Control Theoretic Perspectives on Analysis and Synthesis in Systems and Synthetic Biology

Prof. Vishwesh V. Kulkarni
Visiting Professor at the Department of Electrical Engineering, University of Minnesota, Minneapolis

Abstract: Advances in microarray and assay technologies are facilitating increasingly large amounts of laboratory data for the analysis of a variety of in vivo biological networks such as gene regulatory networks, gene-protein interaction networks, and metabolite networks. At the same time, advances in DNA strand displacement techniques are facilitating means to develop in vitro controllers that could be coupled to control these in vivo networks.  In this talk, we present results on (1) estimation of complex in vivo networks and (2) synthesis of some simple in vitro networks. Specifically, we present a theory to derive piecewise affine ordinary differential equation models of stable in vivo networks using steady-state data. These models can also capture constant as well as time-varying time delays. Such delays are encountered in practice due to, for example, lags associated with the transcription and translation processes. A use of these results is illustrated through case studies on networks affected by malaria and glioblastoma. To synthesize the required in vitro controllers, we show how L1 and dynamic inversion theory can be used to synthesize robust tunable networks of transcriptional oscillators. As an example, extensions of the Elowitz-Leibler oscillator and the Kim-Winfree oscillators are presented, and the use of DNA strand displacement techniques to synthesize simple controllers such as proportional (P) controller, and proportional+integrator (PI) controller is illustrated.  The talk is concluded by stating the relevance of these results to biomolecular computing.

Biosketch: Prof. Vishwesh V. Kulkarni is a Visiting Professor at the Department of Electrical Engineering, University of Minnesota, Minneapolis, courtesy Prof. Marc Riedel.  His research interests include systems and synthetic biology, nonlinear control theory, and resource allocation in distributed systems. He received PhD in Electrical Engineering from the University of Southern California, Los Angeles, in May 2001. He was a postdoctoral researcher at the Laboratory for Information and Decision Sciences, Massachusetts Institute of Technology, 2001-03 and at the Department of Electrical Engineering, University of Colorado, Boulder, 2004-05. In 2005, he co-founded a technology licensing company named Sentina Systems, Inc. in Boston, MA, and helped the early stage technology transfer to Sedemac, which is now a 30 employee company in Mumbai, India.  He was an Assistant Professor at the Department of Electrical Engineering, Indian Institute of Technology Bombay, Mumbai, India, 2006-2010. He is co-authoring a research monograph on a nonlinear stability analysis of certain biological networks. He is co-editing a book on systems and synthetic biology; the publisher is Springer Verlag.