An Approach to the Engineering of Cellular Models Based on P Systems

Living cells assembled into colonies or tissues communicate using complex systems. These systems consist in the interaction between many molecular species distributed over many compartments. Among the different cellular processes used by cells to monitor their environment and respond accordingly, gene regulatory networks, rather than individual genes, are responsible for the information processing and orchestration of the appropriate response [16]. In this respect, synthetic biology has emerged recently as a novel discipline aiming at unravelling the design principles in gene regulatory systems by synthetically engineering transcriptional networks which perform a specific and prefixed task [2]. Formal modelling and analysis are key methodologies used in the field to engineer, assess and compare different genetic designs or devices. In order to model cellular systems in colonies or tissues one requires a formalism able to represent the following relevant features: – Single cells should be described as the elementary units in the system. Nevertheless, they cannot be represented as homogeneous points as they exhibit complex structures containing different compartments where specific molecular species interact according to particular reactions. – The molecular interactions taking place in cellular systems are inherently discrete and stochastic processes. This is a key feature of cellular systems that needs to be taken into account when describing their dynamics [9]. – It has been postulated that gene regulatory networks are organised in a modular manner in such a way that cellular processes arise from the orchestrated interactions between different genetic transcriptional units that can be considered separable modules [1]. – Spatial and geometric information must be represented in the system in order to describe processes involving pattern formation. In this work we review recent advances in the use of the computational paradigm membrane computing or P systems as a formal methodology in synthetic biology for the specification and analysis on cellular system models according to the previously presented points

Structure and parameter estimation for cell systems biology models

In this work we present a new methodology for structure and parameter estimation in cell systems biology modelling. Our modelling framework is based on P systems, an unconventional computational paradigm that abstracts from the structure and functioning of the living cell. The process of designing models, consisting of both the optimisation of the modular structure and of the stochastic kinetic parameters, is performed using a memetic algorithm. Specically, we use a nested evolutionary algorithm where the first layer evolves rule structures while the inner layer, implemented also as a genetic algorithm (GA), fine tunes the parameters of the model. Our approach consists of an incremental methodology. Starting from very simple P system modules specifying basic molecular interactions, more complicated modules are produced to model more complex molecular systems. These newly found modules are in turn added to the library of available P systems modules so as to be used subsequently to develop more intricate and circuitous cellular models. The effectiveness of the algorithm was tested on three case studies, namely, molecular complexation, enzymatic reactions and autoregulation in transcriptional networks.Kingdom's Engineering and Physical Sciences Research Council EP/ E017215/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/F01855X/

Understanding osmotic dehydration of tissue structured foods by means of a cellular approach

[EN] This contribution presents a study on osmotic dehydration of tissue structured foods based on a microstructural approach in which simplified systems such as isolated apple cells and protoplasts have been used. An appropriate description of the microstructure of the raw material and its evolution during processing has been evidenced as critical in order to better understand and describe osmotic dehydration processes; as a direct consequence, it is stated that predictive models should incorporate this microstructural information so as to be more reliable. Microstructural changes observed by examining the isolated cells under the microscope along the treatments have been used to identify critical points that separate the stages that a cell undergoes, and which depend also on its particular response to the osmotic treatment (lysis, shrinkage or complete plasmolysis). Irreversible thermodynamics has been used to mathematically describe the process by distinguishing two main stages: one at which significant deformation-relaxation phenomena are coupled with mass transfer, and another one at which the former may be neglected. (C) 2011 Elsevier Ltd. All rights reserved.The authors would like to thank the Ministerio de Educacion y Ciencia (Spain) for financial support, and the organising committee of the International Conference on Food Innovation 2010 (FoodInnova2010) for granting this work with the best oral communication for young scientists award.Seguí Gil, L.; Fito Suñer, PJ.; Fito Maupoey, P. (2012). Understanding osmotic dehydration of tissue structured foods by means of a cellular approach. Journal of Food Engineering. 110(2):240-247. doi:10.1016/j.jfoodeng.2011.05.012S240247110

Investigating biocomplexity through the agent-based paradigm.

