymmetric expression of SP genes which creates the fruit-fly's segmental structure. The SP genes and their products (e.g. proteins) can be said to form a system which is self-regulating, i.e. genes are used to make proteins and, in turn, proteins are used to turn genes on or off. How this system achieves stable asymmetry of this kind is mathematically interesting as it can be thought of in a different way - multiple symmetries in the same system. This is unusual and we attempt to explain how it is possible using a mathematical model constructed by von Dassow et al. When trying to understand a biological system of this kind, there are two main approaches - reductionist and holistic. We try to show that they are not mutually exclusive - we look at the whole system but reduce what is meant by the whole. For example, von Dassow's model is large scale and, using it as a template, we show that a similar (but smaller) model inherits its properties. Smaller models can be made by short-handing the translation process (through which RNA is used to make protein) wherever an SP gene has a unique protein form. Our data indicates that the simultaneous wild-type expression of key SP genes (engrailed and wingless) takes place only when cumulative regulation of the wingless gene by two SP proteins is weak. The absence of this regulation would explain coexistence of multiple mathematical symmetries in one system (representative of genetic asymmetry) as it acts like a division between them. In this way, the system itself can be thought to divide into two independent sub-systems which can be treated separately.
Supervisor: Glendinning, Paul; Broomhead, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: systems ; biology ; drosophila ; segment ; polarity ; network