Principal Investigator: Dr. Carlos Penedo

 

 

PhD POSITIONS AVAILABLE

 Verification and processing of damaged DNA substrates by the human DNA repair complex TFIIH

The 10 subunit transcription factor IIH (TFIIH) participates in transcription and Nucleotide Excision Repair (NER). Mutations in TFIIH subunits lead to the debilitating genetic conditions xeroderma pigmentosum and Trichothiodystrophy, characterised by elevated cancer rates or premature ageing. Although the TFIIH complex has been known for many years there are still many outstanding questions relating to its structural organisation and mechanism. For example, it is not yet understood how the two helicase subunits of TFIIH, XPB and XPD, cooperate to unwind DNA and sense DNA damage.
Recently, we have succeeded in generating large amounts of recombinant human TFIIH using an insect cell system, raising the exciting opportunity to characterise the structure and mechanism of the complex. This project will focus on the steps involved in detecting DNA damage, interaction with the damaged DNA and loading of the TFIIH complex. We will utilise fluorescent DNA substrates and a novel technique to fluorescently label TFIIH at one specific position, allowing the use of fluorescence and optical or magnetic tweezer techniques to be applied to the system.
Our main aim is to answer very fundamental questions about the dynamics and organization of the TFIIH complex, including the lifetime of each individual protein-protein interaction, their assembly sequence and how this relates to function and sensing of damage DNA. The project is interdisciplinary and merges components of molecular biology and biophysics. Through the course of these studies, the student will receive training in molecular biology, fluorescence labelling and purification, protein expression and microscopy techniques. Laboratory training in these areas provides an excellent pool of skills and knowledge to be well positioned for a future research career in industry or academia. You will join an enthusiastic and well funded group studying related topics in the area of nucleic acid:protein interactions. Our labs occupy new, purpose built research space in the Biomedical Sciences Research Complex at St Andrews, with access to excellent facilities. This project is a collaboration with the lab of Prof M. White (http://synergy.st-andrews.ac.uk/crispr/). If you are interested in applying please contact Dr. Carlos Penedo (jcp10 at st-andrews.ac.uk) or Prof Malcolm White (mfw2 at st-andrews.ac.uk). More details and the online application package can be found here