Exploiting Clonal Cell Variation to Identify Novel Targets to Enhance the Effects of Radiation in Cancer Therapy
Although significant breakthroughs have been made in developing new cancer treatments, the overall impact in many disease types such as lung and pancreatic cancers, has been modest. Recent studies have recognised the inherent clonal variability of cancer cell populations within patients and also in experimental models, including common cell lines grown in culture. A recent study (Ben-David et al., Nature v560, pp325–330 (2018)) has demonstrated that this variability can be exploited to identify signalling pathways associated with sensitivity to targeted therapies. In this project, clonal cell populations from multiple human lung cancer cell lines will be isolated and characterised for differential sensitivity to ionising radiation. Multiple single-clone molecular analyses (e.g. RNASeq, whole exome sequencing, CNA and cytogenetics) will be carried out to identify mutations and signalling pathways associated with radiation sensitivity, and thereby identify potential novel targets for future drug development. Target validation studies will include the generation of CrispR knockout cell lines and analysis of primary human cancer samples. Utilising the expertise across the Department of Oncology, this project offers broad training in cell and molecular biology, including target validation, drug screening and high-content microscopy, and would particularly suit students with strong interests in drug development and bioinformatics.