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Cancer Grand Challenge Studentship

Project: extrachromosomal DNA evolution in non-small cell lung cancer

  • Primary supervisor: Mariam Jamal-Hanjani
  • Secondary supervisor: Nnennaya Kanu

This is a 4-year PhD studentship funded by Cancer Research UK, which covers tuition fees at Home and Overseas rate and the PhD stipend £21,285.

Closing date: 18th November 2022 at 5pm GMT.

Extrachromosomal DNA (ecDNA) are circular genomic structures that are a feature of cancer cells. They are associated with aggressive tumour behaviour, implicated in target therapy resistance, promote ultra-high focal genomic copy number and have been shown to contribute to genetic heterogeneity through ecDNA asymmetric segregation and inheritance during mitosis. ecDNA often forms in micronuclei however the association between ecDNA release and ctDNA is unknown. Methods to extract and isolate ecDNA have not yet been utilised in longitudinal samples. The TRACERx and PEACE studies provide a unique opportunity to track ecDNA in non-small cell lung cancer through multi-regional sampling at diagnosis, relapse and autopsy. With longitudinal plasma sampling, it may also be possible to obtain evidence of ecDNA shedding through ctDNA detection methods.

This project will involve the longitudinal analysis of ecDNA evolution through CRISPR-CATCH, single cell RNA/ATAC-seq and ctDNA detection and will form part of the eDyNAmiC CRUK Grand Challenge. CRISPR-CATCH is a method developed by the Chang lab that utilises the differential migration of ecDNA and chromosomal fragments through pulse field gel electrophoresis following CRISPR targeted DNA cuts. Using this method, the fine sequence resolution of ecDNA can be elucidated in bulk tissue samples, facilitating the discovery of functionally specialised ecDNAs that contain oncogenes or regulatory elements such as super enhancers. Single cell RNA and ATAC sequencing provides an opportunity to understand the epigenetic and transcriptional consequences of ecDNA evolution to autopsy and the quantification of genetic, epigenetic, and transcriptional heterogeneity in samples where ecDNA is detected. 

Application Procedure

For more information and to apply, please download the following documents:

Shortlisting and notification will likely take place W/C 21st November 2022. Queries about the application procedure or recruitment process should be directed to: ci.scholarships@ucl.ac.uk