The ends of linear eukaryotic chromosomes generally consist of tandem G-rich repeats (TTAGGGn in humans), which specifically recruit telomeric protein factors to form large nucleoprotein structures called telomeres. Telomeres protect the chromosome ends from being recognised as DNA breaks and thus are essential for maintaining genome integrity. Telomere dysfunction is strongly linked to cancers and aging diseases. My group studies how telomeric complexes form the protective telomere caps in mammalian cells. Such understanding would enable us to understand how telomeres protect the chromosome ends from DNA damage repair pathways and how disease mutations give rise to dysfunctional telomeres.
This PhD project will focus on biochemical, structural and functional analyses of large mammalian telomeric complexes. The successful candidate will have the opportunity to acquire experience in mammalian cell culture, biochemical reconstitution/isolation of telomeric complexes, biophysical analyses, cutting-edge structural biology (with a focus on cryoEM and cryoET) and genome editing in mammalian cells. The work will contribute to our understanding of how telomeres are structured and maintained and the molecular basis of telomere dysfunction in human diseases. The LMB has world-class facilities and provides a great working environment. Enquiries to discuss details of the project are highly encouraged.
References
Arnoult N & Karlseder J. (2015) Complex interactions between the DNA-damage response and mammalian telomeres. Nat. Struct. Mol. Biol. 22, 859-866.
Shay JW. (2016) Role of Telomeres and Telomerase in Aging and Cancer. Cancer Discov 6, 584-593.
de Lange T. (2018) Shelterin-Mediated Telomere Protection. Annu. Rev. Genet. 52, 223-247.
Hu H, van Roon AMM, Ghanim GE, Ahsan B, Oluwole AO, Peak-Chew SY, Robinson CV, Nguyen THD. (2023) Structural basis of telomeric nucleosome recognition by shelterin factor TRF1. Science Advances.