Improving Robustness and Performance of Engineered Cells via Biomolecular Feedback Design in a Whole-Cell Context

Dr Guy-Bart Stan, Department of Bioengineering of Imperial College London

Abstract

In this talk I will give an overview of some of our research activities in the "Control Engineering Synthetic Biology" group, where we focus our efforts on developing foundational forward-engineering methods to mathematically model, control, and experimentally implement synthetic gene circuits and cellular systems that aim at increasing the robustness, performance, and genetic stability of engineered cells. During the talk, I will propose some approaches to answer the following core questions in synthetic biology design:

• How can we design taking into account shared resources?

• How can we improve the dynamic performance of synbio systems?

• How can we use cells to control their surrounding environment?

In particular, I will present some recent work on the development of various de novo biomolecular feedback mechanisms in bacterial cells (mainly E. coli) that we use to answer the above questions. Our envisioned target applications for these novel designs include cell-based medicine, more efficient biosynthesis, and scale-up in synthetic biology and biotechnology.

Biography

Dr Guy-Bart Stan is a Reader in Engineering Design for Synthetic Biology and the head of the "Control Engineering Synthetic Biology" group at the Department of Bioengineering of Imperial College London, U.K. His group is exploring the mathematical aspects of modelling, analysis and control of biological systems and their applications in synthetic biology (http://www.bg.ic.ac.uk/research/g.stan/group/). In particular, their focus is on the study of core engineering design principles of biological systems with a particular interest in the design and in vivo implementation of biomolecular feedback control mechanisms for the robust and efficient automatic control of natural and synthetic biology systems, including gene regulatory networks and metabolic pathways, with a view to their applications for biotechnology, biosynthesis, advanced cell-based medicine and healthcare.

Dr Stan received is PhD in Applied Sciences (mathematical analysis and control of nonlinear dynamical systems) from the University of Liege (Belgium) in March 2005 and subsequently worked for Philips Applied Technologies as Senior Digital Signal Processing Engineer and Coordinator of the R&D teams at Eindhoven (The Netherlands) and Leuven (Belgium). From January 2006 until December 2009, he worked as PostDoctoral Research Associate in the Control Group of the Department of Engineering at the University of Cambridge, first supported by a EU Marie Curie Intra-European Fellowship (Jan 2006-Dec 2006) and then by the UK EPSRC (Jan 2007 - Dec 2009). He joined Imperial College London in December 2009 as a founding member of the Centre for Synthetic Biology and Innovation (http://www.imperial.ac.uk/synthetic-biology).

He is (co-)author of over 70 peer-reviewed papers and 1 book, and editor of a two volumes book on the use of rigorous systems and control engineering methods for solving important problems in systems biology, synthetic biology and modelling, analysis and control of nonlinear dynamical systems. He is one of the recipients of the prestigious UK EPSRC Fellowship for Growth in Synthetic Biology, that directly supports his research in Synthetic Biology from Feb 2015 until Jan 2020.

Relevant recent papers (all papers are available at http://www.bg.ic.ac.uk/research/g.stan/)
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• Quantifying cellular capacity identifies gene expression designs with reduced burden, F. Ceroni, R. Algar, G.-B. Stan, T. Ellis, Nature Methods, Volume 12 (2015), n°5, doi:10.1038/nmeth.3339.

• Synthetic gene circuits for metabolic control: design trade-offs and constraints, D. Oyarzun, G.-B. Stan*, Journal of the Royal Society Interface, Volume 10 (2013), n°78, doi:10.1098/rsif.2012.0671.

• Noise propagation in synthetic gene circuits for metabolic control, D. Oyarzun, J.-B. Lugagne, G.-B. Stan*, ACS Synthetic Biology (2014), doi:10.1021/sb400126a.

• GeneGuard: a Modular Plasmid System Designed for Biosafety, O. Wright, M. Dalmans, G.-B. Stan, T. Ellis, ACS Synthetic Biology (2014), doi:10.1021/sb500234s.

• SBOL Visual: A Graphical Language for Genetic Designs, J. Y. Quinn, R. S. Cox III, A. Adler, J. Beal, S. Bhatia, Y. Cai, J. Chen, K. Clancy, M. Galdzicki, N. J. Hilson, N. Le Novere, A. J. Maheshwari, J. A. McLaughlin, C. J. Myers, U. P, M. Pocock, C. Rodriguez, L. Soldatova, G.-B. Stan, N. Swainston, A. Wipat, H. M. Sauro, PLoS Biology, 2015, doi:10.1371/journal.pbio.1002310

• Simplified Mechanistic Models of Gene Regulation for Analysis and Design, E. Hancock, G.-B. Stan*, J. Arpino, A. Papachristodoulou, Journal of the Royal Society Interface, Volume 12 (2015), n°108, doi:10.1098/rsif.2015.0312.