Oscillatory stimuli differentiate adapting circuit topologies
Autor: | Nahal Mansouri, Sahand Jamal Rahi, Frederick R. Cross, Alexander Y. Katsov, Johannes Larsch, Eduardo D. Sontag, Kresti Pecani, Krasimira Tsaneva-Atanasova |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Bistability Saccharomyces cerevisiae Network topology Topology Biochemistry Models Biological Article 03 medical and health sciences 0302 clinical medicine Robustness (computer science) Negative feedback Animals Differential (infinitesimal) Caenorhabditis elegans Molecular Biology Positive feedback Feedback Physiological Neurons Basis (linear algebra) Cell Cycle Adaptation Physiological/physiology Cell Cycle/physiology Feedback Physiological/physiology Gene Expression Regulation/physiology Neurons/physiology Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae/metabolism Cell Biology Wiring diagram Adaptation Physiological 030104 developmental biology Gene Expression Regulation 030217 neurology & neurosurgery Biotechnology |
Zdroj: | Nature methods, vol. 14, no. 10, pp. 1010-1016 Nature methods |
Popis: | Biology emerges from interactions between molecules, which are challenging to elucidate with current techniques. An orthogonal approach is to probe for 'response signatures' that identify specific circuit motifs. For example, bistability, hysteresis, or irreversibility are used to detect positive feedback loops. For adapting systems, such signatures are not known. Only two circuit motifs generate adaptation: negative feedback loops (NFLs) and incoherent feed-forward loops (IFFLs). On the basis of computational testing and mathematical proofs, we propose differential signatures: in response to oscillatory stimulation, NFLs but not IFFLs show refractory-period stabilization (robustness to changes in stimulus duration) or period skipping. Applying this approach to yeast, we identified the circuit dominating cell cycle timing. In Caenorhabditis elegans AWA neurons, which are crucial for chemotaxis, we uncovered a Ca 2+ NFL leading to adaptation that would be difficult to find by other means. These response signatures allow direct access to the outlines of the wiring diagrams of adapting systems. |
Databáze: | OpenAIRE |
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