PhD student in DNA repair

Nucleotide Excision Repair (NER) is a versatile and important DNA repair pathway that protects against cancer and aging by removing different types of helix-distorting DNA damage. TFIIH is a dual-function transcription/DNA repair complex that plays a central role in NER, by opening of the DNA helix and verifying the presence of DNA damage, and in transcription, by helping RNA polymerase II initiate RNA synthesis. Intriguingly, hereditary defects in TFIIH are associated with several distinct, clinically heterogeneous diseases characterized by cancer predisposition, progressive neurological defects, developmental failure and segmental progeria, whose pathogenesis is not fully understood. As NER protects against cancer and aging, studying TFIIH function is crucial to better understand human health.

In this project, the PhD candidate will investigate the biological impact, and underlying mechanism, of TFIIH mutations, as well as the role and activity of novel identified proteins that regulate TFIIH and NER function. To this end, a multidisciplinary approach will be employed, with molecular, genetics and cell biological techniques ranging from various DNA repair assays, CRISPR-Cas9 gene editing, and live confocal imaging to quantitative proteomics and transcriptomics. Furthermore, both human cells and C. elegans will be used as model systems.