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

Abstract

SummaryApoptotic 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.

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

“…We are interested in regulating the growth of tumor cells, and in our virtual laboratory, we already have ~325 reactions, including EGF/MAPK/JAK-STAT, 20 PI3K, 29 and caspases 30–32 pathways. We integrate the canonical Wnt pathway and other pathways, such as Notch, 33 Hh, 34 and hypoxia stress pathways (Fig.…”

“…Although a large amount of information on this pathway has been reported in the literature so far, part of this information is already stored in our platform, because this pathway has cross talk with pathways that we have modeled earlier, such as Epidermal growth factor (EGF)/Mitogen-activated protein kinase (MAPK)/Janus kinase-Signal transducer and activator of transcription protein pathway (JAK-STAT), 28 PI3K, 29 and caspases. [30][31][32] We have integrated into the model the canonical and noncanonical pathways as well as Notch, 33 Hedgehog, 34 Figure 1. Wnt/β-catenin canonical pathway.…”

“…signaling pathways required and previously simulated. We are interested in regulating the growth of tumor cells, and in our virtual laboratory, we already have ∼325 reactions, including EGF/MAPK/JAK-STAT, 20 PI3K, 29 and caspases [30][31][32] pathways. We integrate the canonical Wnt pathway notes: Example of reactions used for the model.…”

Integration of Pro-Apoptosis and Pro-Survival Signalling Pathways: A Useful Approach to In silico Biomedical Research

“…The main characteristics of our BTSSOC-based framework for simulating intracellular signalling pathways are reported in Table 1. A detailed explanation of this framework can be found at [7][8][9][10][11].…”

“…However, considerable crosstalk exists between the intrinsic and extrinsic pathway including PI3K, PKC and MAPK [5,6]. In previous works we have used successfully a computational framework based on the notion of tuple spaces for modelling and simulation the signalling pathway mentioned above [7][8][9][10][11]. In this paper, using the tuple spacebased framework, we integrate all these pathways in order to dissect each one considering the points of crosstalk, this allows us to highlight the regulatory proteins already described, and to "eliminate" proteins which are difficult to remove in vivo or in vitro.…”