Topology-based Control of Genetic Regulatory Networks
Anil Jayanti Aswani and Claire Tomlin
National Science Foundation CCR-0225610
The traditional control scheme has been to input a signal into a plant, where the signal is derived from either an open loop or a closed loop. This control strategy requires that the plant be able to accept inputs or can be modified to do so. However, this situation is not always true in biological genetic networks; in these systems, there is often no input or obvious modification to allow inputs.
We believe that they require a new paradigm for control. Biotechnology techniques are such that it is easier to make topological changes to a genetic network than it is to either change the states of the pathway or add more elements to the pathway. Thus, for such genetic networks it is important to develop a theory of control based on making large-scale changes (e.g., genetic mutations) to the topology of the network; we provide steps towards such a theory. We highlight some useful results from monotone and hybrid systems theory, and show how these results can be used for such a topological control scheme. We consider the cancer-related p53 pathway as an example; we analyze this system using control theory and devise a controller.
Figure 1: The time course plots for the different pathways display the effect of the abnormality and the controller. Note that p53 is solid, cyclin A is dashed, and MDM2 is dash-dotted.
- A. Aswani and C. Tomlin, “Topology-based Control of Biological Genetic Networks,” Proceedings of 47th IEEE CDC, Cancun, Mexico, December 2008 (to appear).