24. – 29. Juni 2001, Dagstuhl Seminar 01261
Information and Simulation Systems for the Analysis of Gene Regulation and Metabolic Pathways
Auskunft zu diesem Dagstuhl Seminar erteilt
Molecular Biology and Biotechnology have begun to focus sharply on the problem of gene regulation. This problem is inescapable, because no open reading frame (ORF) will be expressed without the appropriate regulatory sequences. Moreover, some genes code for proteins whose function is to turn other genes on and off. Groups of these genes form networks with complex behaviors. These networks control other genes whose protein products catalyze specific biochemical reactions, and the small molecules which are substrates or products of these reactions can in turn activate or deactivate proteins which control transcription or translation. For that reason, gene regulation can be said to indirectly control biochemical reactions in cellular metabolism, and cellular metabolism itself exerts control on gene expression.
For these reasons, the interdependent biochemical processes of metabolism and gene expression can and should be interpreted and analyzed in terms of complex dynamical networks. Hence modeling and simulation are necessary. Two earlier Dagstuhl seminars (1995 and 1998) have already dealt with modeling and simulation of biochemical networks. Both sought to bridge two divides by both bringing together scientists in the disciplines of gene regulation and metabolic pathways, and within and across both of these areas bringing together experimentalists and theoreticians. Often there had been little previous contact among these groups, but clearly the integration of metabolic and gene expression models as well as the cooperation of theorists and experimentalists is essential in order to solve these complex problems.
Apart from theoreticians and experimentalists, a third group has emerged since 1995 which is centered around databases and the internet. Many Molecular Biologists turned towards informatics and systematically collected results relating to specific problems. These data have been and will be stored systematically in specific databases, which nowadays are accessible via Internet. Recently many firms have been founded which provide data essential for the solution of scientific and industrial problems, and even more importantly the corresponding infrastructure. As a result, there are data bases available via the Internet for all known sequenced genes (e.g. EMBL), proteins (e.g. SWISS-Prot, PIR, BRENDA), transcription factors (TRANSFAC), biochemical reactions (KEGG) and signal induction reactions (TRANSPATH, GeneNet). Beyond databases, simulators for metabolic networks which employ most of the currently popular modeling methods are also available via the Internet. In addition to the classical methods of differential equations, discrete methods have become quite important. Examples are the object-oriented approach, rule-based systems, Petri Nets, graphs, and Boolean nets.
These recently implemented tools on the Internet are the basic components of the informatic and analytical infrastructure of biotechnology. Clearly the next evolutionary stage of development will be the implementation of integrated molecular information systems (SRS, ...). The first step to reach that goal is the integration of databases under a specific biological perspective. The next step will be user-defined molecular information fusion.
This hereby proposed Dagstuhl-Seminar aims at evaluating and enhancing that hot topic. Up to now, there are no standard tools available in order to successfully separate both methods and data bases. Exactly for that reason it is imperative to develop uniform intersections at this stage. To discuss properties of these intersections will be one major issue of this seminar. Therefore databases have to be adjusted to meet the needs of both biologists and modelers. Another issue will be the measurement of the kinetics and biochemical mechanisms of gene expression, and the opportunities afforded by proteomics research must also be included. In order to assure a productive and useful outcome in the development of the informatics infrastructure of the future, it is essential for developers and operators of databases as well as modelers of the new information systems' generation to take into account the needs of potential users. Thus geneticists and biochemists who work in laboratories will further specify those standards.
In advance of this proposed seminar, two Dagstuhl-Seminars and a Summer School (http://wwwiti.cs.uni-magdeburg.de/iti_bm/ibss/) have been held. All three meetings had been supported financially by the Volkswagen- Foundation by means of examination. Please note, that the International Summer School held in Magdeburg in September 1999 was supported substantially by the Volkswagen-Foundation.
On the basis of those experiences, we do not suggest a sequence of lectures or demonstrations but rather to focus on the discussion of issues like implementation of standards (see above) or comparison of various models. The motivation is to emphasize key issues which are of interest for every participant, with fewer presentations. On the other hand, specific questions will be discussed more efficiently in smaller workshops. Hence outcomes from this workshops can be presented for all at a final meeting.