About the Project
Supervisors: Tim Forshew, Javier Herrero, Stephan Beck
Application Deadline: Applications accepted until 5.00pm 29th May 2015
Eligibility for Non-clinical PhD Studentships: Requires a minimum of an upper 2nd class Honours Degree in a relevant discipline, some research experience, need to qualify as UK/EU fee payers and meet UCL general admissions criteria. These four year PhD studentships, funded by Cancer Research UK, includes a competitive training salary, consumables, a travel allowance, and tuition fees (home/EU rate) paid in full.
Project description:
The field of precision medicine is rapidly evolving as next generation sequencing (NGS) platforms develop. The discovery that solid tumours release DNA into peripheral fluids such as blood plasma and Cerebrospinal fluid (CSF) has opened the possibility of non-invasive cancer genetic analysis.
Currently the biggest challenge to this field of "liquid biopsy" is the limited quantities of DNA released and the often low tumour allele fractions. NGS methods are error prone and typically struggle to detect mutations present below ~1% allele fraction.
A number of methods have recently been developed that use tagging of single molecules to effectively overcome the errors induced during library preparation and sequencing. None of these methods though have yet been optimised to work efficiently with the small quantities of DNA often released into circulation.
Following review of the literature the student would first establish one or multiple single molecule sequencing methods within UCL. They would then look to optimise how efficiently individual DNA molecules were tagged.
The developed methodology would then be used to screen for cancer mutations in various patient samples such as Cerebrospinal fluid and blood plasma. A broad collection of patient samples have, and continue to be biobanked within UCL enabling a range of different clinical questions to be addressed. Two areas of focus within the Forshew lab are childhood brain tumours and sarcoma. Use of the above methods may enable a range of applications from non-invasive cancer diagnosis and treatment monitoring to the detection of relapse and tumour evolution.
If the method were suitably efficient the student would also be able to perform single cell sequencing for different tumour types. They may test the ability to detect tumour heterogeneity by sequencing single cells and determine whether this is also represented within the circulation. The student may also apply the method to a range of additional questions including circulating tumour cell sequencing and single molecule bisulphite sequencing if appropriate.
Key skills
The successful candidate must be highly motivated, an excellent problem solver and keen on both computational and molecular research.
Please email [Email Address Removed] for a full reference list
Application Procedure:
To apply, please send the following pieces of information to [Email Address Removed] providing the project number(s) and title* in the subject line.
1. An electronic CV highlighting your academic achievement and research experience, as well as stating your nationality and usual country of residence
2. Academic transcripts
3. A short summary (<500 words) detailing how your research interests and academic background matches the project
4. Contact details for two referees
*One application per candidate please. Although you may list more than one project per application, your short summary will need to specify how your background/interests fit each project.
Application Deadline: Applications accepted until 5.00pm 29th May 2015
Initial receipt of your application will be acknowledged. If you have not been contacted for an interview by the end of June you can assume that you have not been successful. Queries about the application procedure or recruitment process should be directed to: [Email Address Removed]
References
References:
Dawson, S.-J., Tsui, D. W. Y., Murtaza, M., Biggs, H., Rueda, O., Chin, S.-F., Dunning, M., Gale, D., Forshew, T., Mahler-Araujo, B., Rajan, S., Humphray, S., Becq, J., Halsall, D., Wallis, M., Bentley, D., Caldas, C. and Rosenfeld, N. (2013) ‘Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer’, New England Journal of Medicine, 368(13), pp. 1199–1209. doi: 10.1056/nejmoa1213261
Forshew, Murtaza, Parkinson, Gale, Tsui, D., Kaper, Dawson, S.-J., Piskorz, A., Jimenez-Linan, Bentley, Hadfield, May, A., Caldas, Brenton, J. and Rosenfeld (2012) ‘Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA’, Science Translational Medicine, 4(136), doi: 10.1126/scitranslmed.3003726
Murtaza, M., Dawson, S.-J., Tsui, D., Gale, D., Forshew, T., Piskorz, A., Parkinson, C., Chin, S.-F., Kingsbury, Z., Wong, A., Marass, F., Humphray, S., Hadfield, J., Bentley, D., Chin, T. M., Brenton, J., Caldas, C. and Rosenfeld, N. (2013) ‘Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA’, Nature, 497(7447), pp. 108–112. doi: 10.1038/nature12065