A Multiscale Modeling Framework Based on P Systems

Cellular systems present a highly complex organization at different scales including the molecular, cellular and colony levels. The complexity at each one of these levels is tightly interrelated. Integrative systems biology aims to obtain a deeper understanding of cellular systems by focusing on the systemic and systematic integration of the different levels of organization in cellular systems. The different approaches in cellular modeling within systems biology have been classified into mathematical and computational frameworks. Specifically, the methodology to develop computational models has been recently called executable biology since it produces executable algorithms whose computations resemble the evolution of cellular systems. In this work we present P systems as a multiscale modeling framework within executable biology. P system models explicitly specify the molecular, cellular and colony levels in cellular systems in a relevant and understandable manner. Molecular species and their structure are represented by objects or strings, compartmentalization is described using membrane structures and finally cellular colonies and tissues are modeled as a collection of interacting individual P systems. The interactions between the components of cellular systems are described using rewriting rules. These rules can in turn be grouped together into modules to characterize specific cellular processes. One of our current research lines focuses on the design of cell systems biology models exhibiting a prefixed behavior through the automatic assembly of these cellular modules. Our approach is equally applicable to synthetic as well as systems biology.Kingdom's Engineering and Physical Sciences Research Council EP/ E017215/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/F01855X/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/D019613/

A Multiscale Modeling Framework Based on P Systems

Cellular systems present a highly complex organization at different scales including the molecular, cellular and colony levels. The complexity at each one of these levels is tightly interrelated. Integrative systems biology aims to obtain a deeper understanding of cellular systems by focusing on the systemic and systematic integration of the different levels of organization in cellular systems. The different approaches in cellular modeling within systems biology have been classified into mathematical and computational frameworks. Specifically, the methodology to develop computational models has been recently called executable biology since it produces executable algorithms whose computations resemble the evolution of cellular systems. In this work we present P systems as a multiscale modeling framework within executable biology. P system models explicitly specify the molecular, cellular and colony levels in cellular systems in a relevant and understandable manner. Molecular species and their structure are represented by objects or strings, compartmentalization is described using membrane structures and finally cellular colonies and tissues are modeled as a collection of interacting individual P systems. The interactions between the components of cellular systems are described using rewriting rules. These rules can in turn be grouped together into modules to characterize specific cellular processes. One of our current research lines focuses on the design of cell systems biology models exhibiting a prefixed behavior through the automatic assembly of these cellular modules. Our approach is equally applicable to synthetic as well as systems biology.Kingdom's Engineering and Physical Sciences Research Council EP/ E017215/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/F01855X/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/D019613/

Design and Analysis of Genetically Constructed Logic Gates

Synthetic biology, comprising many aspects including in vivo, in vitro and in silico techniques, models and methods, programming paradigms and tools, is a rapidly growing field with promising potential in building new synthetically constructed devices and systems. Synthetic biology features unconventional biological systems that do not naturally exist in nature. In this paper, we discuss a software platform, Infobiotics Workbench, developed to perform in silico experiments for synthetic biology systems. We utilise the tool on an unconventional system, a genetic logic gate

A property-driven methodology for formal analysis of synthetic biology systems

yesThis paper proposes a formal methodology to analyse bio-systems, in particular synthetic biology systems. An integrative analysis perspective combining different model checking approaches based on different property categories is provided. The methodology is applied to the synthetic pulse generator system and several verification experiments are carried out to demonstrate the use of our approach to formally analyse various aspects of synthetic biology systems.EPSR

A general framework for modeling growth and division of mammalian cells

BACKGROUND: Modeling the cell-division cycle has been practiced for many years. As time has progressed, this work has gone from understanding the basic principles to addressing distinct biological problems, e.g., the nature of the restriction point, how checkpoints operate, the nonlinear dynamics of the cell cycle, the effect of localization, etc. Most models consist of coupled ordinary differential equations developed by the researchers, restricted to deal with the interactions of a limited number of molecules. In the future, cell-cycle modeling--and indeed all modeling of complex biologic processes--will increase in scope and detail. RESULTS: A framework for modeling complex cell-biologic processes is proposed here. The framework is based on two constructs: one describing the entire lifecycle of a molecule and the second describing the basic cellular machinery. Use of these constructs allows complex models to be built in a straightforward manner that fosters rigor and completeness. To demonstrate the framework, an example model of the mammalian cell cycle is presented that consists of several hundred differential equations of simple mass action kinetics. The model calculates energy usage, amino acid and nucleotide usage, membrane transport, RNA synthesis and destruction, and protein synthesis and destruction for 33 proteins to give an in-depth look at the cell cycle. CONCLUSIONS: The framework presented here addresses how to develop increasingly descriptive models of complex cell-biologic processes. The example model of cellular growth and division constructed with the framework demonstrates that large structured models can be created with the framework, and these models can generate non-trivial descriptions of cellular processes. Predictions from the example model include those at both the molecular level--e.g., Wee1 spontaneously reactivates--and at the system level--e.g., pathways for timing-critical processes must shut down redundant pathways. A future effort is to automatically estimate parameter values that are insensitive to changes