Computational Systems Biophysics
 

 

Contact

Jose M. G. Vilar
Ikerbasque Professor

Biophysics Unit (CSIC-UPV/EHU)
Department of Biochemistry and Molecular Biology
University of the Basque Country
P.O. Box 644, 48080 Bilbao, Spain

Phone: (+34) 94 601 3450 | Fax: (+34) 94 601 3360
E-mail: | Web: http://www.vilarlab.org

Scientific Career

Degrees 

• 1995: B.S./M.S. in Physics, University of Barcelona
• 1998: Ph.D. in Physics, University of Barcelona               
  

Appointments

• 1996-1998: Predoctoral Research Fellow,  Department of Fundamental Physics, University of Barcelona
• 1998-2000: Postdoctoral Research Fellow, Departments of Physics and Molecular Biology, Princeton University
• 2000-2001: Research Associate, Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University
• 2001-2003: Postdoctoral Associate, The Rockefeller University
• 2003-2004: Visiting Investigator, Memorial Sloan-Kettering Cancer Center
• 2004-2008: Assistant Member & Head of Laboratory, Computational Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center
• 2005-2008: Assistant Professor of Physiology, Biophysics, and Systems Biology, Weill Graduate School of Medical Sciences, Cornell University.
• 2008-Present: Ikerbasque Professor, Department of Biochemistry and Molecular Biology, University of the Basque Country

Research

The traditional experimental approach to the study of the functioning of cells has been remarkably successful at identifying cellular components and their interactions. Current automated technologies have brought the cartoon-like representations of cellular processes to exponentially growing webs of nodes and links that seem as close to completion as ever. The complexity of the emerging picture, however, makes it clear that all this information by itself is not enough to truly understand processes such as cancer. In order to piece back together all the genetic, biochemical, molecular, and structural information into a physiologically relevant description of the cell, one needs "constructive" methods. Computational modeling has emerged as a promising tool for transforming molecular detail into a more integrated form of understanding complex behavior.

We use computational and mathematical modeling to study biological networks that are relevant to cancer. We are interested, not only in the interactions between cellular components, but also in the resulting cellular behavior and its integration into the physiological context of an organism. We study computationally how mutations affect the molecular properties of the cellular components; how the mutated components affect different pathways; and how these modified pathways confer cell-growth advantages during tumor progression and metastasis. Having a global view of all these processes and their effects through all relevant levels of biological organization is crucial to identify and characterize the key control elements of the system.

We are currently working on:

• Gene regulation (RXR and other nuclear hormone receptors)
• Signal transduction (EGF and TGF-β pathways)
• Control of cell growth and death (Bcl-2/Bax in metabolism and apoptosis)

We are also developing new computational approaches to determine, capture, and use the relevant biological information. We are especially interested in stochastic analyses and in multilevel and multiscale methods.

Publications

Press commentaries on our research:

