Diego A. Oyarzún

Research Fellow

Hamilton Institute
National University of Ireland, Maynooth
Ireland

email diego.oyarzun [at] nuim [dot] ie

SB 		d.o

Bio

Originally from Valdivia, southern Chile, I graduated in 2006 as Civil Electronic Engineer with a MSc in Electronic Engineering from Universidad Técnica Federico Santa María in Valparaíso, Chile, under the supervision of Prof Mario Salgado. I completed my PhD in the Systems Biology group at the Hamilton Institute under the supervision of Prof Peter Wellstead and Dr Dimitrios Kalamatianos.
Now I'm a Marie Curie Fellow under the Career Enhancement and Mobility Programme of NBIP Ireland. During Feb-Jul 2010 I was a also visiting member of the COMORE team, INRIA Sophia Antipolis, France.

I'm moving: starting January 2011 I will be at the Centre for Synthetic Biology and Innovation in the Dept. of Bioengineering, Imperial College London.

Research interests

  • Dynamics of metabolic & genetic networks
  • Applications of Systems & Control theory to biochemical networks
  • Optimal control
  • Multivariable control system design
  • General Systems Biology & Mathematical Biology

Research in Systems & Mathematical Biology

Interplay between the dynamics of genetic and metabolic networks

cell Upon changes in intra- or extra-cellular conditions, the modulation of metabolic activity allows for resource allocation (activation or suppression of specific pathways) and responses to environmental stimuli. One of the mechanisms that underpins this regulation is feedback genetic control; the dynamics of combined genetic/metabolic systems are well-understood in notable cases such as the Lac operon, but more complex regulatory topologies remain elusive. In this project we aim at characterizing the dynamics of a metabolic network coupled with a genetic circuit via metabolites that regulate enzyme synthesis. The metabolic subsystem is described by a nonlinear control-affine system, whereas the genetic circuit is modeled as a piecewise linear system, which accounts for the typical switch-like behavior of genetic interactions. See conference paper [12] below.

Collaborators: Dr Madalena Chaves (COMORE team, INRIA Sophia Antipolis, France).

Dynamic optimization of metabolic networks

cell It is widely accepted that many biochemical systems have evolved so as to optimize cellular adaptation to environmental conditions. Under this premise we have addressed different optimal control problems aimed at reverse-engineering metabolic networks. We have considered the dynamic optimization of enzyme synthesis rates and/or concentrations for a nonlinear control-affine metabolic network under linear and quadratic cost functions; see my Ph.D. Thesis, journal papers [6-7], and conference papers [4,7].

Collaborators: Prof Brian Ingalls (U. Waterloo, Canada), Prof Rick Middleton (Hamilton Institute), Dr Dimitris Kalamatianos (Hamilton Institute).

Inhibition of cellular receptor systems

This project stemmed from the Ph.D. Thesis of Dr Ben-Fillippo Krippendorff and focuses on a class of cell membrane receptors (Receptor Tyrosine Kinases) and their interaction with inhibitory protein drugs such as monoclonal antibodies (which are used in cancer treatment as part of chemotherapeutic regimes). The project aims at understanding how the magnitude of inhibition relates to the phenotype of the target cell and the biophysical parameters of the drug. The elucidation of these interactions may aid the design and optimization of therapeutic proteins. The analyses are based on a nonlinear ODE model for the drug-receptor-ligand interaction; some of our first results are reported in the conference articles [9,10].

Collaborators: Dr Ben-Fillippo Krippendorff (U. Cambridge), Prof Wilhelm Huisinga (U. Potsdam).

Research in Feedback Control Systems

Multivariable control

This is part of the research done with Prof Mario Salgado and in collaboration with Dr Eduardo Silva (Universidad Técnica Federico Santa María, Chile). Most of this work is about optimal control methods for multivariate systems with a particular sparsity structure. See journal papers [2-4] and conference papers [1,3,5,6,8] below.

Power electronics

As part of a research internship during 2004. See journal paper [5] and conference paper [2].

