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A DPhil project available with Skirmantas Kriaucionis, Chunxiao Song and Xin Lu, Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford

Laboratories

This project is a collaboration between three research groups. Prof Skirmantas Kriaucionis’ research group aims to elucidate the molecular function of DNA modifications in normal cells, leading to the understanding of how defective pathways contribute to neoplasia. The Song laboratory combines various chemical biology and genome technologies to develop novel tools to analyse the epigenome. The Lu laboratory investigates molecular mechanisms that control cellular plasticity and suppress tumour growth.

Project

Better outcomes of cancer treatment could be achieved by getting timely information about how a tumour is behaving when treatment is administered. Current monitoring is complicated by the limited availability of non-invasive instruments (e.g. MRI) or the difficulty of invasive methods to capture the tumour state. Recent progress has demonstrated that minimally invasive liquid biopsy-based technology can detect tumours. This is based on the observation that tumours contribute to non-cellular DNA, which is found in blood. One of the most promising ways to detect tumour DNA is using DNA methylation, which is typically highly abnormal in cancer. This project will expand utility of the DNA methylation usage for tumour monitoring, by discovering how the tumour state impacts DNA methylation patterns in non-cellular DNA.

Training

The student will be trained in:

  • using newly invented TAPS technique to detect DNA methylation
  • massively parallel sequencing
  • working with different model organisms
  • mass-spectrometry
  • genome engineering
  • understanding tumour biology
  • innovative treatments.

References

  • Cell-free DNA TAPS provides multimodal information for early cancer detection. Siejka-Zielińska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver EL, Bekkali N, Schuster-Böckler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song CX.
  • Distinct contributions of DNA methylation and histone acetylation to the genomic occupancy of transcription factors. Cusack M, King HW, Spingardi P, Kessler BM, Klose RJ, Kriaucionis S.
  • Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands. Owen RP, White MJ, Severson DT, Braden B, Bailey A, Goldin R, Wang LM, Ruiz-Puig C, Maynard ND, Green A, Piazza P, Buck D, Middleton MR, Ponting CP, Schuster-Böckler B, Lu X.