Articles in journals

• L. Saiz and J. M. G. Vilar, Protein-protein/DNA interaction networks: versatile macromolecular structures for the control of gene expression, IET Systems Biology 2, 247-255 (2008).
• J. M. G. Vilar and J. M. Rubi, Failure of the Work-Hamiltonian Connection for Free-Energy Calculations, Phys. Rev. Lett. 100, 020601 (2008).
• L. Saiz and J. M. G. Vilar, Ab initio thermodynamic modeling of distal multisite transcription regulation, Nucleic Acids Research, 36, 726-731 (2008).
• M. H. Vainstein, J. M. Rubi and J. M. G. Vilar, Stochastic population dynamics in turbulent fields, Eur. Phys. J. ST 146, 177-187 (2007).
• L. Saiz and J. M. G. Vilar, Multilevel deconstruction of the in vivo behavior of looped DNA-protein complexes, PLoS One, 2(4): e355. doi:10.1371/journal.pone.0000355 (2007).
• W.Y. Shou, S. Ram, and J. M. G. Vilar, Synthetic cooperation in engineered yeast populations, Proc. Natl. Acad. Sci. USA 104, 1877-1882 (2007).
• J. M. G. Vilar and L. Saiz, Multiprotein DNA looping, Phys. Rev. Lett. 96, 238103 (2006).
• L. Saiz and J. M. G. Vilar, DNA looping: the consequences and its control, Curr. Opin. Struct. Biol. 16, 344-350 (2006).
• L. Saiz and J. M. G. Vilar, Stochastic dynamics of macromolecular-assembly networks, Nature/EMBO Molecular Systems Biology 2, 2006.0024, doi:10.1038/msb4100061 (2006).
• J. M. G. Vilar, Modularizing gene regulation, Nature/EMBO Molecular Systems Biology 2, 2006.0016, doi:10.1038/msb4100058 (2006).
• J. M. G. Vilar, R. Jansen, and C. Sander, Signal processing in the TGF-β superfamily ligand-receptor network, PLoS Comput. Biol. 2(1): e3 (2006).
• L. Saiz, J. M. Rubi, and J. M. G. Vilar, Inferring the in vivo looping properties of DNA, Proc. Natl. Acad. Sci. USA 102, 17642-17645 (2005).
• D. Reguera, J. M. Rubi, and J. M. G. Vilar, The Mesoscopic Dynamics of Thermodynamic Systems, J. Phys. Chem. B 109, 21502-21515 (2005).
• J. M. G. Vilar and L. Saiz, DNA looping in gene regulation: From the assembly of macromolecular complexes to the control of transcriptional noise, Curr. Opin. Genet. Dev. 15, 136-144 (2005).
• E. Korobkova, T. Emonet, J. M. G. Vilar, T. S. Shimizu, P. Cluzel, From molecular noise to behavioural variability in a single bacterium, Nature 428, 574-578 (2004). 
• J. M. G. Vilar and S. Leibler, DNA looping and physical constrains on transcription regulation, J. Mol. Biol. 331, 981-989 (2003).
•  J. M. G. Vilar, C. C. Guet, and S. Leibler, Modeling network dynamics: the lac operon, a case study, J. Cell Biol. 161, 471-476 (2003).
• J. M. G. Vilar, R. V. Solé, and J. M. Rubí, On the origin of plankton patchiness, Physica A 317, 239-246 (2002).
• José M. G. Vilar, Hao Yuan Kueh, Naama Barkai, and Stanislas Leibler, Mechanisms of noise-resistance in genetic oscillators, Proc. Natl. Acad. Sci. USA 99, 5988-15992 (2002). 
• J. M. G. Vilar and J. M. Rubí, Thermodynamics "beyond" local equilibrium,  Proc. Natl. Acad. Sci. USA 98, 11081-11084 (2001). 
• J. M. G. Vilar and J. M. Rubí, Noise suppression by noise, Phys. Rev. Lett. 86, 950-953 (2001). 
• L. Saiz, J. M. G. Vilar, and J. M. Rubí, Field-induced force-suppression in ferromagnetic colloids, Physica A 293, 51-58 (2001).
• J. M. G. Vilar and J. M. Rubí, Ordering periodic spatial structures by non-equilibrium fluctuations, Physica A 277, 327-334 (2000).
• J. M. Rubí and J. M. G. Vilar, The Rheology of Field-Responsive Suspensions, J. Phys.: Cond. Matter  12, A75-A84 (2000).
• A. Pérez-Madrid, T. Alarcón, J.M.G. Vilar, and J. M. Rubí, Mesoscopic Approach to the "Negative'' Viscosity Effect in Ferrofluids, Physica A 270, 403-412 (1999).
• J. M. G. Vilar, R. V. Solé, and J. M. Rubí, Noise and Periodic Modulations in Neural Excitable Media, Phys. Rev. E  59, 5920-5928 (1999).
• J. M. G. Vilar and J. M. Rubí, Scaling Concepts in Periodically Modulated Noisy Systems, Physica A 264, 1-14 (1999).
• J. M. G. Vilar, G. Gomila and J. M. Rubí, Stochastic Resonance in Noisy Nondynamical Systems, Phys. Rev. Lett. 81, 14-17 (1998).
• J. M. G. Vilar and R. V. Solé, Effects of Noise in Symmetric Two-Species Competition, Phys. Rev. Lett. 80, 4099-4102 (1998).
• J. M. G. Vilar and J. M. Rubí, Effect of the Output of the System in Signal Detection, Phys. Rev. E 56, 32R-35R (1997).
• J. M. G. Vilar and J. M. Rubí, Stochastic Multiresonance, Phys. Rev. Lett. 78, 2882-2885 (1997). 
• J. M. G. Vilar and J. M. Rubí, Spatiotemporal Stochastic Resonance in the Swift-Hohenberg Equation, Phys. Rev. Lett. 78, 2886-2889 (1997).
• José M. Gómez-Vilar and Ricard V. Solé, On cellular automata models for quantum systems, J. Phys. A 29, 8169 -8171 (1996).
• J. M. G. Vilar, A. Pérez-Madrid, and J. M. Rubí, Stochastic Resonance in a Dipole, Phys. Rev. E 54, 6929-6932 (1996).
• J. M. G. Vilar and J. M. Rubí, Divergent Signal-to-Noise Ratio and Stochastic Resonance in Monostable Systems, Phys. Rev. Lett. 77, 2863-2866 (1996).

