[Colloquium] REMINDER: Seminar Announcement: Executable Knowledge

[Ninfa Mayorga]

Computation Institute-Computational Knowledge Synthesis

Speaker: Walter Fontana, Department of Systems Biology, Harvard Medical School, Boston, MA
Date: Monday, October 3, 2011 
Time: 3:00 PM - 4:20 PM
Location: University of Chicago, Searle, Room 240A, 5735 S. Ellis Avenue

Executable Knowledge

ABSTRACT:
I will review an ongoing project aimed at developing a formal and pragmatic framework for representing and exploring the behavior of complex molecular systems of interaction, such as they occur in cellular signaling. The approach recognizes the convergence of a scientific challenge---the need for transparent models respectful of the combinatorial complexity of protein-protein interaction networks---and a knowledge representation challenge---the collation, curation, and formalization of mechanistic interaction data through which models can become open-source collaborative documents.

This is mainly a 'vision' talk, more than a technical talk, covering three facets. (1) A characterization of the problem and associated opportunities, especially the changing role of the notion of 'model' in systems biology. (2) A survey of the approach: the definition of a (site)graph rewriting language along with a suite of tools, analytics, and web infrastructure. (3) An outline of the road ahead.

This is joint work with Vincent Danos (Edinburgh), Eric Deeds (U of Kansas), Jerome Feret (ENS, Paris), Russ Harmer (Harvard & CNRS), and Jean Krivine (CNRS, Paris).

Bio:
I am a theorist and computational scientist who also developed an interest in experimental research four years ago. Yet, the experimental track on aging (in C. elegans) is not directly related to my theoretical research on molecular signaling. In an earlier phase of my trajectory as a scientist, I made several practical contributions to RNA folding by starting the so-called 'Vienna RNA package'. I also helped advance our understanding of the relation between plasticity and evolvability in the context of RNA folding, which I viewed as a proxy for a genotype-phenotype relation. With my colleagues, I coined the concept of a 'neutral network' (with a T): a mutationally connected network of sequences that share the same phenotype. The concept found experimental corroboration, and spilled over into other areas of biological research. I still pursue these themes, but I have quit doing so in the context of RNA, because I felt that the insights I had gained needed revisiting at a more complex and clinically consequential level of biological organization: molecular signaling. My resistance to bending questions to fit available tools set me on a path to seek a new approach for modeling complex systems of molecular interaction. I came to believe in a tight connection, at an abstract level, between the subject matters of computer science and biology. I found soulmates among theoretical computer scientists, especially in the field of concurrency (the formal study of systems of autonomously interacting processes). Together, we built the 'Kappa framework': a formal language for expressing mechanistic rules of protein-protein interaction, a simulation engine implementing its stochastic semantics, a suite of tools for constructing and analyzing coherent subsets of rules, and a web application for sharing and collaborating. I hope to grow this effort into a significant scientific commons. My lab consists of young scientists with a broad diversity of backgrounds an d skills including statistics, biophysics, genetics, computer science and molecular biology. We are embedded in a department (Systems Biology) whose intellectually tightly knit faculty provides a powerful living knowledge base in cell biology.



Information: Walter Fontana's CV can be found at http://fontana.med.harvard.edu/www/Documents/WF/CV/WalterFontana.pdf

If anyone would like to meet with Walter Fontana outside the talk, please contact James Evans (jevans at uchicago.edu)

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