The main interest of our lab is to study the effect of external physical cues on cell nuclear organization in space and time. We aim to investigate, relaying on quantitative and multidisciplinary approaches, if and how in function of specific mechanical stress genes are re-positioned and/or differentially activated.
We want also identify which are the biological consequences of those possible rearrangements with a particular focus on tumor transformation.
First effort of the lab will be to design a statistical three-dimensional map of absolute chromosomes positioning. Combining chromosome painting and micro-patterning, a technique used to impose to cells predetermined shapes, will allow to visualize the Chromosome Territories (CT) organization in single cells with fixed geometry.
Successively, all single cell data could be superimposed and averaged to obtain a mean map of CT absolute positions relative to the geometry imposed to the cell population. We expect that the normalization of the cell shape obtained with micro-patterning would reduce the variability previously reported in CT positioning. We will possibly identify regions made of single or set of chromosomes, with higher or lower variability in their absolute positioning.
Will we find the chromosomes radially distributed around an axis of symmetry coinciding with the axis of polarity? Furthermore, how will changing the shape of micro-patterns affect the CT mean map? And which are the molecular players responsible of this interaction? And which phenotypes will be triggered by the silencing of each of them? Finally, how different is the CT arrangement between parental and tumor cells at different stages of transformation?