Grant: CIHR Fellowship

The genetic information of living organisms is encoded within the DNA, a linear polymer specifically organized within each cell nucleus. The accessibility to this information is typically regulated by the way the DNA is locally folded. As a consequence of local DNA folding the overall nucleus structure is determined. Cancerous cells use the genetic information differently than normal cells (e.g. undergo unlimited divisions) and as a consequence their nuclear structure differs from healthy cells. This can be investigated for diagnostic purposes e.g. using microscopy. In this work Hodgkin's lymphoma (HL), a blood cancer, is investigated using novel fluorescent based high-resolution microscopy techniques in order to reach into so far unknown information hidden in the structural details of the nuclear DNA. Our preliminary experiments demonstrate that HL cell nuclei contain circular DNA-poor regions of unknown purpose and origin, rather absent from healthy lymphocytes. The purpose of this project is two-fold: (i) to investigate a link between the characteristic DNA-poor spaces and typical for cancer cells telomere alteration via investigation of the structure's content as well as (ii) to attempt to link these specific structural features to e.g. aggressive disease phenotype (incurable 20% among 1000 Canadians suffering from HL per year) via quantitative super-resolution microscopy investigation of DNA poor spaces in patients of different disease history. Finding a potential link between the detailed structure of cancer cell nuclei studied with high-resolution microscopy and the patients' cancer disease profile can be expected to improve the accuracy of diagnosis and prognosis leading to an increase in patients' survival rate.