Cornelia de Lange Syndrome (CdLS) is a rare multi-system genetic disorder caused by mutations in the regulatory and structural components of the cohesin complex. Cohesin organizes chromatin by mediating sister chromatid cohesion during mitosis and loop extruding DNA in interphase. Chromosome instability is rarely observed in patients, implicating the organizational role of cohesin in interphase in the pathogenesis of the disorder. Indeed, most patients have mutations in NIPBL, which is required for cohesin loop extrusion activity, and widespread transcriptional changes have been identified across CdLS patient samples.
Using the lab’s single particle tracking technologies, I will characterize NIPBL dynamics in both wild type and disease conditions to unpack how CdLS mutations cause disease. In addition, I will develop technologies to probe protein dynamics at specific loci to understand the impact of CdLS mutations on gene expression. Ultimately, studying CdLS will be a foothold to understanding the role of cohesin in genome organization and transcriptional regulation.