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The primary aim of my work involves studying chromosome positioning in the interphase nucleus of cancer cells. Various studies have shown that chromosomes occupy specific territories in the nucleus. The gene-dense chromosome 19 territory is located close to the center of the nucleus, whereas the gene-poor chromosome 18 territory is peripheral in position. Interestingly this pattern is conserved in evolution. The factors involved in specifying the position of chromosomes in the nucleus are rather unclear. It is also intriguing to understand how aneuploidy – a hallmark of many cancer cells, influences chromosome positioning. My goal is to compare chromosome territories of different cancer cell lines with a specific aim of observing the territories of aneuploid chromosomes. This is being studied by 3 dimensional- Fluorescence In situ Hybridization (3D-FISH), where chromosomes in the nucleus are hybridized using chromosome painting probes, without much perturbation of the nuclear morphology and are visualized using confocal microscopy.
The fundamental question of how chromosome territories are organized in cells with genomic instability can be ably complemented by analyzing transformed mouse cell lines since various genetic events are known to cause chromosomal aberrations in such cells. A combination of approaches involving analysis of a) cancer cell lines b) mice with mutations in genes leading to genome instability in conjunction with imaging methods will hopefully help us unravel some of the underlying mechanisms that regulate or deregulate higher order chromosome dynamics in cancer cells.