The spatial arrangement of chromatin in interphase nuclei is non-random and plays a fundamental role in genome function and stability in physiology and disease. Recent advances in spatial genomics techniques unveiled that the chromatin spatial arrangement varies substantially from cell to cell, even among cells of a functionally homogeneous population. The investigation of the interplay between non-randomness on the one hand and variability, on the other hand, is one of the main open questions in the genome structure field. The interest of our laboratory is to investigate this dichotomy by combining imaging techniques, genomic data, structural bioinformatics, and physical theories carrying out our studies in single nucleus resolution at nanoscale.

Spatial Genomics tools and modelling

The advance of spatial genomics techniques (such as sequential OligoSTORM) that enable the direct visualisation of multiple genomic loci in the nuclear space at single nuclei resolution will significantly advance our understanding of 3D genome function and regulation at single nuclei resolution. However, in addition to the direct visualisation of the 3D genome at varied scales and resolutions, there is a need for standardised quantitative analysis and modelling methods to achieve a more precise high genomic-resolution view of the chromatin folding at the single-cell level. To this end, our lab develops innovative computational tools and algorithms to shed light on the cell-specific genomic regulatory circuits and how their variation could enhance the communication within the nuclear space.

lncRNAs and 3D genome plasticity

Nuclear-retained RNAs have a role in governing chromatin organization, transcription, and the formation of different nuclear condensates. By using a theoretical modelling approach, we have computationally identified a particular class of nuclear-retained long non-coding RNAs (lncRNAs) that have the potential to interact directly with chromatin mediating the spatial segregation of active and inactive chromatin compartments. This organisation is important for maintaining the genes activation patterns that determine the cell-specific identity. During development, extensive 3D structural changes occur within the nuclear space at the transcriptome and the compartment level. Our group is interested in identifying the cell-identity-dependent structural signatures that characterise these processes and the role of lncRNAs in the rise of these structural signatures.