Diagnosing breast cancer with DNA entrapment and nanopore detection

Summary

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.

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

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