Publications

Journals

[7] D. A. Oyarzún. Optimal control of metabolic networks with saturable enzyme kinetics. IET Systems Biology, in press.
[6]D. A. Oyarzún, B. Ingalls, R. Middleton, and D. Kalamatianos. Sequential activation of metabolic pathways: a dynamic optimization approach. Bulletin of Mathematical Biology, 71(8):1851–1872, 2009. (PDF)(Link)
[5]P. Lezana, J. Rodríguez, and D. A. Oyarzún. Cascaded multilevel inverter with regeneration capability and reduced number of switches. IEEE Transactions on Industrial Electronics, 55:1059–1066, 2008. (Link)
[4]M. Salgado and D. A. Oyarzún. Double objective optimal multivariable ripple-free deadbeat control. International Journal of Control, 80(5):763–773, 2007. (PDF) (Link)
[3]M. Salgado, D. A. Oyarzún, and E. Silva. H2 optimal ripple-free deadbeat controller design. Automatica, 43(11):1961–1967, 2007. (PDF) (Link)
[2]E. Silva, D. A. Oyarzún, and M. Salgado. On structurally constrained H2 performance bounds for stable MIMO plant models. IET Control Theory & Applications, 1(4):1033–1045, 2007. (PDF) (Link)
[1]M. Salgado and D. A. Oyarzún. Basic integrated modelling: A case study. International Journal on Electrical Engineering Education, 43(3):217–231, 2006. (PDF) (Link)

Conference proceedings

[12] D. A. Oyarzún and M. Chaves. Global gene regulation in metabolic networks. Under review, 2010. (INRIA report on HAL archives PDF)
[11] D. A. Oyarzún and R. H. Middleton. Optimal adaptation of metabolic networks in dynamic equilibrium. Under review, 2010.
[10]F. López-Caamal, D. A. Oyarzún, D. Kalamatianos and J. Moreno. Control structure and limitations of biochemical networks. In Proceedings of the 2010 American Control Conference, pp. 6668–6673, Baltimore, USA. (PDF)
[9]B. -F. Krippendorff, D. A. Oyarzún and W. Huisinga. Ligand accumulation counteracts therapeutic inhibition of receptor systems. In Proceedings of Foundations of Systems Biology & Engineering (FOSBE), pp. 173–176, Denver, USA, 2009. (PDF)
[8]A. Peters, D. A. Oyarzún, E. Silva, and M. Salgado. Analytic characterization of a stabilizing feedback for LTI plants. In European Control Conference, pp. 231–235, Budapest, Hungary, 2009. (PDF)
[7]D. A. Oyarzún, B. Ingalls, R. Middleton, and D. Kalamatianos. Optimal metabolic pathway activation. In 17th IFAC World Congress, pp. 12587–12592, Seoul, Korea, 2008. (PDF)
[6]D. A. Oyarzún and M. Salgado. Optimal triangular approximation for linear stable multivariable systems. In Proceedings of 2007 American Control Conference, pp. 5158–5153, New York, USA. (PDF)
[5]D. A. Oyarzún and E. Silva. Effect of downstream feedback on the achievable performance of feedback control loops for serial processes. In Proceedings of European Control Conference, Kos, Greece, pages 1727–1733, 2007. (PDF)
[4]D. A. Oyarzún, B. Ingalls, and D. Kalamatianos. Optimal metabolic regulation by time variation of enzyme activities: a control theoretic approach. In Proceedings of Foundations of Systems Biology and Engineering, Stuttgart, Germany, pages 491–496, 2007. (PDF)
[3]D. A. Oyarzún and M. Salgado. Suboptimal triangular controller design methodology for full MIMO stable systems. In Proceedings of the 6th bi-ennial UKACC Control Conference, Glasgow, Scotland, 2006. (PDF)
[2]P. Lezana, J. Rodríguez, D. R. Oyarzún, and J. Pontt. Novel cell based on reduced single-phase active front end for multicell converters. In Proceedings of the 31st Annual Conference of the IEEE Industrial Electronics Society, Raleigh, USA, pages 733–738, 2005. (PDF)
[1]M. Salgado and D. R. Oyarzún. MIMO interactions in sampled-data systems. In Proceedings of the 16th IFAC World Congress, Prague, Czech Republic, 2005. (PDF)

Others

D. A. Oyarzún, Límites en desempeño para lazos multivariables con controladores de estructura triangular. M. Sc. Thesis, Universidad Técnica Federico Santa María, Valparaíso, Chile, 2006.
[ .pdf ] (Errata not available)
D. A. Oyarzún, A control-theoretic approach to dynamic optimization of metabolic networks. Ph.D. Thesis, National University of Ireland, Maynooth, 2010.
[ .pdf ]

Last update 01.12.2010