Diagnosing breast cancer with DNA entrapment and nanopore detection

Supervisor(s)

Dr James L Thorne and Dr Matteo Castronovo. Please contact Dr James L Thorne to discuss this project further informally.

Project description

Diagnosis of primary and metastatic breast cancer by liquid biopsy remains limited by sensitivity and specificity, and represents an unmet technological and clinical need. For primary tumour diagnosis, subtype classification and mutation profiling requires an invasive needle tissue biopsy, followed by diagnosis through histopathology and subtype classification by immunohistochemistry. Limitations of this procedure unavoidably impact the quality of clinical care in this process. For example, genetic testing (e.g. for BRCA1) of primary tumours may delay surgery, and biopsy is rarely (bone) or never (brain) performed for metastatic cancer so the metastasis is typically assumed (sometimes erroneously) to be the same subtype as the primary disease.

The goal of this PhD project is to develop a new type of cancer detection system, based on detecting circulating DNA that has been shed from a primary tumour or a newly growing metastasis using an origami capture system combined with nanopore DNA sensing technology. Crucially, the proposed technology would allow accurate and rapid profiling of a variety of BCa traits (subtype, genetic aberrations, burden), and offer a tool to assess metastatic cancer that is currently rarely (bone) or never (brain) performed.

If successful, this novel tool will detect somatic genetic abberations at unprecedented specificity and with state-of-the-art sensitivity, with lower cost implications for the NHS. In contrast, competing technologies in development (including liquid biopsy PCR, NGS and microarray based techniques) rely on DNA amplification and, in turn, the detection of low-copy numbers is challenged by DNA-copying errors that occur during PCR amplification, and skew away from low copy variants.

You will work with physicists, clinicians and molecular biologists to develop the new technology and compare specificity and sensitivity with competing techniques.

Key benefits

Be part of a welcoming multi-national research environment and receive multi-discipline training in DNA manipulation, clinical sample handling, in a state-of-the-art molecular biology laboratory based in the University of Leeds. You will be joining a vibrant, successful and growing research group focused on this and overlapping areas. 

Entry requirements

Applications are invited from candidates with or expecting a minimum of a UK upper second class honours degree (2:1), and/or a Master's degree in biological sciences, including bioengineering, clinical, chemistry or physical sciences. Full training will be provided.

If English is not your first language, you must provide evidence that you meet the University’s minimum English Language requirements.

How to apply

Formal applications for research degree study should be made online through the university's website. Please state clearly in the research information section that the PhD you wish to be considered for is the ‘Detecting and diagnosing breast cancer with DNA entrapment and nanopore detection’ as well as Dr James L Thorne as your proposed supervisor.

We welcome scholarship applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates.  All scholarships will be awarded on the basis of merit.

If you require any further information please contact the Graduate School Office e: maps.pgr.admissions@leeds.ac.uk