Biochemical processes, carried out by networks of proteins, mediate the interaction of cells with their environment and are responsible for most of the information processing inside cells. Recently, much interest has been focused on system level studies of such networks, and several approaches have been proposed for their representation and analysis. However, none of the existing approaches fully integrates dynamics, molecular, and biochemical detail.
We propose to model biochemical processes using the pi-calculus, a process algebra originally developed for describing distributed computer processes. In our model, biochemical processes are mathematically well defined, while remaining biologically faithful and transparent. To allow accurate quantitative modeling of biochemical networks, we employ a stochastic variant, the spi-calculus, where actions are assigned rates according to the rates of the corresponding biochemical reactions. Based on this model, we developed a new computer system, called BioPSI, for representation and simulation of biochemical networks.
The modular nature of the calculus allows incremental modeling of complex networks and alternation between different levels of complexity. This is instrumental for studying the modular design of biological systems. We have used the BioPSI system to study a recently proposed model of the circadian clock. Using the ability of the calculus to capture modular structures, we investigated the circadian machinery at two levels of abstraction. First, we modeled the molecular interactions explicitly. Second, we identified a functional module in the system - a hysteresis module - and described the system using this functional module. By using two BioPSI programs, we show that both levels of description are equally good at capturing the behavior of the system, and establish the function of the hysteresis module within the clock and in a wider cellular context.
We are currently extending our modular framework to represent various aspects of molecular localization and compartmentalization, including the movement of molecules between compartments and dynamic rearrangement of cellular compartments. We intend to incorporate the adapted calculus as part of the BioPSI system, to provide a fuller modular framework for molecular interaction, localization and compartmentalization.
