The Hickson/Liu laboratory is based in the Center for Chromosome Stability (CCS) at the University of Copenhagen. The CCS was established in 2015 through a grant of 8.5 Mio Euro from the Danish National Research Foundation. The CCS’s mission is to understand how cells minimize damage that can generate chromosomal instability. The main focus is on regions of eukaryotic genomes that are intrinsically unstable, including chromosomal fragile sites and repeated DNA sequences (e.g. telomeres). The long-term aim is to understand how genome instability triggers age-associated disorders in humans, including cancer, neurodegeneration and impaired fertility.
Research related to the project
The Hickson/Liu laboratory will provide expertise in molecular/cell biology within the Chromavision consortium. We aim to develop the technology to attach molecular ‘handles’ to human chromosomes, permitting controlled manipulation of chromosome structure in-vitro. We are experimenting with both in-cell and in-vitro attachment of handles to defined regions of the chromosomes – principally the centromeres (where the mitotic spindle attaches to chromosomes) and telomeres (the ends of chromosome). These handles will be designed to permit attachment of magnetic spheres or other microspheres for subsequent controlled manipulation via the use of ‘tweezers’. In parallel, we are genetically manipulating human cells to make alterations that mimic those found in certain human diseases; in particular cancer and neurological conditions. This will allow us to define in detail the effects that disease mutations have on chromosome stability and function. Ultimately, we hope to use a cell-free system to reconstitute in-vitro key events that occur during the mitotic phase of the human cell cycle, such as the disjunction of the two sister chromatids that comprise a human chromosome.
Development of a system to attach a molecular ‘handle’ to the centromere of a human chromosome. A DAPI-stained human chromosome (red) that has a micro-bead attached specifically at the centromere – the constriction point of the chromosome where the mitotic spindle attaches.