Editorial: Computational modelling of cell & tissue processes & function

Abstract

Computational modelling of whole biological systems from cells to organs is gaining momentum in cell biology and disease studies. This pathway is essential for the derivation of explanatory frameworks that will facilitate the development of a predictive capacity for estimating outcomes or risk associated with particular disease processes and therapeutic or stressful treatments. This article introduces a series of invited papers covering a hierarchy of issues and modelling problems, ranging from crucial conceptual considerations of the validity of cellular modelling through to multi-scale modelling up to organ level. The challenges and approaches in cellular modelling are described, including the potential of 'in silico ' modelling applications for receptor-ligand interactions in cell signalling, simulated organ dysfunction (i.e., heart), human and environmental toxicity and the progress of the IUPS Physiome Project. A major challenge now facing biologists is how to translate the wealth of reductionist detail about cells and tissues into a real understanding of how these systems function and are perturbed in disease processes. In biomedicine, simulation models of biological systems now contain sufficient detail, not only to reconstruct normal functions, but also, to reconstruct major disease states. More widely, simulation modelling will aid the targeting of current 'knowledge gaps' and how to fill them; and also provide a research tool for selecting critical factors from multiple simulated experiments for real experimental design. The envisaged longer-term end- product is the creation of simulation models for predicting drug interactions and harmful side-effects; and their use in therapeutic and environmental health risk management. Finally, we take a speculative look at possible future scenarios in cellular modelling, where it is envisioned that integrative biology will move from being largely qualitative and instead become a highly quantitative, computer-intensive discipline.

Role of mTOR in autophagic and lysosomal reactions to environmental stressors in molluscs

“…Mathematical models provide the conceptual and mathematical formalism to integrate molecular, cellular and whole animal processes (Allen & McVeigh, 2004;Allen & Moore, 2004;Moore & Noble, 2004). Previous studies have shown that network complexity (as evaluated using network connectedness -connectance CV%-and node size) can be used as an indicator of homeostasis or health in cellular systems (Moore, 2010).…”

Is toxicological pathology characterised by a loss of system complexity?

“…This argument can probably also be applied to the ''health" of biological assemblages and ecosystems. Effective diagnosis of chemical pollutant impacts and predictions of their consequences requires that we have a capability to model biological interactions (Moore, 2002;Moore and Noble, 2004;Moore et al, 2006;Noble et al, 1999).…”

Proteome-Based Pathway Modelling of Psychiatric Disorders

“…This ranges from sub-microseconds for molecular-level interactions to days, months, and even years for the development of a disease in humans. The complexities represented are such that descriptive intuition often fails and the combinatorial problems to be addressed become serious challenges [55] .…”