Targeting DNA repair to increase efficacy of radiotherapy
Radiotherapy eliminates cancer cells through induction of DNA damage. However, in some cases the cancer cells may be radioresistant due to their capability to repair the damage. Therefore, one way to increase the efficacy of radiotherapy is to inhibit DNA repair.
The aim of this project is to explore new promising combinations of radiotherapy and drugs that inhibit DNA repair. Our group has recently performed a flow cytometry based large-scale screen in cancer cell lines treated with radiation and drug libraries, where we have identified several candidate drugs inhibiting DNA repair. The student will validate the effect of one or more of these drugs, and investigate whether the reduced repair capacity is associated with reduced survival. Furthermore, the student will explore the mechanistic details of how these drugs work to inhibit DNA repair. Such knowledge about drug/radiation combinations is important in order to make good treatment decisions in the future, as different cancers may respond to treatment in different ways. A long term goal is to also investigate whether the new combination of drug and radiotherapy will alter anti-tumor immune effects. This student project is connected to a larger ongoing project in our group supported by the Norwegian Cancer Society entitled "Targeting DNA repair to improve radiotherapy and immune effects".
Methods:
The student will use various methods to explore DNA-damage signaling and cell death in irradiated cancer cell lines. Among these methods are: cell culture techniques; DNA-damage induction by the use of an X-ray machine; multiparameter flow cytometry, western blotting and immunofluorescence microscopy to detect signaling events; and clonogenic survival and metabolic assays to study cell viability.
Qualifications:
We seek a highly motivated and dedicated student with interest in molecular cancer research.
Supervisors:
Main supervisor:
Group Leader Randi G. Sylju?sen
22781468; randi.syljuasen@rr-research.no
Co-supervisor:
Postdoc Sissel Hauge
22781459; sissel.hauge@rr-research.no
Research Group:
Radiation Biology and DNA damage signaling
Department of Radiation Biology
Institute for Cancer Research
Norwegian Radium Hospital
Oslo University Hospital
Ullernchausseen 70
0379 Oslo