Modelling macromolecular networks: two meetings in Paris, July, 2002

Two meetings were recently held in Paris and Evry under the auspices of the publically-funded research/biotech agency genopole and of the Institut des Hautes Etudes Scientifiques. The first was a symposium, held July 8–11, 2002, which was devoted to ‘‘Macromolecular Networks’’, while the second was a workshop, which immediately followed the main meeting, July12–13, 2002, which was devoted to ‘‘Regulatory protein interplay and traffic on DNA’’. The Symposium focused on recent conceptual insights for identifying the dynamics of macromolecular interactions, the morphodynamics of biological structures and the nature of epigenetic processes. The Workshop concentrated on the control of macromolecular traffic on DNA and the interplay between regulating proteins acting on the same target gene. The sources of information for both were the rapidly growing amount of genomic, transcriptomic and proteomic data. Addressing these issues requires interdisciplinary approaches, a fact reflected by the variety of scientific backgrounds of both speakers and audience. In this report, we shall attempt to capture some of the spirit of these meetings, rather than trying to give a detailed summary of the findings; we apologize for any involuntary misor under-representations. Both meetings were coorganized with Paul Bourgine (CREA, CNRS/Ecole Polytechnique) and Misha Gromov (IHES). Macromolecular networks come in three major flavours: metabolic networks, where interactions mostly involve enzymatic proteins and small molecules or metabolites protein– protein interaction networks and genetic networks, where regulatory proteins interact with promoter regions on DNA. These networks were analyzed in different talks from the physiological, comparative and informational angles. The dominant view in biotechnology is that the phenotype/ genotype relationship can be solved by appropriate population genetic-statistical treatments, especially in multigenic diseases. The first speaker, David Weatherall (Univ. of Oxford), however, began by giving us a salutary tour of wellstudied monogenic diseases, thalassaemias, where this relationship still defies our full comprehension. Indeed, the findings show that even these so called monogenic diseases can behave as both polygenic conditions and environmentally triggered conditions. Evidently, even ‘‘simple’’ genetic diseases can show unwonted biological complexity. John Tyson (Virginia Polytechnic Inst.) followed this first talk and described a mathematical model of the cell cycle in fission yeast that integrates most factual observations in wild-type and mutant cells. Using dynamical systems, he analysed the cell cycle arrest points and transitions in terms of steady states and bifurcations, respectively. AdamArkin (Univ. of California at Berkeley) emphasized the interest of breaking down some of the regulatory networks into recognizable engineering functions, which can be done irrespective of the identities of their constituent genes. He described chemotaxis in neutrophil cells, where protein interactions are involved in sensing bacterial invaders and inducing actin contraction to target the movement of the cell towards bacteria. This example illustrated well a new level of complexity not previously seen in model chemotactic systems in bacteria. Stanislas Leibler (Rockefeller Univ.) discussed how spatio-temporal precision can be built by the working of genetic networks. His group’s analysis of the morphogen gradients involved in the first steps of segmental patterning in Drosophila has revealed that, in early fly development, the noise in their positional information decreases between the first and second step of the transcriptional cascade. In effect, one property of complex transcriptional networks might be their general refinement (noise reduction) through successive rounds of operation. PrzemyslawPrusinkiewicz (Univ. of Calgary) outlined the use of Lindenmayer-systems as a framework in modelling. He described recent progress on incorporating gene action into