The SynarchiC project aimed at tackling questions related to the functional organization of bacterial and eukaryotic genome during the cell cycle. We exploited a variety of species (Escherichia coli, Saccharomyces cerevisiae) to investigate various aspects of chromosome 3D folding regulation, and interplay with a number of DNA metabolic processes. The work involved designing new experimental approaches involving synthetic and artificial chromosomes to address these questions. Overall, the different tasks have been completed, and for some of them led to unexpected directions, including exploration of similar questions in the underexplored domain of life archaea, or the exploitation of deep learning for genomics to explore the interplay between sequence composition and chromatin activity. The Synarchic project was organized into three main work packages, that each have led to new discoveries on our understanding of the regulation of genome folding in a variety of organisms.
Our study of how transcription affects the folding and dynamics of the Escherichia coli chromosome, published in Nature Structural & Molecular Biology (Bignaud et al., 2024), demonstrated that the activation of a single transcription pathway in a silent genome creates significant topological constraints, influencing the organisation of the entire genome. This work is following another study on the regulation of sister chromatids intermingling following replication in this species (Conin et al., 2021). In addition, our research into the role of chromosome structural maintenance complexes (SMCs) and transcription in bacterial and archaeal chromosome folding, published in Molecular Cell (Cockram et al., 2020; Yáñez-Cuna et al., 2023), has highlighted the universal nature of these regulatory mechanisms in all areas of life. We have also studied the way in which sequence composition dictates chromatin structure and function (Meneu et al. 2025), showing that DNA introduced into a new nuclear environment is processed on the basis of host sequence rules. In addition, our research into the regulation of eukaryotic chromosome 3D folding by the cohesin complex in S. cerevisiae during replication has been documented in several publications (Dauban et al., Molecular Cell, 2020 ; Bastié et al., Nature SMB, 2022 ; Garcia-Luiz et al., Nature SMB, 2019 ; Elife, 2022 ; Bastié et al., Molecular Cell, 2024). In bacterial cell cycles, we found that inactivation of Topo IV leads to significant chromosome reorganisation, with distinct roles played by Topo III, MatP and MukB in sister chromatid segregation. Finally, our exploration of genome folding in the eukaryotic amoeba Acanthamoeba castellanii during infection with Legionella pneumophila involved the development of new computational methods and the assembly of complete genomes of reference strains, revealing infection-dependent chromatin reorganisation (Matthey-Doret et al., Genome Research, 2022). Our efforts have also led to the creation of several open access programmes associated with these publications.
These works, and others, were presented at international conferences and research centers. The funding has also been instrumental in developing new technologies and computational tools, which have been essential for our research. Altogether, they represent significant advancements made in understanding chromosome dynamics, with the ERC grant enabling us to expand these approaches to new biological questions, forming the basis for our future research.
