PHASE-CHROM was awarded the BIST Ignite Grant in March 2018.
Intracellular phase segregation is emerging as a common biophysical basis underlying many important cellular functions. However, demonstrating its existence in the full complexity of the cell is challenged by the spatiotemporal scales involved, and the labile nature of the molecular interactions involved in these liquid-like compartments. The overarching goal of PHASE-CHROM is to reveal the existence of phase segregation induced by poly ADP-Ribose (PAR) in the cell nucleus, and to determine its role in chromatin organization, nuclear ATP synthesis, and ultimately gene expression in breast cancer cells. By joining forces between two different institutes at BIST, we will merge molecular & cell biology techniques with cutting-edge optical nanoscopy, single molecule dynamic approaches and theoretical biophysics into a unique multidisciplinary approach that will deliver first experimental evidence of PAR-dependent liquid demixing in the context of gene expression in the nucleus of living cells.
Multidisciplinarity within PHASE-CHROM
To investigate the role of phase separation in gene regulation it is imperative to take an integrative and multidisciplinary approach. We are facing questions derived from genomic, biochemical and conventional live microscopy data that cannot be pushed forward without studying their organization at the relevant spatial and temporal scales, and how they are affected by PAR and nuclear ATP synthesis inhibition. The two main postdoctoral researchers involved in the project are already actively collaborating in the generation of plasmids and cell lines for the study, and designing strategies for the challenging single molecule experiments to be performed at ICFO. Moreover, for the mathematical modelling of particles, researchers from the ALBA Synchrotron will collaborate in PHASE-CHROM, further driving the level of multidisciplinarity of the project.