Simulation of caspases apoptotic signalling pathway in a tuple space-based bioinformatics infrastructure

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Applying the Tuple Space-Based Approach to the Simulation of the Caspases, an Essential Signalling Pathway

Apoptotic cell death plays a crucial role in development and homeostasis. This process is driven by mitochondrial permeabilization and activation of caspases. In this paper we adopt a tuple spaces-based modelling and simulation approach, and show how it can be applied to the simulation of this intracellular signalling pathway. Specifically, we are working to explore and to understand the complex interaction patterns of the caspases apoptotic and the mitochondrial role. As a first approximation, using the tuple spacesbased in silico approach, we model and simulate both the extrinsic and intrinsic apoptotic signalling pathways and the interactions between them. During apoptosis, mitochondrial proteins, released from mitochondria to cytosol are decisively involved in the process. If the decision is to die, from this point there is normally no return, cancer cells offer resistance to the mitochondrial induction.

Understanding the PI3K/AKT Anti-Apoptotic Signalling Pathway: a Tuple Space-Based Computational Framework for Simulating the Signal Transduction

The PI3K/AKT pathway is one of the main processes involved in cancer development since it primarily controls cellular proliferation and apoptosis. Understanding its behaviour and how it interacts with other pathways or how it is influenced by the presence of specific molecules, is a crucial task in cancer therapy. In this paper we propose a model developed according to the abstractions provided by the Biochemical Tuple Spaces for Self-Organising Coordination framework and simulated on top of TuCSoN. The model and simulation procedure is fully described, demonstrating how much flexible and robust the computational framework is. Simulation results show critical points in the overall cascade, where activations or inhibitions can change the fate of the cell, turning it into apoptosis or proliferation

Understanding the PI3K/AKT Anti-Apoptotic Signalling Pathway: a Tuple Space-Based Computational Framework for Simulating the Signal Transduction

The PI3K/AKT pathway is one of the main processes involved in cancer development since it primarily controls cellular proliferation and apoptosis. Understanding its behaviour and how it interacts with other pathways or how it is influenced by the presence of specific molecules, is a crucial task in cancer therapy. In this paper we propose a model developed according to the abstractions provided by the Biochemical Tuple Spaces for Self-Organising Coordination framework and simulated on top of TuCSoN. The model and simulation procedure is fully described, demonstrating how much flexible and robust the computational framework is. Simulation results show critical points in the overall cascade, where activations or inhibitions can change the fate of the cell, turning it into apoptosis or proliferation

Understanding the PI3K/AKT Anti-Apoptotic Signalling Pathway: a Tuple Space-Based Computational Framework for Simulating the Signal Transduction

The PI3K/AKT pathway is one of the main processes involved in cancer development since it primarily controls cellular proliferation and apoptosis. Understanding its behaviour and how it interacts with other pathways or how it is influenced by the presence of specific molecules, is a crucial task in cancer therapy. In this paper we propose a model developed according to the abstractions provided by the Biochemical Tuple Spaces for Self-Organising Coordination framework and simulated on top of TuCSoN. The model and simulation procedure is fully described, demonstrating how much flexible and robust the computational framework is. Simulation results show critical points in the overall cascade, where activations or inhibitions can change the fate of the cell, turning it into apoptosis or proliferation

Simulation of caspases apoptotic signalling pathway in a tuple space-based bioinformatics infrastructure

Understanding intracellular communication processes is essential, since they allow the cell to perform the totality of its functions. Among them each cell has a self-destruction system that starts and operates in a regulated manner. It is called apoptosis, and includes the decision to start self-destruction as well as the proper execution of the apoptotic program. Caspases, a family of cysteine proteases, are the central regulators of apoptosis. As such, it requires the coordinated activation and execution of multiple sub programmes. Historically, different modelling approaches have been developed to deal with intracellular signalling pathways, from mathematical models – mainly Ordinary Differential Equations (ODEs) – to computational models —process algebra such as stochastic π-calculus (Priami, 1995) and κ-calculus (Danos et al., 2007). Accordingly, different simulation tools have been developed, from mathematical ones – see a survey in (Alves et al., 2006) – to computational ones such as SPiM (Phillips, 2007). While they typically address scenarios with a single compartment, in recent years a trend has emerged which moves from the single global approach to mechanisms and constructs tackling the multi-compartment scenario. In this paper, we adopt a simulation approach based on the notion of Biochemical Tuple Spaces for Self-Organising Coordination (BTS-SOC), introduced in (Viroli and Casadei, 2009), and then show how it can be applied to the simulation of the caspases signalling pathway (MacFarlane and Williams, 2004), which plays a crucial role in the transduction and execution of the apoptotic signal induced by various stimuli

Modeling Intercellular Communication as a Survival Strategy of Cancer Cells: An in Silico Approach on a Flexible Bioinformatics Framework

Intercellular communication is very important for cell development and allows a group of cells to survive as a population. Cancer cells have a similar behavior, presenting the same mechanisms and characteristics of tissue formation. In this article, we model and simulate the formation of different communication channels that allow an interaction between two cells. This is a first step in order to simulate in the future processes that occur in healthy tissue when normal cells surround a cancer cell and to interrupt the communication, thus preventing the spread of malignancy into these cells. The purpose of this study is to propose key molecules, which can be targeted to allow us to break the communication between cancer cells and surrounding normal cells. The simulation is carried out using a flexible bioinformatics platform that we developed, which is itself based on the metaphor chemistry-based model