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PhD in the Leeds Institute of Cancer and Pathology Faculty of Medicine and Health University of Leeds Understanding the response to pre-operative therapy in colorectal cancer through phenotypic and genotypic analysis Supervisors: Dr. Nick West, Prof. Steve Evans, Dr. Henry Wood Funding: LICAP studentship A PhD studentship is available for UK and EU citizens only, with an expected start date of October 2017. The studentship will attract an annual tax-free stipend of £14,553 for up to 3 years, subject to satisfactory progress and will cover the UK/EU tuition fees. You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. The project would suit a student with a background in biochemistry, chemistry, physics, engineering or computer sciences. Candidate whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are: • • British Council IELTS - score of 6.5 overall, with no element less than 6.0 TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23. Research Project: Colorectal cancer is common with over 40,000 new cases diagnosed annually. Patients are often treated with pre-operative radiotherapy, chemotherapy or combination chemoradiotherapy. This project aims to gain further understanding of the patterns and mechanisms of response to radiotherapy, chemotherapy and chemoradiotherapy in colorectal cancer by investigating the patterns of cell death, the host response and the changes induced in the genetic profiles of these cancers using material from clinical trials archived in Leeds. The specific objectives are to: 1. Describe the morphological patterns of cell death in detail using digital pathological analysis of resected tumours (patterns we have previously observed include shrinkage and fragmentation) and tumour cell density, a novel in-house technique1. 2. In collaboration with our new MRC single cell centre using novel automated microfluidic devices, cell isolation and characterisation techniques developed in house2,3, the student will characterise the numbers and phenotype of tumour cells before and after different types of pre-operative treatment. 3. Identify host immune responses involved in the different patterns of regression by analysing immune cell populations before and after treatment using immunohistochemistry. 4. Identify the genomic changes present in the tumour before and after treatment using next generation sequencing technologies for specific targeted mutations and copy number changes. 5. Determine whether phenotypic, immune and genomic changes noted before treatment can be used to develop novel markers to predict the degree and type of response to treatment. Patient material from a variety of national clinical trials is available for analysis including studies of radiotherapy alone (MRC CR07 - approximately 500 cases), chemotherapy alone (FOxTROT - 150 colon cancers in phase II, 900 in phase III, BACCHUS - approximately 30 rectal cancers) and chemoradiotherapy (ARISTOTLE - approximately 600 cases). Full ethical approval is already in place for the planned work. References: 1. West N, et al. Quantitative assessment of tumour cell density in rectal cancer following three different preoperative therapies compared to surgery alone. Journal of Clinical Oncology 28, supplement, abstract 3651, 2010. 2. Peyman, SA, et al. Expanding 3D geometry for enhanced on-chip microbubble production and single step formation of liposome modified microbubbles. Lab Chip 12, 4544-52, 2012. 1. 3. Peyman, SA, et al. On-chip preparation of nanoscale contrast agents towards high-resolution ultrasound imaging. Lab Chip (2015). doi:10.1039/C5LC01394A Environment: The student will be based in the University of Leeds in the Pathology and Tumour Biology Section, Leeds Institute of Cancer and Pathology and also in Molecular and Nanoscale Physics at the School of Physics and Astronomy. Training will be provided in the relevant technical areas. For more information about the group visit our webpages at: http://medhealth.leeds.ac.uk/info/970/pathology_and_tumour_biology http://www.mnp.leeds.ac.uk/steve-evans.html How to apply: To apply for this scholarship applicants should complete a Faculty Scholarship Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School [email protected] We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to [email protected] by no later than Friday 7 July 2017 If you have already applied for other scholarships using the Faculty Scholarship Application form you do not need to complete this form again. Instead you should email [email protected] to inform us you would like to be considered for this scholarship project. Any queries regarding the application process should be directed to [email protected]. To discuss the project informally please contact Dr. Nick West ([email protected]) with a CV. Closing date for this studentship is Friday 7 July 2017