Groupe a 5 ans “Spatial regulation of genomes”
Institut Pasteur – CNRS UMR 3525
28 rue du Dr. Roux
75015 Paris
Group leader and PhD advisor: Romain Koszul
Phone: 33140613325
E-mail: romain.koszul@pasteur.fr
Organization of Synthetic Yeast Genomes after Induced Evolution
Keywords: synthetic biology, chromosome organization, minimal genomes, evolution, metabolic engineering
Tools: HiC, genome assembly, computational analysis, molecular biology, bioinformatics
Project
This PhD grant (3 years) is part of the Induced Evolution of Synthetic Yeast genome (IESY) project funded by the
ERA-net Synthetic Biology initiative. Our international consortium (UK, GE, USA and FR) builds on pioneering work
from the Saccharomyces cerevisiae 2.0 (Sc2.0) project (Dymond et al., Nature, 2012; Annaluru et al, Science, in
press). The Sc2.0 project has successfully developed tools to design synthetic chromosomes and has created highfitness eukaryotic cells driven by these fully synthetic chromosomes. A crucial engineered component of the Sc2.0
synthetic chromosomes is the system for Synthetic Chromosome Rearrangement and Modification by LoxPmediated evolution (SCRaMbLE). The SCRaMbLE system generates a combinatorial diversity of genome complexity,
with the capability of genome minimization and the ability to generate new biological functions through rapid
evolution of genome content, copy number and gene order. We aim at characterizing and analyzing the events
recovered after selection of strains presenting higher fitness for several phenotypes. The PhD student will analyze
the new 3D chromosome organization of the evolved synthetic strains, as well as their replication profiles during
and after the process. In light of the transcription regulation and genome structure, we aim at deciphering new
rules regarding genomic regulation. Interdisciplinary aspect of the project: The project is interdisciplinary by
bridging several fields, notably genomics, genetics, chromosome 3D analysis with emerging applications of
synthetic biology. Also, our strains should exhibit industrially relevant modifications, which will also bring
interesting perspectives to the study. Eventually, depending on the profile of the student, extensive modeling and
statistical analysis could be envisioned.
Lab’s interests
Our team uses a combination of high-throughput imaging, genomic analysis and genome assembly tools to analyze
the interplay between genomes organization, cell cycle, and the environment. Most of the projects involve
collaboration between geneticists, biophysicists and mathematicians, some in the lab and some through
collaborations. We are concomitantly developing physics based approaches aiming at improving genome analysis.
Our “synthetic” approaches consist in redesigning and reassembling large regions of yeast chromosomes to ask a
broad range of questions. We are members of the Sc2.0 consortium, which aims at re-synthesizing the entire yeast
genome with features of interest, and laureate of the EraSynBio call.
 Marbouty, Cournac, Marie-Nelly, Flot, Mozziconacci, Koszul “meta3C unveils the diversity of microorganisms
chromosome organization” submitted
 Marie-Nelly, Marbouty, Cournac, Fischer, Zimmer, Koszul, “ Identifying functional elements in yeasts using
genomewide contact maps", 2014, Bioinformatics, in press
 Annaluru, Muller, Mitchell, Ramalingam, Stracquadanio, Richardson, Dymond, Scheifele, Cooper, Cai, Zeller,
Agmon, Hadjithomas, Tullman, Caravelli, Cirelli, Guo, London, Yeluru, Murugan, Kandavelou, Yang, Martin, …
Koszul, Bader, Boeke and Chandrasegaran. “Total Synthesis of a Functional Designer Eukaryotic Chromosome.”,
2014, Science, Apr 4;344(6179):55-8
 Hespeels, Knapen, Laurent, Hanot-Mambres, Heuskin, Koszul& and Van Doninck&, “Gateway to genetic exchange?
DNA double strand breaks in the asexual bdelloid rotifer Adineta vaga submitted to desiccation”, 2014, Journal of
Evolutionary Biology, in press