Quorum-sensing synchronization of synthetic toggle switches: A design based on monotone dynamical systems theory

BioRxiv : the Preprint Server for Biology
Evgeni V Nikolaev, Eduardo D Sontag

Abstract

Synthetic constructs in biotechnology, biocomputing, and modern gene therapy interventions are often based on plasmids or transfected circuits which implement some form of "on-off" switch. For example, the expression of a protein used for therapeutic purposes might be triggered by the recognition of a specific combination of inducers (e.g., antigens), and memory of this event should be maintained across a cell population until a specific stimulus commands a coordinated shut-off. The robustness of such a design is hampered by molecular ("intrinsic") or environmental ("extrinsic") noise, which may lead to spontaneous changes of state in a subset of the population and is reflected in the bimodality of protein expression, as measured for example using flow cytometry. In this context, a "majority-vote" correction circuit, which brings deviant cells back into the desired state, is highly desirable, and quorum-sensing has been suggested as a way for cells to broadcast their states to the population as a whole so as to facilitate consensus. In this paper, we propose what we believe is the first such design that has mathematically guaranteed properties of stability and auto-correction. Our approach is guided by concepts and theory from ...Continue Reading

Related Concepts

Flow Cytometry
Genes
Environment
Anatomic Bifurcation
DNA Stability Analysis
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