David Orrell

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We describe Dizzy, a software tool for stochastically and deterministically modeling the spatially homogeneous kinetics of integrated large-scale genetic, metabolic, and signaling networks. Notable features include a modular simulation framework, reusable modeling elements, complex kinetic rate laws, multi-step reaction processes, steady-state noise(More)
Transcriptional noise is known to be an important cause of cellular heterogeneity and phenotypic variation. The extent to which molecular interaction networks may have evolved to either filter or exploit transcriptional noise is a much debated question. The yeast genetic network regulating galactose metabolism involves two proteins, Gal3p and Gal80p, that(More)
MOTIVATION Genetic regulatory networks are often affected by stochastic noise, due to the low number of molecules taking part in certain reactions. The networks can be simulated using stochastic techniques that model each reaction as a stochastic event. As models become increasingly large and sophisticated, however, the solution time can become excessive;(More)
Computer modelling and simulation are commonly used to analyse engineered systems. Biological systems differ in that they often cannot be accurately characterised, so simulations are far from exact. Nonetheless, we argue in this paper that evolution results in recurring, dynamic organisational principles in biological systems, and that simulation can help(More)
Bifurcation diagrams which allow one to visualise changes in the behaviour of low dimensional nonlinear maps as a parameter is altered are common. Visualisation in higher dimensional systems is more difficult. A straightforward method to visualise bifurcations in flows of high dimensional nonlinear dynamical systems is presented, using the Lorenz ’96(More)
The average number of mRNA molecules per active gene in yeast can be remarkably low. Consequently, the relative number of copies of each transcript per cell can vary greatly from moment to moment. When these transcripts are encoding metabolic enzymes, how do the resulting variations in enzyme concentrations affect the regulation of metabolic intermediates?(More)
EDITORIAL SYNOPSIS Endocrine and exocrine pancreatic function was studied in a small group of controlled patients and in patients with chronic pancreatitis and with mild diabetes mellitus. Patients with chronic pancreatitis showed impaired production of pancreatic enzyme and inadequate production of insulin but no close correlation between exocrine and(More)
Positive and negative feedback loops, for example, where a protein regulates its own transcription, play an important role in many genetic regulatory networks. Such systems will be subject to internal noise, which occurs due to the small number of molecules taking part in some reactions. This paper examines the effect of feedback loops on noise levels.(More)
In the past five years, there has been significant progress in developing high-speed algorithms for solving the stochastic kinetics of complex biochemical networks. In this section, we briefly survey some of these algorithms. Gillespie proposed a discrete-event Monte Carlo technique for generating approximate solutions to the chemical master equation for(More)