Vrije Universiteit Amsterdam

  • At the VU we develop methods for the quantitative study, in real time, of the 3D structure and dynamics of whole mitotic chromosomes extracted from healthy and diseased single cells.
  • We will determine the mechanical properties of healthy and ‘diseased’ chromosomes and try to follow for example in real time and with molecular resolution, the segregation of metaphase chromosomes.
  • Moreover, we will analyse the protein dynamics on ultra-fine anaphase DNA bridges (UFBs) that develop during chromosome separation.
  • The VU provides the management, dissemination and exploitation of CHROMAVISION to ensure strategic, financial and contractual management of the consortium and the day-to-day operational project management. Also we will enable external stakeholders to become aware of, learn from and implement project results. Finally, we will prepare for exploitation of IP protected project results

Processing of fragile-site UFBs by the PICH–BTRR machinery.

a: Immunofluorescence images of anaphase U2OS cells treated with aphidicolin and displaying UFBs coated with PICH (green), RPA (red), and BLM (blue). Scale bar, 1 μ m. b: Use of optical tweezers to model the recruitment of BLMSNAP, TRR (not labeled), and RPAStrawberry to a partial single- and double-stranded model of an fsUFB before (1) and after (3) decorating it with PICHGFP (2). c: Schematic representation of the naked ssDNA and dsDNA (0) and the DNA-bound proteins (1–3) presented in b (blue, BLM; white, TRR; red, RPA; green, PICH). The figure is taken from Sarlos et al. Nature Structure & Molecular Biology, 2018, 868–876 with permission.