Robustness of Bistable Switches in Gene Regulatory Networks
Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
Gene expression often reacts to intra- and extra-cellular signals in an ”on-off” switchlike manner. These switches, which display hysteresis, correspond to multiple steady-state solutions of the gene regulatory network and are created through saddle-node bifurcations at which a single real eigenvalue of the local Jacobian crosses the imaginary axis for changes in some system parameter. From control theory, it is well known that such an instability can be induced by a single positive feedback loop, possibly involving only a single gene and its corresponding mRNA. However, experimental results have suggested that bistable switches often involve several interlinked feedback loops. Since such a design is relatively costly, it is reasonable to assume that the excessive loops serve a purpose. A standing hypothesis is that the existence of multiple loops improves both the performance and the robustness of the switches. With performance is here understood the speed of switching, while robustness usually refers to the sensitivity of the switch with respect to noisy signals. The aim of this project is to consider these claims, and in particular the one concerning robustness, from a control theoretic perspective. First, an analysis of some specific biological examples will be performed, considering robustness both with respect to noise and with respect to model (systems) perturbations. In the second part, the aim is to propose a multiple loop design that provides optimal robustness.
Place, publisher, year, edition, pages
2007. , 67 p.
IdentifiersURN: urn:nbn:se:kth:diva-106248OAI: oai:DiVA.org:kth-106248DiVA: diva2:573475
Subject / course
Master of Science in Engineering
Jacobsen, Elling W