DNA Sequence context plays an important role in the rate at which Nucleic Excision Repair (NER) is able to excise lesions. Small changes in both nearest and further neighbouring bases has been studied, however, the interactions between DNA-carcinogens and these base contexts is largely unknown. There are at least sixty carcinogens present in tobacco smoke many of which are thought to cause cancer by the induction of DNA damage. This damage is often caused by the covalent bonding of tobacco carcinogens, including Nicotine-derived nitrosamine ketone (NNK) derived carcinogens, to DNA bases. The local DNA sequence context and methylation status of the sequence impacts upon the carcinogen binding frequency, the level of damage, the rate of repair and therefore subsequent mutation pattern, or signature.
Project Aims
Use Molecular Modelling techniques, such as dynamics, multivariate analysis and docking, NNK derived carcinogens (e.g. O6-[4-oxo-4-(3-pyridyl)butyl]guanine (O6-pobG)) on cancer hotspots in DNA as well as how the differing levels of distortion in the DNA sequence may affect its ability to bind to DNA repair machinery.
Project objectives
• Create parameters to run NNK adduct simulations using the GROMACS software
• Run molecular dynamic simulations on a number of DNA cancer hotspots and control sequences
• Dock the resulting structures into a DNA damage sensor protein (e.g. the Rad4/XPC complex)
*Please note this project can be completed as a PhD or MPhil*
Candidate requirements
A 1st or Upper 2nd class UK honours degree or equivalent. Please visit School of Biosciences Postgraduate Research for more details.
For those whose first language is not English, IELTS with an overall score of 6.5 with 5.5 in all subskills, or equivalent. Please see our English Language Requirements guidance for more details.
How to Apply
To submit a formal application via Cardiff University’s online application service, click the 'Institution Website' button on this advert; in the ‘Apply’ box at the top-right of the page, select Qualification (Doctor of Philosophy/Master of Philosophy), Mode of Study (Full Time) and Start Date (this can be flexible as it is a self-funded project). This will take you to the application portal.
Candidates must submit the following:
• Supporting statement
• CV
• Qualification certificates
• Proof of English language (if applicable)
In the research proposal section of the application, specify the project title and supervisors of the project. In the funding section, specify that you will be self-funding. If you are applying for more than one Cardiff University project with the same entry intake, please note this in the research proposal section as the form only allows you to enter one title.
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