Mitogen activated protein kinase (MAPK) cascade is evolutionally preserved in all eukaryotic cells, and regulates cellular activities as gene expression, mitosis, differentiation, and apoptosis. Recent years have witnessed increase activity in reshaping the MAPK cascade through engineered feedback loops, by referring to heuristic tuning mechanisms to synthesize the feedback. A problem of interest is to determine whether information regarding the underlying biochemical reactions can be used to synthesize robust feedback that will ensure that the resultant circuit has the desired properties. Jointly with Vishwesh Kulkarni from University of Minnesota we consider the problem of engineering feedback in MAPK cascade to synthesize an oscillator of the desired frequency. We show how the L1-control theory can be used for a robust synthesis of the oscillator and we validate the theory in simulations.
- Kulkarni, V., Paranjape, A., Ghusinga, K.R., and Hovakimyan, N., “Synthesis of robust tunable oscillators using mitogen activated protein kinase cascades,” in Systems and Synthetic Biology, 4:331–341, 2010. [pdf]