Multiple Aspects of DNA and RNA: from Biophysics to Bioinformatics

In August 2004, the Ecole de Physique des Houches hosted a Summer School dedicated to biological, physical and computational aspects of nucleic acids. Central to vital processes, these biological molecules have been experimentally studied by molecular biologists for five decades since the discovery of the structure of DNA by J. Watson and F. Crick in 1953. Recent progresses, such as the development of DNA arrays, manipulations at the single molecule level, the availability of huge genomic databases, have foster the need for theoretical modeling. In particular, a global understanding of the structure and function of DNA and RNA require the concerted development and application of proper experimental and theoretical approaches, involving methods and tools from different disciplines, including physics. The aim of this Summer School was precisely to provide a comprehensive overview of these issues at the interface between physics, biology and information science.

The Summer School encompassed three main sections:

1) Biochemistry and Biology of DNA/RNA;

2) Biophysics: from Experiments to modeling and theory;

3) Bioinformatics.

The present book follows the same organization, and is mainly intended to advances graduate students or young researchers willing to acquire a broad inter-disciplinary understanding of the multiple aspects of DNA and RNA.

The first section comprises an introduction to biochemistry and biology of nucleic acids. The structure and function of DNA are reviewed in R. Lavery's chapter. The next contribution, by V. Fritsch and E. Westhof, concentrates on the folding properties of RNA molecules. The cellular processes involving these molecules are reviewed by J. Kadonaga, with special emphasis on the regulation of transcription of DNA. These chapters do not require any preliminary knowledge in the field, except that of elementary biology and chemistry.

The second section covers the biophysics of DNA and RNA, starting with basics in polymer physics with the contribution by R. Khokhlov. Advances in the understandinf of electrophoresis, a technique of crucial importance in everyday molecular biology, are then exposed in T. Duke's contribution. Finally, a large space in devoted to the presentation of recent experimental and theoretical progresses in the field of single molecule studies. T. Strick's contribution presents a detailed description of the various micro-manipulation techniques, and review recent experiments on the interactions between DNA and proteins (helicases, topoisomerases, etc.). The theoretical modeling of single molecules is presented by J. Marko, with a special attention paid to the elastic and topological properties of DNA.

The third section presents provides an overview of the main computational approaches to integrate, analyze and simulate molecular and genetic networks. First J. van Helden introduces a series of statistical and computational methods allowing the identification of short nucleic fragments putatively involved in the regulation of gene expression from sets of promoter sequences controlling co-expressed genes. Next the chapter by Samsonova et al. connects the issue of transcriptional regulation with that of the control of cell differentiation and pattern formation during embyonic development. This contribution ties the issues of data integration, image processing and dynamical modeling, focusing on a series of mathematical approaches to model the dynamical behaviour of complex genetic regulatory networks. This contribution includes brief descriptions and references to successful applications of these approaches, including the work of B. Novak, one of the teachers of the school, on the dynamical modeling of cell cycle in different model organisms, from yeast to mammals.

To complete the different chapters of this volume, the material corresponding to additional seminars and lectures, as well as to the public lecture in Les Houches by D. Chatenay can be downloaded from the Summer School web page, at the url: http://w3houches.ujf-grenoble.fr/sessions_ete/ete-82/session-82.html.