Our research involves looking in to the process of radiation induced cluster DNA damage.
Peter O'Neill's research is looking in to the process of radiation induced cluster DNA damage. Ionising radiation may be considered as a two-edged sword since it can induce cancer and other adverse responses in normal tissue or alternatively it leads to cellular inactivation, of considerable importance in radiotherapy. The genetic material (DNA) in cells is an important target for ionising radiation as it damages the DNA. If the damage is not removed by proteins which can restore the correct genetic code, potentially harmful effects of radiation such as mutations in the genetic code may occur and lead to significant biological consequences, such as cancer or severe late effects to normal tissue. In radiation oncology it is important to kill tumour cells but minimise damage to normal tissue. An important feature of ionising radiation is its ability to cause clusters of damage sites very close to one another. These clusters are very difficult to correct for as the repair proteins do not easily recognise the damage.
The complexity of clustered damage is thought to be a major feature that determines the biological effectiveness of radiations of different quality. The research focuses on identification of the processes leading to DNA damage, the recognition and processing of DNA damage and to identify the critical lesions and repair pathways involved in the biological responses to ionizing the radiation.
The objective of the research is to understand how these clusters of damage, which are formed by ionising radiation in cells, detrimentally interfere with the maintenance of the genetic code. As a consequence the effects of human exposure to radiation may be detrimental to health or lead to tumour cell death, which is of relevance to radiation oncology.
Professor Peter O’Neill has been the course Director of the MSc in Radiation Biology and Deputy Director of the CRUK/MRC Oxford Institute for Radiation Oncology within the Department of Oncology since 2005.
Following post-doctoral positions first at the Max-Planck-Institut für Strahlenchemie in Mülheim, Germany, and then at the Institute of Cancer Research in Sutton, UK, he spent 23 years carrying out research at the MRC Radiation and Genome Stability Unit (formerly Radiobiology Unit) in Harwell, Oxfordshire. He came to Oxford to lead the DNA Damage Group in 2005.
He is Associate Editor of the International Journal of Radiation Biology and of Radiation Research and has over 200 peer-reviewed publications. He provides consultancy and advice to several international organisations including the European Space Agency, was recently President of the Radiation Research Society of USA, a member of the Lasers for Science (LSF) Facility Access Panel for the UK’s Science and Technology Facilities Council and serves on several international committees relating to radiation. He is a Fellow of the Royal Society of Chemistry and was awarded the Failla medal and the Weiss medal as an outstanding member of the scientific community in recognition of a history of significant contributions to radiation research.
Cunniffe, S., Walker, A, Stabler, R., O’Neill, P and Lomax, ME. Increased mutability and decreased repairability of a three lesion clustered DNA damaged site comprised of an AP site and bi-stranded 8-oxoG lesions. Int. J. Radiat. Biol 90, 468--479 (2014)
Karwowski, BT., Bellon, S, O’Neill, P., Lomax, ME., Cadet, J. Effects of (5'S)-5',8-cyclo-2'-deoxyadenosine on the base excision repair of oxidatively generated clustered DNA damage. A biochemical and theoretical study. Organic & Biomolecular Chemistry 12, 8671-8686 (2014)
Reynolds, P.; Cooper, S.; Lomax, M.; O'Neill, P. Disruption of PARP1 function inhibits base excision repair of a sub-set of DNA lesions. Nucleic Acids Res in press doi: 10.1093/nar/gkv250 (2015)
Mariotti, L.G., Abdelrazzak, A.B., Ottolenghi, A., O’Neill, P. and M. A. Hill, Stimulation of intercellular induction of apoptosis in transformed cells at very low doses of ionising radiation: spatial and temporal features. Radiat. Prot. Dosim. in press doi:10.1093/rpd/ncv176 (2015)