About the Project
This is a 4-year CASE studentship funded by BBSRC and AstraZeneca, which covers tuition fees at Home UK rate and a stipend of £21,285 per annum.
Extrachromosomal circular DNAs (ecDNAs) are circular structures containing oncogenes and regulatory elements that occur in 20-50% of cancers, but are rarely found in normal cells. Specifically, genome sequencing and cytogenetic analyses have identified the presence of known oncogenes, such as EGFR, MYC, cyclin D1, CDK4 together with promoters, enhancers and regulatory regions on these amplicons. The molecular biogenesis of ecDNA has to date been poorly explored, however genome instability and DNA repair mechanisms have been implicated. Lung TRACERx, a study employing multi-region genome sequencing to determine the timing of somatic events in relation to distinct genomic instability processes has confirmed that a high proportion of the lung cancer genome present ecDNA. The objective of this PhD project is to study how mutations in different epigenetic regulators, DNA damage repair and aberrant mitotic events can shape the chromosomal copy number landscape, causing recurrent aberrations and impacting the generation of ecDNA during tumour evolution. Ultimately, elucidation of the mechanisms of formation, maintenance and regulation of ecDNA in lung cancer would shed insight on its contribution to oncogenesis and response to targeted therapeutics.
The student will use cutting edge technologies ranging from genome editing by CRISPR and drug screening with lung cancer clinical inhibitors, lung cancer cell lines and cells derived from TRACERx tumours. A range of technologies will be used and developed to assay the genesis of ecDNA.
This project is a collaboration between Dr Nnenna Kanu in the team of Prof Charles Swanton’s at the UCL Cancer Institute and Oncology Bioscience in AstraZeneca. The Ph.D. student will be based at the UCL Cancer Institute, London. The student will have the opportunity to work within both the global PhD and post-doctoral student communities in UCL and AstraZeneca.More detailed information about the research project is available on request from [Email Address Removed]
- Minimum upper second class Honours Degree in natural sciences, biomedical science and engineering, tissue engineering or related discipline, or an overseas qualification of an equivalent standard.
- Knowledge of molecular biology is required for this project.
- Preliminary knowledge of research techniques.
- Evidence of motivation for and understanding of the proposed area of study.
- Ability to develop understanding of complex problems and apply in-depth knowledge to address them.
- Potential to develop expertise in new areas of the subject.
- Potential for innovation and initiative, and evidence of an ability to work independently.
- Effective communication skills in both written and spoken English.
- Relevant laboratory research experience.
- Experience of cell culture, NGS and CRISPR laboratory techniques.
- Experience in immunofluerescence-based assay.
Duties and responsibilities
- To apply highly specialist scientific skills and expertise to lead in the delivery of high- quality research and the preparation of high-impact research publications.
- To keep abreast of current developments in this research area.
- To report research progress to the supervisory team, the Cancer Institute, and at scientific conferences and meetings.
- To work with other scientists within the Song, and Mittnacht teams as necessary.
- To work safely by adhering to all University policies and practices, including preparing and following laboratory risk assessments, and complying with Health and Safety policies, ethical approval processes and Human Tissue Act guidelines.
Analytical and Judgement Skills
- To demonstrate high-level of technical and analytical skill to resolve complex problems, requiring analysis, interpretation and expert judgement to find the most appropriate solutions.
- To identify, interpret and integrate information from a wide variety of sources, and critically evaluate the quality and assumptions of these data.
- To show initiative and the ability to make decisions in areas where no previous work has been undertaken.
- To show awareness of your own developmental needs and undertake appropriate training where appropriate.
- To comply with professional codes of conduct.
The UCL Cancer Institute is dedicated to consolidate cancer research at UCL and to promote links with our partner teaching hospitals, in order to support excellence in basic and translational cancer studies. The Institute draws together talented scientists working together to translate research discoveries into developing better, more effective therapies for cancer patients. It holds Cancer Research UK and Experimental Cancer Medicine Centre of excellence status, housing approximately 580 staff, including 120 PhD and MD (Res) students, and 40 MSc students. Research is supported through state-of-the-art platform facilities including the Genomics Facility supporting next generation sequencing, including single cell resolved technologies; a dedicated bioinformatics unit; the Proteomics Facility, Imaging and Cell Sorting (supporting automated, confocal and time-lapsed microscopy, MoFlo and Flow Cytometrie); the Pathology Suite (supporting laser capture microdissection, tissue arrays and immune-histology services), the Experimental Imaging unit and Transgenesis services.
AstraZeneca is an exciting global, innovation-driven biopharmaceutical company. We’re inspired by what science can do. Driven by the desire to meet unmet patient needs in our core therapeutic areas. Bold in our thinking. Proactive in pursuing discoveries.
At sites across the world, we bring teams together in a spirit of collaboration to turn great ideas into life-changing medicines – strengthening our product portfolio and harnessing the potential of a pipeline across all stages of the drug development process.
So, if you share our focus and passion, join us and make a difference to patients – and in return, we’ll help you develop way beyond what you thought possible.
Further details and application process
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