ISC-PIF Guest Researcher //
Ivan Junier
PhD in statistical physics.
I am interested in the functioning of biological systems. I am currently investigating the interplay between chromosome structuring, genome organization and genetic regulation. My leitmotiv is to understand both the impact of this interplay onto the functioning of cells as well as the molecular mechanisms underlying its coordination. To this end, I use methods coming from statistical physics and information theory in order to extract useful information from -omic data (genomic, transcriptomic, proteomic,...). I have also developed chromosome models using condensed matter principles.
From a more general point of view, I am interested in the statistical description of small systems, especially those that are far from equilibrium. These are ubiquitous in biological systems.
NEW!! — PhD project on : Multi-scale modelling of the chromosome and design of regulatory networks in the cellular space
Institut des Systèmes Complexes Paris Île-de-France, UMR7656 CREA CNRS
57/59, rue Lhomond 75005 Paris, France
tel.: +33-(0)1-42.17.40.35
fax: +33-(0)1-45.35.79.21
Epigenomics Program
Genopole®, CNRS UPS3201
Tour Évry2, 10è étage, 523 Terrasses de l'Agora
91034 Evry France
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ivan.junier (at) iscpif.fr ivan.junier (at) epigenomique.genopole.fr |
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Master students
Thibaut Lepage : Numerical investigation of the condensation of bacterial chromosomes
Svilen Iskrov : Investigation of the topological structure of global genetic networks
Research
Genome organization/Transcriptional regulation/Chromosome structuring
Chromosome organization: condensed matter approach
The good operation of cells relies on coordination between chromosome structure and genetic regulation, which is yet to be understood. This can be seen in particular from the transcription machinery: in some eukaryotes and bacteria, transcription of highly active genes occurs within discrete foci called transcription factories, where RNA polymerases, transcription factors and their target genes co-localize.
The mechanisms underlying the formation of these foci, the resulting topological structure of the chromosome, and more generally the coordination of genetic expression of groups of functionally related genes remain to be elucidated. In collaboration with François Képès (Epigenomics program, Genopole®, Evry) and Olivier Martin (LPTMS, Orsay), we have been developing a thermodynamic framework based on a polymer description of DNA in which genes effectively interact through attractive forces in physical space. This simplified picture of the chromosome allows to investigate the self-organizing properties of DNA under specific types of interactions. For instance, within this framework the formation of transcription foci can be explained as a self-organizing process whereby the interacting genes and the non-interacting DNA form two phases that tend to separate. In this context, we use numerical simulations to explore the resulting possible structures of chromosomes in space, which remains an insurmountable analytical problem. We have unveiled a rich zoology of the topological ordering of DNA around the foci. We also have shown that regularities in the positions of the interacting genes make the spatial co-localization of multiple families of genes particularly efficient.
The mechanisms underlying the formation of these foci, the resulting topological structure of the chromosome, and more generally the coordination of genetic expression of groups of functionally related genes remain to be elucidated. In collaboration with François Képès (Epigenomics program, Genopole®, Evry) and Olivier Martin (LPTMS, Orsay), we have been developing a thermodynamic framework based on a polymer description of DNA in which genes effectively interact through attractive forces in physical space. This simplified picture of the chromosome allows to investigate the self-organizing properties of DNA under specific types of interactions. For instance, within this framework the formation of transcription foci can be explained as a self-organizing process whereby the interacting genes and the non-interacting DNA form two phases that tend to separate. In this context, we use numerical simulations to explore the resulting possible structures of chromosomes in space, which remains an insurmountable analytical problem. We have unveiled a rich zoology of the topological ordering of DNA around the foci. We also have shown that regularities in the positions of the interacting genes make the spatial co-localization of multiple families of genes particularly efficient.
Fig 1: Left: Transcription factories (green dots) in a eukaryotic nucleus. Right: Snapshots of numerical simulations of a chromatin model leading to the formation of transcription factories (red dots). Different topological ordering of the chromatin can result on the formation of the foci.
Genomic organization: revealing order in genomes
Fig 2: One-dimensional clustering tendency vs.
periodic tendency of functionally related genes.
One of my goal is to develop bioinformatic tools in order to unveil specific organizations of genomes, and hence, to further understand the functional role of genomic organization at the cellular scale. For instance, specific genomic organizations of co-regulated genes are known to facilitate the spatio-temporal coordination of transcriptional regulation.
However, highlighting regularities in genomes is not an easy task due to the complexity of biological systems but also due to our lack of knowledge about the genome itself.
Recently, in collaboration with Joan Hérisson (Epigenomcis Program, Genopole®, Evry) and François Képès, we have developed a tool that is able to reveal short periodic complex patterns, which is robust with respect to the presence of both false information and biological noise.
