Doctoral degree for Niek van Wietmarschen
After 4 years of research at the Laboratory of Genetic Instability and Ageing, Niek van Wietmarschen successfully defended his dissertation on November 30, thus earning the title of Doctor. The dissertation, titled “Genome instability, Lessons from single-cell sequencing studies”, can be summarized as follows:
Bloom syndrome (BS) is a genetic disorder caused by mutations in the BLM gene, which encodes for a protein with multiple functions in DNA repair. Symptoms include sensitivity to sunlight and cancer development at an early age. The average life expectancy is 26 years and cancer is frequently the cause of death. Cells derived from persons with BS show a rapid accumulation of mutations, including a type of structural mutation called a ‘sister chromatid exchange’, or SCE. It is believed that elevated SCE frequencies play a role in the development of cancer, but the exact mechanisms behind this hallmark feature of BS cells is not fully understood.
We developed a new technique called Strand-seq that allows us to detect different types of changes in the structure of chromosomes, including SCEs, at higher resolution than previously possible. For this thesis, we investigated the elevated SCE frequency seen in BS cells. We show that these SCEs occur spontaneously and are not induced by experimental factors, as was previously suggested. We also show that SCEs in BS cells frequently occur at structures in the DNA called G-quadruplexes, especially when these structures form in active genes. Finally, we developed another application for Strand-seq allowing us to detect types of mutation associated with loss of variation between chromosomes, which is believed to contribute to cancer development in persons with BS. Our hope is that this research will one day contribute to the development of a treatment for Bloom syndrome.
Congratulations Niek, with this wonderful accomplishment, and good luck with the next step in your academic career!