Telomeres safeguard chromosome ends and are essential for genome stability. Their maintenance is controlled by the shelterin complex, which protects telomeres from DNA damage responses while regulating telomerase access. However, how shelterin achieves this balance through its spatial organization and interactions with telomeric chromatin remains unknown – a critical gap in cancer biology, since impaired telomere maintenance is a hallmark of tumorigenesis. TeloScope will uncover how shelterin proteins are organized along telomeric chromatin and resolve their macromolecular structures directly in human cancer cells. Building on my recently generated endogenously HaloTagged shelterin cell lines, I will combine super-resolution (SR) microscopy to map shelterin distribution with nanoscale precision and cellular cryo-electron tomography (cryo-ET) to visualize telomeric chromatin ultrastructure at shelterin binding sites. This correlative strategy will generate the first multiscale model of shelterin–telomere interactions, providing a molecular mechanism for how shelterin coordinates telomere protection and elongation. The findings will reveal telomere-specific vulnerabilities exploitable for first-in-class cancer therapeutics and establish a broadly applicable framework for studying chromatin-associated protein complexes in their native context. The project aligns with the EU Health Cluster, Mission on Cancer, and Europe’s Beating Cancer Plan, reinforcing Europe’s mission-driven research agenda. Hosted at Masaryk University, Czechia, in the lab of Prof. Jiří Fajkus, a world-leading expert in telomere biology and chromatin structure, I will receive training in SR microscopy, cryo-ET, and career development. A research stay in Dr. Kelly Nguyen lab (MRC Laboratory of Molecular Biology, UK) will provide expertise in telomeric structural biology and strengthen international collaborations – laying the foundation for my transition to research independence in Europe.

Cíle udržitelného rozvoje

Masarykova univerzita se hlásí k cílům udržitelného rozvoje OSN, jejichž záměrem je do roku 2030 zlepšit podmínky a kvalitu života na naší planetě.