Capturing the dynamism that pervades biological systems requires a computational approach that can accommodate both the continuous features of the system environment as well as the flexible and heterogeneous nature of component interactions. This presents a serious challenge for the more traditional mathematical approaches that assume component homogeneity to relate system observables using mathematical equations. While the homogeneity condition does not lead to loss of accuracy while simulating various continua, it fails to offer detailed solutions when applied to systems with dynamically interacting heterogeneous components. As the functionality and architecture of most biological systems is a product of multi-faceted individual interactions at the sub-system level, continuum models rarely offer much beyond qualitative similarity. Agent-based modelling is a class of algorithmic computational approaches that rely on interactions between Turing-complete finite-state machines--or agents--to simulate, from the bottom-up, macroscopic properties of a system. In recognizing the heterogeneity condition, they offer suitable ontologies to the system components being modelled, thereby succeeding where their continuum counterparts tend to struggle. Furthermore, being inherently hierarchical, they are quite amenable to coupling with other computational paradigms. The integration of any agent-based framework with continuum models is arguably the most elegant and precise way of representing biological systems. Although in its nascence, agent-based modelling has been utilized to model biological complexity across a broad range of biological scales (from cells to societies). In this article, we explore the reasons that make agent-based modelling the most precise approach to model biological systems that tend to be non-linear and complex

Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions

Design for Additive Manufacturing: A Method to Explore Unexplored Regions of the Design Space

Additive Manufacturing (AM) technologies enable the fabrication of parts and devices that are geometrically complex, have graded material compositions, and can be customized. To take advantage of these capabilities, it is important to assist designers in exploring unexplored regions of design spaces. We present a Design for Additive Manufacturing (DFAM) method that encompasses conceptual design, process selection, later design stages, and design for manufacturing. The method is based on the process-structure-property-behavior model that is common in the materials design literature. A prototype CAD system is presented that embodies the method. Manufacturable ELements (MELs) are proposed as an intermediate representation for supporting the manufacturing related aspects of the method. Examples of cellular materials are used to illustrate the DFAM method.Mechanical Engineerin

Synthetic biology—putting engineering into biology

Synthetic biology is interpreted as the engineering-driven building of increasingly complex biological entities for novel applications. Encouraged by progress in the design of artificial gene networks, de novo DNA synthesis and protein engineering, we review the case for this emerging discipline. Key aspects of an engineering approach are purpose-orientation, deep insight into the underlying scientific principles, a hierarchy of abstraction including suitable interfaces between and within the levels of the hierarchy, standardization and the separation of design and fabrication. Synthetic biology investigates possibilities to implement these requirements into the process of engineering biological systems. This is illustrated on the DNA level by the implementation of engineering-inspired artificial operations such as toggle switching, oscillating or production of spatial patterns. On the protein level, the functionally self-contained domain structure of a number of proteins suggests possibilities for essentially Lego-like recombination which can be exploited for reprogramming DNA binding domain specificities or signaling pathways. Alternatively, computational design emerges to rationally reprogram enzyme function. Finally, the increasing facility of de novo DNA synthesis—synthetic biology’s system fabrication process—supplies the possibility to implement novel designs for ever more complex systems. Some of these elements have merged to realize the first tangible synthetic biology applications in the area of manufacturing of pharmaceutical compounds.

A universal approach to coverage probability and throughput analysis for cellular networks

This paper proposes a novel tractable approach for accurately analyzing both the coverage probability and the achievable throughput of cellular networks. Specifically, we derive a new procedure referred to as the equivalent uniformdensity plane-entity (EUDPE)method for evaluating the other-cell interference. Furthermore, we demonstrate that our EUDPE method provides a universal and effective means to carry out the lower bound analysis of both the coverage probability and the average throughput for various base-station distribution models that can be found in practice, including the stochastic Poisson point process (PPP) model, a uniformly and randomly distributed model, and a deterministic grid-based model. The lower bounds of coverage probability and average throughput calculated by our proposed method agree with the simulated coverage probability and average throughput results and those obtained by the existing PPP-based analysis, if not better. Moreover, based on our new definition of cell edge boundary, we show that the cellular topology with randomly distributed base stations (BSs) only tends toward the Voronoi tessellation when the path-loss exponent is sufficiently high, which reveals the limitation of this popular network topology