Research Overview
The research in our group is concerned with understanding the effects of radiation on human tissues. Radiotherapy is a major and effective regimen used in the treatment and management of cancer. When human tissues are exposed to radiation, whether naturally occurring (e.g. from radon gas) or from diagnostic and therapeutic exposures, the damaging effects are not inflicted uniformly. As radiation passes through matter, it deposits its energy in "tracks", each much finer than the dimensions of a cell.
Little is known about the biological effects of the individual tracks as they traverse different regions of the cell and our group has developed experimental strategies to address exactly this question. Information from these studies is needed to understand and predict the effects of low-dose radiation, relevant both to fractionated and targeted radiotherapy and to cancer risk from diagnostic, occupational and environmental exposures.
We are applying a number of novel experimental techniques developed specifically to study the effects of radiation tracks in inducing damage and initiating processes in critical constituents and compartments of the cell. These include microbeam techniques for studies on individual cells, designed to locate the sensitive targets and identify the molecular pathways involved in their responses.
We employ targeted irradiation approaches capable of resolving actions at the sub-micron level within cells or tissue samples. A particular interest is the effect of radiation type or 'quality' on biological response in relation to the underlying mechanisms of action. Much of our interest is in stress responses involving signalling pathways which transmit information within cells and from cell to cell. These can involve damaging reactive oxygen species ("free radicals") and lead to DNA damage and stimulation of DNA repair pathways. Many of these effects occur immediately after irradiation or can cause instability in the genome leading to delayed effects in subsequent generations.Using our targeted microbeam approaches we can visualise at the microscopic level the responses of cells to DNA damage. The use of our microirradiation techniques coupled with immunofluorescence imaging of foci induced in cell nuclei, involving, for example, H2AX, PARP and CDKN1A (p21), is giving information about the recruitment and activation of proteins involved in processing DNA damage.
Our recent research has discovered the importance of a "bystander effect" of radiation that transmits damage from cell to cell. The effect may be important in some types of therapy and in determining the risks of radiation exposure. A key and topical question is whether "bystander" processes increase the effects of low-dose exposures by amplifying the number of cells damaged, or whether they decrease the effect, either by killing, and therefore removing, cells that have been damaged, or by causing them to differentiate and thereby lose their potential to proliferate. Interactions between different cell types within tissues may be an important mediator of tissue response to radiation exposure.
