MATBRAC is a project financed by Institut des Systemes Complexes Paris Ile-de-France in the Appel d'offre a idees 2007 program.

Project resume

One of the most fruitful suggestion in modeling biological systems is that the feasible model designs should be robust. This principle is justified by a universal observation that biological systems stably perform their functions in highly variable external (environment) and internal (cellular content, including genetic variations) conditions. Being necessary for stable normal cell functioning, biological robustness poses problems for intervention strategies, in particular, in the treatment of various systemic diseases such as immune diseases or cancer.

The objectives of this project are

1. develop mathematically well-defined concepts of biological robustness and to develop it more specifically to the biology of cancer
2. develop and implement theoretical tools for identification, classification and correction of robust behavior in mathematical models of molecular mechanisms important for cancer
3. perform several case studies of biological robustness in mathematical models of signal transduction pathways controlling cell cycle and apoptosis: NfkB pathway, TGFb pathway, RB/E2F pathway
4. use available high-throughput data on genome structure and transcriptome of tumor samples to validate our conclusions
5. develop our conclusions up to testable hypotheses, and as far as it will be possible (if other sources of funding will be obtained), verify them in a laboratory experiment

Full project application can be downloaded here.

Project participants

• Institut Curie
  1. Andrei Zinovyev (coordinator), Service Bioinformatique, UMR900 INSERM/Curie/Mines
  2. Emmanuel Barillot, UMR900 INSERM/Curie/Mines
  3. Francois Radvanyi, UMR 144 CNRS/Institut Curie
  4. Olivier Dellatre, Unite 830 INSERM/Institut Curie
  5. Laurence Calzone, UMR900 INSERM/Curie/Mines
• IRMAR
  1. Ovidiu Radulescu, Univ.Rennes, INRIA
  2. Tatiana Baumuratova, Univ.Rennes
• Universite Paris 7
  1. Alain Lilienbaum, EA300

Short bibliography

1. Radulescu O., Zinovyev A., Lilienbaum A. Model reduction and model comparison for NFkB signaling. In Proceedings of Foundations of Systems Biology in Engineering, September 2007, Stuttgart, Germany (PDF)
2. Gorban A. and Radulescu O. Dynamical robustness of biological networks with hierarchical distribution of time scales IET Syst Biol. 2007 Jul;1(4):238-46. (PDF)
3. Radulescu O., Gorban A., Vakulenko S., Zinovyev A. Hierarchies and modules in complex biological systems. Proceedings of ECCS'06 (PDF)
4. Gorban A., Karlin I., Zinovyev A. Invariant grids: method of complexity reduction in reaction networks. 2005. ComPlexUs 2004-05;2:110-127 (PDF)
5. Kitano H. (2004) Cancer as a robust system: implications for anticancer therapy. Nature Reviews Cancer 4, 227-235 (PDF)
6. Carlson JM, Doyle J. Complexity and robustness. PNAS 2002 Feb 19;99 Suppl 1:2538-45. (PDF)

News and principal results

25/02/08: The project web-site was created

19/03/08: Prof. Hiroaki Kitano visited the Bioinformatics lab of Institut Curie. In the discussion, possible collaboration with his team in the field of mathematical theory of biological robustness was considered.

03/06/08: Ovidiu Radulescu made a visit to the group of Prof. Upi Bhalla in Bangalore (India) with the objective of establishing a collaborative project

14/04/08: A manuscript by O.Radulescu, A.Gorban, A.Zinovyev, A.Lilienbaum. "Robust simplifications of multiscale models in systems biology" is submitted

24/06/08: An oral presentation "METHOD FOR COMPLEXITY REDUCTION AND MODEL COMPARISON WITH APPLICATION TO NFêB SIGNALLING" at BGRS-2008 was made by A.Zinovyev

20/08/08: A project on studying modules and robust behaviour of RB/E2F pathway is accepted for funding by ANR in the SYSCOMM program

23-29/08/08: A poster "Robust model simplifications in multiscale systems" was presented at ICSB-2008

27/08/08: A roadmap for collaboration with the group of Prof. Hiroaki Kitano was defined

14/10/08: The paper O.Radulescu, A.Gorban, A.Zinovyev, A.Lilienbaum. "Robust simplifications of multiscale biochemical networks" is accepted and published. Link

20/11/08: MATBRAC meeting was hold. 12 persons participated, 4 presentations were made

MATBRAC meeting presentations:

1. Andrei Zinovyev "Introduction into MATBRAC objectives"
2. Annick Lesne "Biological robustness: what do we learn from (mathematical) physics ?" based on A. Lesne (2008) Robustness: confronting lessons from physics and biology, Biological Reviews 83, 509-532 (with permission of Biological Reviews, Cambridge Philosophical Society and Blackwell Publishing)
3. Francois Radvanyi "One biologist's view on robustness"
4. Ovidiu Radulescu Mathematical framework for studying biological robustness
5. Marie-Anne Felix "Robustness and evolution of Caenorhabditis vulva precursor cell fate patterning"