Intercellular Coupling Regulates the Period of the Segmentation Clock

Herrgen, Leah; Ares, Saúl; Morelli, Luis G.; Schröter, Christian; Jülicher, Frank; Oates, Andrew C.

doi:10.1016/j.cub.2010.06.034

Cited by 161 publications

(268 citation statements)

References 55 publications

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“…synchronization mechanism, e.g., changes to the timing of Delta-Notch signaling, where the mathematical model is able to capture the effects of such an experimental perturbation (RiedelKruse et al, 2007). The phase oscillator model of Herrgen et al (2010) predicted how the segmentation clock period would change in a novel zebrafish mutant, a prediction that was borne out upon the creation of the mutant. Such borne out prediction about experimental interventions internal to the system increase the plausibility that the models capture actual causal structure (Section 3.2).…”

Section: Synchronized Oscillations: the Vertebrate Segmentation Clockmentioning

confidence: 99%

Systems biology and the integration of mechanistic explanation and mathematical explanation

Brigandt

2013

Studies in History and Philosophy of Science Part C: Studies in

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The paper discusses how systems biology is working toward complex accounts that integrate explanation in terms of mechanisms and explanation by mathematical models-which some philosophers have viewed as rival models of explanation. Systems biology is an integrative approach, and it strongly relies on mathematical modeling. Philosophical accounts of mechanisms capture integrative in the sense of multilevel and multifield explanations, yet accounts of mechanistic explanation (as the analysis of a whole in terms of its structural parts and their qualitative interactions) have failed to address how a mathematical model could contribute to such explanations. I discuss how mathematical equations can be explanatorily relevant. Several cases from systems biology are discussed to illustrate the interplay between mechanistic research and mathematical modeling, and I point to questions about qualitative phenomena (rather than the explanation of quantitative details), where quantitative models are still indispensable to the explanation. Systems biology shows that a broader philosophical conception of mechanisms is needed, which takes into account functional-dynamical aspects, interaction in complex networks with feedback loops, system-wide functional properties such as distributed functionality and robustness, and a mechanism's ability to respond to perturbations (beyond its actual operation). I offer general conclusions for philosophical accounts of explanation.

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Section: Synchronized Oscillations: the Vertebrate Segmentation Clockmentioning

confidence: 99%

Systems biology and the integration of mechanistic explanation and mathematical explanation

Brigandt

2013

Studies in History and Philosophy of Science Part C: Studies in

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“…Such mathematical modeling can accompany experimental studies of manipulated synchrony behavior, by means of changes to the timing of Delta-Notch signaling across cells (Riedel-Kruse et al 2007). Using a phase oscillator model approach, Herrgen et al (2010) theoretically predicted how the segmentation clock period would change in a novel zebrafish mutant. Their prediction was borne out upon creation of the mutant.…”

Section: Mathematical Models Of the Origin Of Morphological Structuresmentioning

confidence: 99%

“…Since the model is meant to capture the effects of interventions on molecular components internal to the biological system modeled, the model is meant to get at causal features, so that the 'predictive model' is explanatory (assuming that it is fully realistic). In some cases a model-derived prediction about a novel modification to the organismal system motivates the experimental creation of a new mutant, so as to test the prediction about the intervention in turn (Herrgen et al 2010;Manu et al 2009b).…”

Section: Explanatory Relevance and How Mathematical Models Can Mechanmentioning

confidence: 99%

Evolutionary Developmental Biology and the Limits of Philosophical Accounts of Mechanistic Explanation

Brigandt

2015

History, Philosophy and Theory of the Life Sciences

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Evolutionary developmental biology (evo-devo) is considered a 'mechanistic science,' in that it causally explains morphological evolution in terms of changes in developmental mechanisms. Evo-devo is also an interdisciplinary and integrative approach, as its explanations use contributions from many fields and pertain to different levels of organismal organization. Philosophical accounts of mechanistic explanation are currently highly prominent, and have been particularly able to capture the integrative nature of multifield and multilevel explanations. However, I argue that evo-devo demonstrates the need for a broadened philosophical conception of mechanisms and mechanistic explanation.Mechanistic explanation (in terms of the qualitative interactions of the structural parts of a whole) has been developed as an alternative to the traditional idea of explanation as derivation from laws or quantitative principles. Against the picture promoted by Carl Craver, that mathematical models describe but usually do not explain, my discussion of cases from the strand of evo-devo which is concerned with developmental processes points to qualitative phenomena where quantitative mathematical models are an indispensable part of the explanation. While philosophical accounts have focused on the actual organization and operation of mechanisms, properties of developmental mechanisms that are about how a mechanism reacts to modifications are of major evolutionary significance, including robustness, phenotypic plasticity, and modularity. A philosophical conception of mechanisms is needed that takes into account quantitative changes, transient entities and the generation of novel types of entities, feedback loops and complex interaction networks, emergent properties, and, in particular, functional-dynamical aspects of mechanisms, including functional (as opposed to structural) organization and distributed, system-wide phenomena. I conclude with general remarks on philosophical accounts of explanation.

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“…These predictions have been confirmed experimentally and have led to the discovery of the first mutants with altered collective period, so called period mutants. 2 This example shows how the analysis of effective theoretical descriptions can motivate the design of experimental perturbations, and lead to the discovery of interesting biological phenomena. output of these interactions regulates many cellular functions.…”

Section: Introductionmentioning

confidence: 99%

Noise and Oscillations in Biological Systems: Multidisciplinary Approach Between Experimental Biology, Theoretical Modelling and Synthetic Biology

Ullner¹,

Ares

Morelli

et al. 2012

Int. J. Mod. Phys. B

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Rapid progress of experimental biology has provided a huge flow of quantitative data, which can be analyzed and understood only through the application of advanced techniques recently developed in theoretical sciences. On the other hand, synthetic biology enabled us to engineer biological models with reduced complexity. In this review we discuss that a multidisciplinary approach between this sciences can lead to deeper understanding of the underlying mechanisms behind complex processes in biology. Following the mini symposia "Noise and oscillations in biological systems" on Physcon 2011 we have collected different research examples from theoretical modeling, experimental and synthetic biology.

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Intercellular Coupling Regulates the Period of the Segmentation Clock

Cited by 161 publications

References 55 publications

Systems biology and the integration of mechanistic explanation and mathematical explanation

Systems biology and the integration of mechanistic explanation and mathematical explanation

Evolutionary Developmental Biology and the Limits of Philosophical Accounts of Mechanistic Explanation

Noise and Oscillations in Biological Systems: Multidisciplinary Approach Between Experimental Biology, Theoretical Modelling and Synthetic Biology

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