Delphine Ropers
Research scientist ("Chargée de recherche") INRIA
INRIA Rhône-Alpes
655 avenue de l'Europe, Montbonnot
38334 Saint Ismier CEDEX
France
Tel. +33 4 76 61 53 72
Fax +33 4 76 61 54 08
Secretary (Françoise de Coninck)
Tel. +33 4 76 61 53 63
Delphine.Ropers@inrialpes.fr
http://www-helix.inrialpes.fr/
Curriculum vitae
I was born on November 29th, 1975 near Nancy. I received a B.Sc. in Biochemistry and a M.Sc. in Microbiology, Enzymology, and Nutrition from the Henri Poincaré University in Nancy. In the course of this training, I developed a strong interest for pluridisciplinarity and I decided to develop my research activites in the fields of molecular biology and bioinformatics.
In 1998, I started my PhD thesis in the Laboratory of RNA Maturation and Molecular Enzymology headed by Christiane Branlant (Centre National de la Recherche Scientifique - Université Nancy I), while collaborating with the MODBIO research group at Loria (Institut National de Recherche en Informatique et en Automatique, research unit INRIA Lorraine), headed at that time by Alexander Bockmayr. I studied, both by experiments and mathematical modeling, the splicing regulation of the human immunodeficiency virus RNA.
After having obtained my PhD in 2003, I joined the research unit INRIA Rhône-Alpes as a post-doctoral researcher in the HELIX research group, headed by Alain Viari. In 2006, I have been recruited as a research scientist (chargé de recherche) at INRIA. I continue working in the same research group on the mathematical modeling of regulatory networks in bacteria, in particular, the model bacterium Escherichia coli.
Current research
The adaptation of living organisms to their environment is controlled at the molecular level by large and complex networks of genes, mRNAs, proteins, metabolites, and their mutual interactions. Molecular biology has been quite successful in dissecting these networks down to the molecular details of the interactions. However, in order to understand the overall behavior of an organism, we must complement molecular biology with a more global view of cellular functioning, by means of mathematical and computational tools. The dynamic analysis of cellular interaction networks provides a means to tackle this question, by constructing mathematical models derived from experimental data on the network structure, and using simulation tools to predict the behavior of the system under a variety of conditions.
Following this methodology, I analyze the regulatory network controlling the adaptation and survival of the gut bacterium Escherichia coli to environmental stress conditions. Understanding environmental influences helps one to explain the distribution of microorganisms in nature and makes it possible to devise methods for controlling or enhancing microbial activities. Even though E. coli is one of the best studied organisms, it is currently little understood how stress signals are sensed and propagated throughout the network, so as to enable the bacterium to respond in an adequate way.
To address these questions, I develop kinetic models of the network, and study them by means of classical analysis and simulation tools. For large systems, this approach is difficult to apply, due to the lack of reliable values for the parameters and initial conditions. Moreover, the models consist of a large number of variables, are strongly nonlinear, and include different time scales. To deal with these problems, I use (quasi-steady-state and piecewise-linear) approximations that preserve the capacity of the models to account for essential dynamic properties of the system. This allows to analyze the [qualitative dynamics>art338] of the stress response network of E. coli and predict the response of the bacterium to nutritional stress.
The experimental verification of the model predictions is carried out in the Laboratory of Adaptation and Pathogenesis of Microorganisms (LAPM) at the Joseph Fourier University in Grenoble, with whom I work in close collaboration, in particular with Hans Geiselmann, Dominique Schneider, and Corinne Pinel. I also collaborate with Irina Mihalcescu from the Laboratoire de Spectrométrie Physique (LSP). From a methodological point of view, the application of mathematical tools to the dynamic analysis of regulatory networks open new questions, which opens up further methodological developments. I work on these aspects in close collaboration with Hidde de Jong (INRIA Rhône-Alpes), Valentina Baldazzi (INRIA Rhône-Alpes), Daniel Kahn (INRIA Rhône-Alpes), Michel Page (INRIA Rhône-Alpes; Université Pierre Mendès France, Grenoble), and Jean-Luc Gouzé (INRIA Sophia-Antipolis).
Recent presentations
 Modeling of bacterial regulatory networks, IXXI Seminar "Towards a science of complex systems", November 2007, Grenoble (invited talk).
Qualitative simulation of the carbon starvation response in Escherichia coli, Seminar of IGM at Orsay University, September 2007, Orsay (invited talk).
Development and experimental validation of piecewise affine models of carbon starvation response in Escherichia coli, HYGEIA summer school on Hybrid Systems Biology, July 2007, Siena, Italy.
Qualitative simulation of the carbon starvation response in Escherichia coli, Technical University Inesc-ID, May 2007, Lisbon, Portugal (invited talk).
Qualitative simulation of the carbon starvation response in Escherichia coli, Spring School on Dynamical Modelling of Biological Regulatory Networks, April 2007, Les Houches, France (invited talk).
