Diagnosing breast cancer with DNA entrapment and nanopore detection

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

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &lsquo;Diagnosing breast cancer with DNA entrapment and nanopore detection&rsquo; as well as&nbsp;<a href="https://physicalsciences.leeds.ac.uk/staff/156/dr-james-l-thorne">Dr James Thorne</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p>&nbsp;</p>

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.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.5 overall with at least 6.0 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<p><strong>Self-Funding Students are welcome to apply.</strong></p> <p><strong>UK&nbsp;students</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/138-leeds-doctoral-scholarships-2021-january-deadline">Leeds Doctoral Scholarship (January deadline)</a>&nbsp;is available to UK applicants. &nbsp;<a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Non-UK students</strong>&nbsp;&ndash;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a>&nbsp;is available to nationals of China. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a>&nbsp;is available to support US citizens. &nbsp;<a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p>

<p>For further information regarding your application, please contact Doctoral College Admissions by&nbsp;email: ENV-PGR@leeds.ac.uk, or by telephone: +44 (0)113 343 5057.</p> <p>For further information regarding the&nbsp;project, please contact Dr Matteo Castronovo: M.Castronovo@leeds.ac.uk</p>