Systems biology beyond networks: Generating order from disorder through self-organization

Abstract

Erwin Schrödinger pointed out in his 1944 book “What is Life” that one defining attribute of biological systems seems to be their tendency to generate order from disorder defying the second law of thermodynamics. Almost parallel to his findings, the science of complex systems was founded based on observations on physical and chemical systems showing that inanimate matter can exhibit complex structures although their interacting parts follow simple rules. This is explained by a process known as self-organization and it is now widely accepted that multi-cellular biological organisms are themselves self-organizing complex systems in which the relations among their parts are dynamic, contextual and interdependent. In order to fully understand such systems, we are required to computationally and mathematically model their interactions as promulgated in systems biology. The preponderance of network models in the practice of systems biology inspired by a reductionist, bottom-up view, seems to neglect, however, the importance of bidirectional interactions across spatial scales and domains. This approach introduces a shortcoming that may hinder research on emergent phenomena such as those of tissue morphogenesis and related diseases, such as cancer. Another hindrance of current modeling attempts is that those systems operate in a parameter space that seems far removed from biological reality. This misperception calls for more tightly coupled mathematical and computational models to biological experiments by creating and designing biological model systems that are accessible to a wide range of experimental manipulations. In this way, a comprehensive understanding of fundamental processes in normal development or of aberrations, like cancer, will be generated.

An automated training paradigm reveals long-term memory in planaria and its persistence through head regeneration

“…However, such results are now made more plausible by modern discoveries such as epigenetic modification, which occurs in many cell types, not just the CNS (Arshavsky, 2006;Day and Sweatt, 2010;Ginsburg and Jablonka, 2009;Levenson and Sweatt, 2005;Zovkic et al, 2013) and RNAi (Smalheiser et al, 2001). It is likely that brain remodeling (plasticity during learning) and regeneration are both regulated via epigenetic pathways that determine patterns of self-organization of neural (Arendt, 2005;Davies, 2012;Kennedy and Dehay, 2012;Saetzler et al, 2011) and non-neural but electrically communicating cells (Levin, 2012;Mondia et al, 2011;Oviedo et al, 2010;Tseng and Levin, 2013).…”

Chromatin remodeling system, cancer stem-like attractors, and cellular reprogramming

“…Indeed, the adoption of the information paradigm expressed by the central dogma, which is linear, deprived the organism of its physicality resulting in the marginalization of the role of mechanics and electromagnetic forces in morphogenesis [77]. The essays by Saetzler et al [78] and by Bizzarri et al [79] focus on the role of mechanics in development and cancer while the others address electromagnetic interactions in cell communication. Saetzler et al [75] argue for the adoption of the organicist approach, whereby both a bottom-up and top-down causality are taken into consideration when explaining biological phenomena at large, and carcinogenesis in particular.…”

Le cancer et ses gènes insaisissables

“…La perspective que nous proposons modifie les priorités de recherche dans le domaine du cancer, et plus largement en biologie [25]. Premièrement, la renaissance de la biologie des systèmes, discipline dont les racines se trouvent dans l'école viennoise de von Bertalanffy et de Weiss [26], où l'organicisme et les causalités à la fois ascendantes et descendantes sont tous pris en compte, ouvre la possibilité de comprendre des phénomènes complexes [27,28]. Deuxièmement, les nouvelles disciplines d'ingénierie de tissus et la recherche sur les biomatériaux, originalement prévues pour produire des tissus à des fins de transplantation, ont fait renaître l'intérêt de la biophysique pour les études de morphogenèse dans le développement et dans le cancer [29].…”