Research Fellow - Bioinformatics – Extrachromosomal DNA and tumour evolution Scientist

About the role

We are seeking a collaborative and self‑motivated bioinformatician post‑doctoral fellow to work on extrachromosomal DNA (ecDNA) in a vibrant and highly collegiate environment. ecDNA are circular genomic structures that can drive ultra‑high copy number amplification and correlate with poor clinical outcomes, yet their evolution, detection, and targeting remain largely unclear. This project aims to analyse ecDNA evolution over time using single‑cell RNA/ATAC sequencing and to develop a ctDNA‑based approach for detecting and monitoring ecDNA to support biomarker and treatment development.

The project will leverage existing whole genome sequencing data from multi‑region matched primary and metastatic tumours from the TRACERx lung cancer evolution and PEACE research autopsy programmes and will be part of the eDyNAmiC Cancer Grand Challenge.

TRACERx is a UK‑wide lung cancer evolution programme which started in and has to date recruited over patients. It is the first longitudinal cancer genomics study that forms the first national UK consortium focused on deciphering cancer evolution over space and time. TRACERx involves multi‑region sequence analyses of lung cancers (+ exomes and whole genomes in over patients) from pre‑invasive through to primary and metastatic disease setting, in order to understand cancer evolutionary life histories with detailed clinical annotation.

The co‑primary end points of the study are to investigate the relationship between intratumour heterogeneity and clinical outcomes, and to determine the impact of cancer therapies on intratumour heterogeneity. TRACERx has enabled additional analyses in the areas of immunology, circulating biomarkers, cancer cachexia and body composition, radiomics and tumour microenvironment. Future plans include tumour metabolic imaging and mass spectrometry metabolomics.

TRACERx is supported by the excellent bioinformatics facilities already available in our Centre together with substantial investment in bioinformatics staff, data storage and computer processing power. TRACERx has been highly successful, as of sequencing data from more than patients have been fully analysed resulting in a flow of high‑impact publications, including manuscripts in Nature, Cell, Science and New England Journal of Medicine.

PEACE is a pan cancer national research autopsy programme in which post‑mortem sampling allows access to tissue from all sites of metastasis, and to date has recruited over patients and performed over autopsies. PEACE aims to investigate the biological processes underpinning metastatic disease, including genomic and metabolic drivers of tumour dissemination, and failure of the adaptive immune system. The combination of both TRACERx and PEACE with patient co‑recruitment has established an unprecedented resource of multi‑regional matched primary and metastatic tissue, and therefore facilitates tissue‑ and blood‑based analyses from diagnosis to death.

This is the first national autopsy programme at such scale with a consortium of high calibre scientists and clinicians focussed on various projects relevant to metastasis and drug resistance.

eDyNAmiC is an international team of scientists with close collaborations tackling the challenges posed by extrachromosomal DNA in cancer. Supported by Cancer Grand Challenges, a global initiative addressing key issues in cancer research, it is funded by CRUK and the NIH. The team focuses on understanding ecDNA biology and developing new strategies to target its mechanisms in cancer.

The position is fixed term for 2 years.

The successful applicant should have a proven track record of publications, have previous experience with genomics data analysis, be fluent in at least one of the following programming languages: C++, Python or R, and will have strong skills in the field of genomics and desirably one or more of the following: tumour biology, ctDNA/blood‑based biomarkers, evolutionary biology, statistics and mathematics.

In the Cover Letter please provide evidence of the essential and desirable criteria in the Person Specification part of the Job Description.

• 41 Days holiday (including 27 days annual leave 8 bank holiday and 6 closure days)
• Defined benefit career average revalued earnings pension scheme (CARE)
• Cycle to work scheme and season ticket loan
• On‑Site nursery
• On‑site gym
• Enhanced maternity, paternity and adoption pay
• Employee assistance programme:
  Staff Support Service
• Discounted medical insurance