Stress-inducible transcription factors in the UVA dose rate effect observed in human skin cells
Supervisor: Dr Sarah Allinson
Environmental exposure to ultraviolet radiation (UV), mostly derived from sunlight, is the major risk factor for skin cancer. Cancers of the skin are the most commonly occurring malignancies in the Caucasian population and represent a significant burden on both individual quality-of-life and societal resources. Until recently it was assumed that longer wavelength UVA radiation was relatively unimportant in terms of the cancer-causing effects of sun exposure. However, it is now understood that in reality UVA makes a significant contribution to skin carcinogenesis. Moreover, the biological effects of UVA exposure have several unique features compared to those for shorter wavelengths of UV. One such feature is the UVA inverse dose rate effect whereby UVA delivered at a lower dose rate (i.e. intensity) is more harmful to cells than UVA delivered at a higher dose rate for the same total dose. This recently discovered phenomenon has clear implications for the assessment of the public health risks of UVA exposure but its molecular basis remains little understood.
The aim of the project will be to characterise the involvement of stress-inducible transcription factors in mediating the dose rate effect. The results will provide further information about the process of UVA carcinogenesis and potentially unveil new biomarkers for the harmful effects of UVA exposure. The project will provide postgraduate training in a range of cellular and molecular techniques including cell culture and irradiation; Western blotting; RT-PCR; immunoprecipitation; reporter gene assays and electrophoretic mobility shift assays.