Team:St Andrews/project/modelling

Hello and welcome to the St. Andrews iGEM 2010 modelling pages. Here we present our work completed throughout the 2010/2011 summer, the methodology behind our various models, and some of the conclusions we drew from those pieces of work.

We have written systems of differential equations to mathematically describe biological functions. Our models are written in C++, and the differential equations have been solved using the forth order Runge-Kutta method. Originally, we were using R – a programme for statistical computing and graphics – however the lack of flexibility offered by this, and specifically biological modelling packages, led us to use C++, a compiled (and therefore faster) general purpose programming language.

Our project can be divided into two main components: the engineering of a bistable switch into the LuxR quorum sensing system, and the integration of CqsA (the biosynthetic enzyme present in the cholera system) into the LuxR circuit. The aim of the modeling side of the project was to treat these two tasks independently and on their completion construct a combined model. However, this initial aim was proved to be almost impossible due to the lack of rate constants for the cholera system, which has only been understood in its full complexity relatively recently [1]. In order to reach a compromise, we have built a number of qualitatively accurate models for the bistable LuxR system, and outlined a framework of differential equations for the cholera system which are correct at the time of writing, and which requires more rate constants to be of further use. The work done on the bistable switch included an investigation into why exactly such a configuration of genes exhibits hysteretic behavior, and what parameters are of importance in determining the “level” of bistability of the system.

To be determined...