Cellular response to chromosomal aberrations

Elaborate mechanism are employed by each cell to faithfully propagate their genome and preserve a stable karyotype (constant number of chromosomes). In pathogenic situations however, loss or gains of chromosomes are often observed. These changes affect either a single chromosome (e.g. extra copy of chromosome 21 in Down syndrome) or a large number of chromosomes, which is frequently observed in cancer cells. Little is known about the impact of these chromosome gains or losses on cell physiology and how they promote the pathogenic state. In our laboratory we are using cutting-edge methodology to study the causes and consequences of karyotype changes.

Our Model System

To generate human cells carrying a single extra chromosome we use a technique called micronuclei mediated chromosome transfer (MMCT). To generate cells with extra copies of the whole sets of chromosomes (tetraploid cells) or with variable aneuploidy we treat the cells with drugs that interfere with cell division. Using state-of-the-art techniques including live cell imaging or flow cytometry we analyze how these cells propagate their abnormal genome. We also exploit genomics, transcriptomics and proteomics to determine the effects of the extra chromosomes on genome stability and protein homeostasis.