User:J. C. Martinez-Garcia/Notebook/HMS Activities/2008/09/02

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Meeting with Walter Fontana

  • Today I meet Walter Fontana in order to get from him some insight current trends concerning the study of biological systems. The meeting was very fruitful and essentially it tourned around two main subjects: the modeling question concerning biological systems, and the interaction between evolution, robustness, evolvability and plasticity. In what follows I will expose what Iunderstand from the Fontana's exposition:
    • The granularity of the description of a biological systems, in particular the biological systems constituted by the interaction of proteins at the cellular level, conditions the applicability of modeling techniques.
    • At the cellular level, when considering the astronomical number of possible chemical species resulting from post-translational modifications, the biological processes underlying decisions are combinatorial. Because of this fact differential equations are unfeasible and meaningless as modeling tools. However, at certain levels of aggregation ODE can be useful.
    • In order to tackle the modeling problem of biological processes at the biomolecular level, computer programs seems to be the right tool. The research program pursued by Walter Fontana and his co-workers revolves around an agent-based (or rule-based) view of biological molecules and their actions. This approach is analogous in spirit to how reactions are represented in organic chemistry, but more attuned to the needs of molecular biologists. In chemistry, the internal structure of molecules is expressed in a formal language. Chemical reactions are then codified in terms of rules describing how functional groups engage in specific transformations. A rule only describes the structural context required for an interaction, leaving the rest unspecified (for example the residue of an amino acid). The Fontana team uses a formal language - Kappa, originally proposed by Vincent Danos and Cosimo Laneve - to express proteins in terms of "sites" that represent interaction capabilities. Such capabilities carry "state", like binding (as in complex formation), any number of post-translational modifications, or information about localization. Rules then formally express empirically obtained facts about protein-protein interactions. They specify the state of sites only to an extent necessary for stipulating the conditions for interaction. The philosophy of the project is to specify a system as a set of rules, analyze that set directly (deploying techniques from abstract interpretation), and use it to drive a stochastic simulation without ever writing an equation. The system of rules replaces the system of equations as the formal object to be analyzed.
    • Considering my questions on robustness, Fontana exposed to me some of his ideas concerning evolution. The discussion is summarized in the following figure: Evolutionary game.png
    • The robustness issue: when discussing with Walter about the robustness issue, I asked him if he think that biological robustness is hierarchy evolutive property, i.e. if robustness has a evolutive history. I also asked him if he think that the robustness property has something like a hierarchy associated to a link which relates the property with the level of organization. He answer me that he don't know what is the answer. It seems that he does not believe that the robustness property has a nested structure (in the nested vision the most ancient biological systems, which are something like the kernel of the living beings, are more robust -to both environmental and mutational changes-). He gave me an speculative einsteinian metaphor in order to describe the structure of the evolutionary process. <font=color"red">I MUST SEE THI METAPHOR CAREFULLY</font>.
  3. Some possible collaboration with Walter

Walter proposed me to collaborate in some specific topics. He wants to show me the Kappa system. I will contact him in some days to ask him the name of the MIT contact and to fix a date to see the way the Kappa system works.

Some comments on the meeting with David

I presented to David the simulation of the Dahl model for dynamical friction. He i interested, but he specified that his system (the reduced AKT signaling pathway) concerns the behavior in steady state. I need then a time independent model of the friction -as a possible tool to describe the hysteretical phenomenon observed in his experiments with the tumorous cells-. TO BE CONTINUED.