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Nanopore barcoding for detecting metastases in liquid biopsies

  • Full or part time
  • Application Deadline
    Friday, January 03, 2020
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Liquid biopsy is set to revolutionized the capacity to detect, assess and monitor the evolution of cancer. This technology has a central role to play in precision medicine and population screening approaches, but remains limited by sensitivity and specificity. It therefore represents an unmet technological and clinical need. Clinical requirements include i) diagnosis: cell free DNA as an integrated assessment of mutation burden across all potential tumour sites for early detection and precision medicine applications, ii) disease monitoring: assessment for increasing and changing patterns of circulating cell-free (ccf)DNA associated with onset of metastasis or disease evolution, iii) predictive: changing molecular targets to inform on treatment choice, and monitor drug resistance. However, current ccfDNA detection technologies rely on DNA amplification and, in turn, the detection of low-copy numbers is challenged by DNA-copying errors that occur during amplification, and the skew away from low copy variants.
Solid-state nanopores (SSNP) represent a promising, emerging tool for high-throughput and sensitive detection of biomolecules, owing to their intrinsic single-molecule detection capability, high durability and low cost. In this project we will focus on the integration of SSNP and DNA self-assembly to generate an amplification-free barcoding approach that associates each copy of target mutation in solution with a unique DNA nanostructure that can be detected by nanopore transit with single-copy resolution. This novel integration of solid state and molecular nanotechnologies will be applied to detect initiation of tumour growth (primary and relapse), detect cancer subtype, and possibly determine mutation profile in liquid biopsy by targeting ccfDNA.

This project is available as one of five PhD studentships with the Bragg Centre to tackle fundamental and applied problems to create new and improve existing materials. These will address fundamental and applied problems across design, characterisation, fabrication and modelling. The Centre comprises around 150 members from over ten Schools and has had continued investment in excellent facilities and infrastructure, including a new building opening in 2020, to ensure that our staff and students benefit from state-of-the-art, high quality equipment and laboratories. We are a founding partner of the Henry Royce Institute, the UK’s Institute for Advanced Materials.

Funding Notes

Funding is available from the Bragg Centre for Materials Research for 3.5 years and covers the cost of academic fees at the UK/EU rate (currently £4,500 per year for 2019/20) and provides a stipend at EPSRC rates (currently £15,009 per year for 2019/20).

How good is research at University of Leeds in Agriculture, Veterinary and Food Science?

FTE Category A staff submitted: 14.40

Research output data provided by the Research Excellence Framework (REF)

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