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| One of the challenges in modelling biochemical networks is their combinatorial complexity that gives rise to large number of molecular species even in relatively simple systems that involve multiple modifications. Rule-based modelling has been proposed as a framework to effectively deal with this problem. Here, I will present two example of applications of rule-based modelling to the study of signalling in cellular systems. The first example is on the study of ultra-sensitivity in multi-site phosphorylation systems. We show that multi-site phosphorylation can produce local saturation of enzymes, providing a mechanism for ultra-sensitivity even if globally enzymes are not saturated. In the second example, we will model oligomerization in FRET-based biosensors and illustrate that the read-out of biosensors can be highly non-linear. We propose optimal design and working regimes for biosensors to produce reliable reporting. |
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