General methods for large biological networks applied to fruit fly models

Abstract

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-calledsegment polarity (SP) genes. It is the asymmetric expression of SPgenes which creates the fruit-fly's segmental structure. The SP genesand their products (e.g. proteins) can be said to form a system which isself-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 ismathematically interesting as it can be thought of in a differentway - multiple symmetries in the same system. This is unusual and weattempt to explain how it is possible using a mathematical modelconstructed by von Dassow et al. When trying to understand abiological system of this kind, there are two main approaches -reductionist and holistic. We try to show that they are notmutually exclusive - we look at the whole system but reduce what ismeant by the whole.For example, von Dassow's model is large scale and, using it as atemplate, we show that a similar (but smaller) model inherits itsproperties. Smaller models can be made by short-handing thetranslation 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 ofkey SP genes (engrailed and wingless) takes places only whencumulative regulation of the wingless gene by two SP proteins isweak. The absence of this regulation would explain coexistence ofmultiple mathematical symmetries in one system (representative ofgenetic asymmetry) as it acts like a division between them. In thisway, the system itself can be thought to divide into two independentsub-systems which can be treated separately.

Date of Award	1 Aug 2012
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Paul Glendinning (Supervisor) & David Broomhead (Supervisor)