Grant: Project Grant

Each of our cells carries an identical genome, yet different cell types display unique gene expression programs which are essential to their creation and function. These unique programs are generated by the concerted action of epigenetic, transcriptional, and posttranscriptional gene regulatory mechanisms. Another recently emerging facet of gene regulation is the impact of 3D genome organization. The large-scale physical architecture of chromosomes and their positioning within the nuclear space is correlated with transcriptional activity in cultured cells, and defects in genome organization have also been implicated in aberrant developmental and diseased states. However, in vivo chromosome conformations and the mechanisms that control them are not well understood. We have discovered an unexpected heterogeneity in chromosome conformations across cells and cellular lineages during embryogenesis in the model organism C. elegans. The focus of this proposal is to elucidate the links between these variable conformations and the functional outputs of different cell types during embryonic development. We will use a combination of super-resolution imaging, genetics, and computational biology approaches. Embryogenesis provides an excellent natural set of dynamic conditions to investigate the relationship between genome structure and function as cells transit rapidly from pluripotent states through specification and differentiation. C. elegans is the ideal animal model to conduct this research because it is genetically tractable, its transparency enables advanced 3D imaging, and its fully mapped and stereotyped cell lineage gives us the unique opportunity to simultaneously measure genome structure and cell identity. This work will shed light on the fundamentally conserved process of genome organization in cellular phenotypes, which can improve our understanding of diseases stemming from genome disorganization.