Qualitative simulation of the carbon starvation response in Escherichia coli, Seminar of the SAFE Consortium (European Association for Food Safety), March 2006, Brussels, Belgium (invited talk).
Qualitative simulation of the carbon starvation response in Escherichia coli, Systems Biology Workshop, February 2006, Jouy-en-Josas, France (invited talk).
Modeling and simulation of genetic regulatory networks: The nutritional stress response in Escherichia coli. Presentation given together with Hidde de Jong during the "4ème Ecole Thématique de Biologie Végétale : Biologie Intégrative" (CNRS/INRA), October 2005, Batz-sur-Mer, France (invited talk).
Genetic Network Analyzer: A tool for the qualitative modeling and simulation of genetic regulatory networks. Tutorial on GNA given in the framework of the Taiwanese Bioinformatics conference BIT2005, September 2005, Tainan (invited talk).
Piecewise-linear Models of genetic regulatory networks: Application to the analysis of the carbon starvation response in Escherichia coli, European Conference on Mathematical and Theoretical Biology ECMTB 2005, July 2005, Dresden, Germany.
Qualitative simulation of the carbon starvation response in Escherichia coli: Utilization of the reporter genes gfp and lux, JOBIM satellite meeting, July 2005, Lyon, France (invited talk).
Qualitative simulation of the nutritional stress response in Escherichia coli. Presentation given together with Hidde de Jong during the seminar of INRA "Programmes de génomique animale, végétale et des microorganismes", December 2004, Paris, France (invited talk).
Qualitative simulation of the nutritional stress response in Escherichia coli, Seminar Algorithmics and Biology, November 2004, Lyon, France (invited talk).
Qualitative modelling of the dynamics of genetic regulatory networks: II. Piecewise-linear differential equations. Tutorial given together with Hidde de Jong during the workshop on the Modelling of Metabolic and Genetic Networks at the Fifth International Conference on Systems Biology (ICSB), October 2004, Heidelberg, Germany.
Qualitative simulation of the nutritional stress response in Escherichia coli, JOBIM satellite meeting, July 2004, Montreal, Canada.
Courses
I have given master courses in bioinformatics, in particular on the modeling and simulation of genetic regulatory networks, at the Claude Bernard University in Lyon, at the Joseph Fourier University in Grenoble, and in the Ph.D. Program in Computational Biology of the Instituto Gulbenkian de Ciencia in Lisbon (Portugal). The latest version of these courses, providing a general introduction and an overview of the qualitative modeling and simulation approach, are available.
Organizational and other activities
In the framework of the French working group VICANNE, I organized with Hidde de Jong a meeting on integrated models of gene regulation and metabolism in Grenoble (May 2004). I have been on the program committee of the Journées Ouvertes Biologie Informatique Mathématiques (JOBIM) 2007, in the steering committee of the Seminar on Modeling in the Life Sciences SEMOVI, and in the scientific board of the Complex Systems Institute (IXXI).
Selected publications
2008
P.T. Monteiro, D. Ropers, R. Mateescu, A.T. Freitas, H. de Jong (2008), Temporal logic patterns for querying dynamic models of cellular interaction networks, Bioinformatics, in press. Special issue ECCB-2005.
D. Ropers, H. de Jong, J. Geiselmann (2008), Mathematical modeling of genetic regulatory networks: Stress responses in Escherichia coli, P. Fu, M. Latterich, S. Panke, Systems and Synthetic Biology, Wiley & Sons, in press.
2007
D. Ropers, H. de Jong, J.-L. Gouzé, M. Page, D. Schneider, J. Geiselmann, Piecewise-linear models of genetic regulatory networks: Analysis of the carbon starvation response in Escherichia coli. Proceedings of ECMTB 2005, Mathematical Modeling of Biological Systems, Volume I. A. Deutsch, L. Brusch, H. Byrne, G. de Vries and H.-P. Herzel (eds), Birkhäuser, Boston, 83-96.
D. Ropers, H. de Jong, J. Geiselmann (2007), Modélisation de la réponse au stress nutritionnel de la bactérie Escherichia coli, Biofutur, 275:36-39.
G. Batt, H. de Jong, J. Geiselmann, J.-L. Gouzé, M. Page, D. Ropers, T. Sari, D. Schneider (2007), Analyse qualitative de la dynamique de réseaux de régulation génique par des modèles linéaires par morceaux, Technique et Science Informatique, 26(1-2):11-45.
G. Batt, D. Ropers, H. de Jong, M. Page, J. Geiselmann (2007), Symbolic reachability analysis of genetic regulatory networks using qualitative abstractions, Technical Report INRIA, RR-6136.
2006
H. de Jong, D. Ropers (2006), Strategies for dealing with incomplete information in the modeling of molecular interaction networks, Briefings in Bioinformatics, 7(4):354-363.
H. Hallay, N. Locker, L. Ayadi, D. Ropers, E. Guittet, C. Branlant (2006), Biochemical and NMR study on the competition between proteins SC35, SRp40, and heterogeneous nuclear ribonucleoprotein A1 at the HIV-1 Tat exon 2 splicing site, Journal of Biological Chemistry, 281(48):37159-74.
