Multi-scale genetic dynamic modelling II: application to synthetic biology: an algorithmic Markov chain based approach.

We model in detail a simple synthetic genetic clock that was engineered in Atkinson et al. (Cell 113(5):597-607, 2003) using Escherichia coli as a host organism. Based on this engineered clock its theoretical description uses the modelling framework presented in Kirkilionis et al.

Multi-scale genetic dynamic modelling I : an algorithm to compute generators.

We present a new approach or framework to model dynamic regulatory genetic activity. The framework is using a multi-scale analysis based upon generic assumptions on the relative time scales attached to the different transitions of molecular states defining the genetic system. At micro-level such systems are regulated by the interaction of two kinds of molecular players: macro-molecules like DNA or polymerases, and smaller molecules acting as transcription factors.

Exploration of cellular reaction systems.

We discuss and review different ways to map cellular components and their temporal interaction with other such components to different non-spatially explicit mathematical models. The essential choices made in the literature are between discrete and continuous state spaces, between rule and event-based state updates and between deterministic and stochastic series of such updates. The temporal modelling of cellular regulatory networks (dynamic network theory) is compared with static network approaches in two first introductory sections on general network modelling.

Diffusion of a membrane protein, Tat subunit Hcf106, is highly restricted within the chloroplast thylakoid network.

The thylakoid membrane forms stacked thylakoids interconnected by 'stromal' lamellae. Little is known about the mobility of proteins within this system. We studied a stromal lamellae protein, Hcf106, by targeting an Hcf106-GFP fusion protein to the thylakoids and photobleaching.

Bistability and oscillations in chemical reaction networks.

Bifurcation theory is one of the most widely used approaches for analysis of dynamical behaviour of chemical and biochemical reaction networks. Some of the interesting qualitative behaviour that are analyzed are oscillations and bistability (a situation where a system has at least two coexisting stable equilibria). Both phenomena have been identified as central features of many biological and biochemical systems.

Tat-dependent targeting of Rieske iron-sulphur proteins to both the plasma and thylakoid membranes in the cyanobacterium Synechocystis PCC6803.

Cyanobacteria possess a differentiated membrane system and transport proteins into both the periplasm and thylakoid lumen. We have used green fluorescent protein (GFP)-tagged constructs to study the Tat protein transporter and Rieske Tat substrates in Synechocystis PCC6803. The Tat system has been shown to operate in the plasma membrane; we show here that it is also relatively abundant in the thylakoid membrane network, indicating that newly synthesized Tat substrates are targeted to both membrane systems.

Multiscale analysis of reaction networks.

In most natural sciences there is currently the insight that it is necessary to bridge gaps between different processes which can be observed on different scales. This is especially true in the field of chemical reactions where the different abilities to form bonds between different types of atoms and molecules create much of the properties we experience in our everyday life, especially in all biological activity. There are essentially two types of processes related to biochemical reaction networks, the interactions among molecules and interactions involving their conformational changes, so in a sense, their internal state.