As an application, we unveiled different strategies that are used by the model organism Escherichia coli in order to place functionally related genes along its chromosome. Interestingly, most groups of functionally related genes either tend to cluster one-dimensionally along the DNA or to be periodically organized. This suggests that a specific large-scale structure of the chromosome is used in order to coordinate the functioning of several cellular functions.
Work fluctuations in small systems
Out-of equilibrium work fluctuations have been shown to provide valuable information about the equilibrium properties of small systems. In particular, fluctuation theorems have led to new experimental tools, which are based on single molecule experiments. These are useful in order to explore in detail the thermodynamic properties of complex biomolecules such as proteins and nucleic acids. Using elaborate fluctuation relations, I have participated to the development of experimental protocols that allow to work out free energies (and hence stability properties) of intermediate states.
I am also interested on how to use fluctuations in an optimal way in order to experimentally explore energy landscapes of molecules.
Recently, in collaboration with Leonardo Trujillo (IVIC, Caracas, Venezuela) I have also been interested on the outcome of these fluctuation relations in athermal systems such as vibrated granular systems.
Fig 3: Recovering of free energy branches in single molecule experiments. Phys. Rev. Lett., 102, 070602 (2009)
Active collaboration
Biology:- François Képés (Epigenomics Program, Genopole®, Evry, Fr)
- Laurent Jannière (INRA, Jouy-en-Josas, Fr)
- Olivier Espéli, Frédéric Boccart (CGM, Gyf/Yvette, Fr)
Statistical Physics:
- Olivier Martin (LPTMS, Orsay, Fr)
- Felix Ritort (Univ. Barcelona, Sp)
- Leonardo Trujillo (IVIC, Venezuela)
In preparation
-- I. Junier, S. Iskrov, J-B. Rouquier, L. Jannière, F. Képès, Genome organization in the bacterial world.
-- L. Trujillo, I. Junier, A. Sarmiento, B. Berche, S. Luding, Work distribution invariants in a system of vibro-fluidized inelastically colliding particles.
-- I. Junier, Work fluctuations: using daemons to efficiently explore thermodynamic properties of small systems.
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Publications
Related to Biology
-- I. Junier, J. Hérisson and F. Képès, Genomic organization of cofunctional genes in bacteria: limits and strategies, submitted. (PDF on request)
-- I. Junier, J. Hérisson and F. Képès, Periodic pattern detection in sparse Boolean sequences, Algorithms for Molecular Biology, 5:31 (2010). PDF
-- I. Junier, O. Martin and F. Képès, Spatial and topological organization of DNA chains induced by gene co-localization, PLoS Comput. Biol., 6(2): e1000678 (2010) PDF
— I. Junier, A. Mossa, M. Manosas and F. Ritort, Recovery of free energy branches in single molecule experiments, Phys. Rev. Lett., 102, 070602 (2009) PDF
— M. Manceny, M. Aiguier, P. Le Gall, I. Junier, J. Hérisson and F. Képès, Spatial Information and Boolean Genetic Regulatory Networks, BICoB, 5462, 270-281 (2009) PDF
— M. Manosas, I. Junier and F. Ritort, Force-induced misfolding in RNA, Phys. Rev. E, 78, 061925 (2008) PDF
-- I. Junier and F. Ritort, Unstructured intermediate states in single protein force experiments, Proteins: Structure, Function, and Bioinformatics, 71, 1145-1155 (2008) PDF
-- I. Junier and F. Ritort, Single-domain protein folding: a multi-faceted problem, AIP Conference Proceedings, 851, 70-95 (2006) PDF
Statistical Physics
-- I. Junier, Local-energy approach to the dynamic glass transition, Europhys. Lett., 75, 723-729 (2006). PDF
— I. Junier and E. Bertin, Dynamic phase diagram of the Number Partitioning Problem, Phys. Rev. E, 70, 066126 (1-15) (2004). PDF
— I. Junier and J. Kurchan, Microscopic realizations of the Trap Model, J. Phys. A: Math. Gen., 37, 3945-3965 (2004). PDF
-- I. Junier and J. Kurchan, Tailoring symmetry groups using external alternate fields, Europhys. Lett., 63, 674-680 (2003). PDF
In preparation
-- I. Junier, S. Iskrov, J-B. Rouquier, L. Jannière, F. Képès, Genome organization in the bacterial world.
-- L. Trujillo, I. Junier, A. Sarmiento, B. Berche, S. Luding, Work distribution invariants in a system of vibro-fluidized inelastically colliding particles.
-- I. Junier, Work fluctuations: using daemons to efficiently explore thermodynamic properties of small systems.
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