D. Ropers, H. de Jong, M. Page, D. Schneider, J. Geiselmann (2006), Qualitative simulation of the carbon starvation response in Escherichia coli. BioSystems, 84(2):124-152.
G. Batt, R. Casey, H. de Jong, J. Geiselmann, J.-L. Gouzé, M. Page, D. Ropers, T. Sari, D. Schneider (2006), Qualitative analysis of the dynamics of genetic regulatory networks using piecewise-linear models. E. Pecou, S. Martinez, A. Maass (eds.), Mathematical and Computational Methods in Biology, Editions Hermann, Paris, 206-238.
H. de Jong, D. Ropers (2006), Qualitative approaches towards the analysis of genetic regulatory networks, Z. Szallasi, V. Periwal, J. Stelling (eds), System Modeling in Cellular Biology: From Concepts to Nuts and Bolts, MIT Press, Cambridge, MA, 125-148.
2005
G. Batt, D. Ropers, H. de Jong, J. Geiselmann, R. Mateescu, M. Page and D. Schneider (2005), Validation of qualitative models of genetic regulatory networks by model checking: Analysis of the nutritional stress response in Escherichia coli. Bioinformatics, 21(Suppl 1):i19-i28, special issue ISMB-2005. Also in G. Perrière, A. Guénoche and C. Geourjon, eds., Working Notes of the Journées Ouvertes Biologie, Informatique et Mathématiques (JOBIM'05), 471-482, Lyon, France.
G. Batt, D. Ropers, H. de Jong, J. Geiselmann, R. Mateescu, M. Page, D. Schneider (2005), Analysis and verification of qualitative models of genetic regulatory networks: A model-checking approach. Proceedings of the Nineteenth International Joint Conference on Artificial Intelligence (IJCAI-05), Morgan Kauffman, San Francisco, CA., 370-375.
G. Batt, H. de Jong, J. Geiselmann, M. Page, D. Ropers, D. Schneider (2005), Qualitative analysis and verification of hybrid models of genetic regulatory networks: Nutritional stress response in Escherichia coli. M. Morari, L. Thiele (eds), Hybrid Systems: Computation and Control, HSCC 2005, Lecture Notes in Computer Science 3414, Springer-Verlag, Berlin, 134-150.
H. de Jong, D. Ropers, C. Chaouiya, D. Thieffry (2005), Modélisation, analyse et simulation de réseaux de régulation génique, Biofutur, 252: 36-40.
2004
D. Ropers, H. de Jong, M. Page, D. Schneider, J. Geiselmann (2004), Qualitative simulation of the nutritional stress response in Escherichia coli, INRIA RR-5412.
G. Batt, H. de Jong, J. Geiselmann, M. Page, D. Ropers, D. Schneider (2004), Symbolic reachability analysis of genetic regulatory networks using qualitative abstraction, INRIA RR-5362.
D. Eveillard, D. Ropers, H. de Jong, C. Branlant, A. Bockmayr (2004), A multi-scale constraint programming model of alternative splicing regulation, Theoretical Computer Science, 135(1): 3-24.
D. Ropers, L. Ayadi, R. Gattoni, S. Jacquenet, L. Damier, C. Branlant, J. Stévenin (2004), Differential effects of the SR proteins 9G8, SC35, ASF/SF2 and SRp40 on the utilization of the A1 to A5 splicing sites of HIV-1 RNA, Journal of Biological Chemistry, 279(29): 29963-29973.
Eveillard D., Larhlimi A., Ropers D., Billaut S., Peyrefitte S. (2004), KOALAB: A new method for regulatory motif search. Illustration on alternative splicing regulation in HIV-1. Proceedings of the Journées Ouvertes Biologie Informatique Mathématiques, JOBIM 2004, Montreal, Canada.
2003
D. Ropers (2003), Experimental study of the SR protein role in the splicing regulation of the HIV-1 virus RNA, responsible of the human immunodeficiency, and mathematical modeling of these regulations, PhD thesis in molecular biology, University Henri Poincaré, Nancy I.
D. Eveillard, D. Ropers, H. de Jong, C. Branlant, A. Bockmayr (2003), A Multi-Site Constraint Programming Model of Alternative Splicing Regulation, INRIA RR-4830.
D. Eveillard, D. Ropers, H. de Jong, C. Branlant, A. Bockmayr (2003), Multiscale modeling of alternative splicing regulation, C. Priami (ed.), Computational Methods in Systems Biology, CMSB-03, Lecture Notes in Computer Science 2602, Springer-Verlag, Berlin, 75-87.
2001
S. Jacquenet, D. Ropers, P. Bilodeau, L. Damier, A. Mougin, M. Stoltzfus, C. Branlant (2001), Conserved stem-loop structures in the HIV-1 RNA region containing the A3 3' splice site and its cis-regulatory element: possible involvement in RNA splicing, Nucleic Acids Research, 29(2): 464-478. |