Book chapters

• J. M. G. Vilar and J. M. Rubí, Scaling of Noise and Constructive Aspects of Fluctuations, in Lecture Notes in Physics: "Stochastic Processes in Physics", J. Freund and T. Pöschel, eds., Springer Verlag (Berlin, Heidelberg 2000), Vol. 557: pp. 121-130 (2000).

Books

D. Reguera, J. M. G. Vilar, and J. M. Rubí (eds.), Statistical Mechanics of Biocomplexity, Lecture Notes in Physics (Springer Verlag, Berlin 1999).

Presentations

Upcoming invited talks

• TBD. Workshop on Cellular Decision Making, June 2008, Toronto (Canada).
• Signal processing in the TGF-β superfamily ligand-receptor network. Conference on Systems Biology of Mammalian Cells, May 2008, Dresden (Germany).

Selected invited talks

• Stochastic dynamics of protein-DNA complexes. Workshop on Deconstructing Biochemical Networks, September 2007, Montreal (Canada).
• Stochastic dynamics of protein-DNA complexes. Information Processing in Cellular Signaling and Gene Regulation, August 2007, Santa Fe (New Mexico).
• Inferring the in vivo looping properties of DNA. Third international conference on Multiscale Materials Modeling, September 2006, Freiburg (Germany).
• Computational Modeling of the TGF-β Superfamily Ligand-Receptor Network. British Society for Developmental Biology Autumn Meeting: Signal Transduction and Integration in Embryonic Development, Sept 2006, Dundee (UK).
• Stochastic dynamics of protein-DNA complexes. Workshop on Nanomechanics of Biomolecules, August 2006, Ascona (Switzerland).
• Macromolecular assembly on looped DNA. ICAM workshop on "Chromatin Dynamics, Gene Regulation and Silencing", August 2006, Snowmass (Colorado).
• Stochastic Dynamics of Macromolecular-Assembly Networks. XX Sitges Conference on Statistical Mechanics. Physical Biology: from Molecular Interactions to Cellular Behavior, June 2006, Sitges, Barcelona (Spain). 
• Stochastic Dynamics of Macromolecular-Assembly Networks. Systems Biology Discussion Group, New York Academy of Sciences, November 2005, New York (New York). 
• Stochastic Dynamics of Macromolecular-Assembly Networks. ISQBP Gilda Loew Memorial Meeting, October 2005, Staten Island (New York).
• Mechanisms of Noise-resistance in Genetic Oscillators. SIAM Conference on the Life Sciences, July 2004, Portland (Oregon).
• Mathematical analysis of gene circuits. Conference on Mathematical Modelling of Plant Development and Gene Networks, University of Warwick, May 2004, Coventry (United Kingdom).
• Modeling the Networks of the Cell: Molecular, Cellular, and Population Levels. Workshop on Biological Information and Statistical Physics, July 2003, Dresden (Germany).
• Modeling Noise, Switches and Clocks. Workshop on Dynamics, Adaptation and Fluctuations in Bio-networks, KITP, University of California, March 2003, Santa Barbara (California).
• Noise in the cell: from molecular mechanisms to populations via network design. Annual American Physical Society March Meeting, March 2002, Indianapolis (Indiana).
• Networking with noise at the molecular, cellular, and population level. Gordon Research Conference on Bioinformatics: From inference to Predictive Models, August 2001, Tilton (New Hampshire).
• Modules of modules: from molecular interactions to cell populations. Workshop on Design and Control of Biochemical Networks, June 2001, Leiden (The Netherlands).
• Ordering Periodic Spatial Structures by Noise. Workshop on Fluctuations Far From Equilibrium: Noise Induced Transport, April 1998, Dresden (Germany).

People

Current

Jose Vilar (Ikerbasque Professor)

Want to join? See opportunities below!

Former (VilarLab at Memorial Sloan-Kettering Cancer Center, 2004-2008)

Leonor Saiz (Postdoc, 2004-2007)

Wenying Shou (Postdoc, 2006-2007)

Anamika Sarkar (Postdoc, 2004-2005)

Ori Weitz (Rotation Student, Tri-i CBM program, 2006)
Pawel Kocieniewski (Rotation Student, Tri-i CBM program, 2007)
Fan Xia (Rotation Student, PBSB program, 2007)
Ricky Chachra (Rotation Student, PBSB program, 2008)
Igor Segota (Rotation Student, PBSB program, 2008)

Opportunities

There are openings for Graduate Students and Postdoctoral Researchers. To apply please contact Jose Vilar at