Date : 26/03/2009

Laboratory
RNA dynamics and Biomolecular Systems Lab
Institut Curie
CNRS-UMR168
11 rue Pierre et Marie Curie
75005 Paris
Director : Jean-François Joanny

PhD Supervisor
Hervé Issambert
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 1 56 24 64 74

Subjects / Tools-Methodologies:
1 : RNA self-assembly prediction / RNA structure modeling and bioinformatics
2 : RNA self-assembly in vitro / Atomique force microscopy
3 : RNA self-assembly in vivo/ in situ fluorescent microscopy

Summary of lab's interests

Our research concerns the properties and evolution of biomolecular networks, from their local structures and dynamics, at molecular scales, to their more complex global organization, at cellular level. 1- At molecular scales, we explore the properties of small regulatory circuits as well as self-assembled physical networks primary based on RNAs and their interactions. We investigate the design principles of efficient RNA-based regulatory modules using synthetic biology approaches coupled to advanced RNA simulations. We also study the self-assembly properties of natural non coding RNAs, following our recent discovery that a small regulatory RNA of Escherichia coli does form long filaments as well as extended nanostructures, like many proteins do. 2- At cellular scales, we are interested in the properties of large biomolecular networks and their evolution under genomic duplication-divergence processes at the level of individual gene or whole genome duplications. We study in particular how duplication-divergence processes bring not only genetic novelty but also evolutionary constraints that restrict by construction the emerging properties of biomolecular networks.

Summary of project

"Finding RNA with self-assembly properties"
Natural RNAs, unlike many proteins, are not known to form extended supramolecular structures, despites their wide variety of cellular functions. This is all the more striking, as synthetic DNA and RNA forming large nanostructures have long been successfully designed. This PhD project aims at discovering likely RNA self-assembly candidates within natural RNA sequences from bacterial as well as eukaryotic genomes, following our recent finding that a small noncoding RNA of E. coli self-assembles into long filaments as well as extended nanostructures (see Fig.1). The first objective is to develop efficient bioinformatics tools adapted to take into account some key structural constaints which promote RNA self-assembly. Some general sequence and structural conditions have already been identified using advanced RNA folding and interaction modeling tools. The second task will be to search for likely RNA self-assembly candidates within natural RNA sequences from bacterial as well as eukaryotic genomes. Conservative estimates suggest that dozens if not hundreds other natural RNAs might also form RNA self-assemblies awaiting to be discovered. The third goal will be to test experimentally the self-assembly properties of the most interesting candidates, using atomic force microscopy (Fig.1) as well as in situ fluorescent microscopy whenever possible. Finally, we would like to investigate in some details the functional properties of a few verified RNA self-assembly candidates, such as the regulatory RNA shown in Fig.1.