Informace o projektu
Visualizing how chromosome-end architecture preserves genome stability (ENDVISION)

Telomeres safeguard chromosome ends and are essential for genome stability and cancer suppression. Their maintenance is orchestrated by the shelterin complex, which must simultaneously protect telomeres from DNA damage responses and regulate access for telomerase. However, how shelterin balances these opposing functions through its spatial organization along telomeric chromatin remains entirely unknown – a critical gap in telomere biology and cancer research, as dysregulation of telomere maintenance is a universal driver of tumorigenesis. ENDVISION directly tackles this problem by integrating targeted genome editing, super-resolution microscopy, and cellular cryo-electron tomography to visualize shelterin organization and telomeric chromatin architecture in intact human cancer cells. This interdisciplinary strategy will generate the first multiscale structural model of human telomeres, revealing telomere-specific vulnerabilities exploitable for first-in-class cancer therapeutics, while establishing a broadly applicable framework for studying chromatin–protein complexes in their native environment. I am uniquely positioned to lead ENDVISION: I have generated the required endogenously tagged cancer cell lines, developed single-molecule imaging platforms, and published field-defining contributions to telomere biology. Moreover, I have built a strong international network of collaborations across Europe and the United States, strengthening the capabilities essential to the project’s success. Therefore, ENDVISION builds directly on my expertise and will establish a high-impact research program at the Faculty of Science, Masaryk University. This environment will position my group for competitive international funding, including an ERC Starting Grant.