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  Assessment of the predictive value of plasma proteins in oesophageal adenocarcinoma treatment

   School of Medicine

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  Dr AJ Stewart  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Applications are invited for a Tenovus Scotland PhD studentship to start in October 2019. The project will be supervised by Dr Alan Stewart, Dr Swati Arya and Dr Peter Caie in the School of Medicine.

Oesophageal adenocarcinoma (OAC) is one of the leading causes of cancer mortality worldwide, with a poor 5-year survival rate (less than 15%). The UK has the highest rates of oesophageal cancer in Europe, (National Cancer Registry Report, 2014). It is asymptomatic in early stages and has no biomarkers for its early detection which leads to late diagnosis and poor prognosis resulting in high mortality rate. Incidence is increasing rapidly, with yearly increases of ~4% for females and ~5% for males over the last 20 years. The number of cases in UK is thus predicted to double by 2035, with an accompanying rise in the number of patients seeking treatment.

Curative therapy consists of surgery, either alone or in combination with adjuvant or neo-adjuvant chemotherapy or radiation, or combination chemoradiotherapy regimens (neo-CRT). Multimodal neo-CRT regimens have been shown to increase 5-year survival to 60% in responding patients, compared to chemotherapy alone. However, only a minority of patients respond to this treatment, meaning the majority (70-80%) of patients will experience treatment-related toxicity and delay to surgery with no clinical benefit. There are currently no clinico-pathological means of predicting which patients will benefit from neo-CRT treatment. There is therefore an urgent need to improve OAC disease management and treatment strategies.

The aim of this study is to identify plasma proteins which may be used as markers for prediction of OAC patient response to neo-CRT treatment in a reliable manner. Furthermore, the study will investigate these proteins with an aim to predict a more accurate prognosis than the current clinical gold-standards. Together with Dr Sally Shirran and the Mass Spectrometry Team at St Andrews, we have standardised a quantitative proteomic technique for analysis of blood plasma, Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS). This technique allows accurate and sensitive quantitative measurement of 1,000s of proteins in a particular sample. This approach can be directly utilised for the proteomic analysis of human plasma from OAC patients undergoing different forms of treatments (supplied by our collaborator, Dr Margaret Dunne, Trinity College Dublin). We will also apply machine learning algorithms that will analyse the large scale quantitative mass spectrometry data in combination with the anonymised clinico-pathological and patient history data to identify subsets of plasma proteins that can be used to predict an individual’s response to treatment and likely disease progression and outcome.

As such, the specific objectives of this studentship are as follows.
1. Quantitative proteomic analysis of plasma proteins obtained from the OAC patients before treatments.
2. Utilise a machine learning algorithm to identify groups of proteins that can be used to predict tumour regression in response to treatment and overall patient survival.
3. Design and validate an ELISA-based multi-biomarker “disease” activity assay that can be used to predict treatment response and prognosis in OAC.

The successful candidate will be based in the School of Medicine at the heart of the St Andrews Science Campus at North Haugh. The student will receive training in a very wide range of cellular and molecular techniques. Specifically, methodologies will include sample preparation for mass spectrometry, SWATH-MS analysis, ELISA and machine learning – knowledge of these techniques will position the student well for a career in medical research after their doctoral studies. The student will also benefit from the University’s GRADskills programme. This is an award-winning transferable skills programme, which includes courses relating to scientific communication, thesis/research article writing, statistics and intellectual property protection. They will also have the opportunity to regularly present their work and to attend external scientific meetings.

How to Apply
We are looking for enthusiastic candidates who hold a first or upper-second class degree (and/or an MSc/MRes degree) in Molecular & Cellular Biology, Biochemistry, Chemistry (Analytical) or a related subject from a recognised academic institution. Applicants with some degree of laboratory research experience are particularly encouraged to apply. To apply, please visit the University of St Andrews website and download the PhD application form. Full details on how to apply are given here:

Informal enquiries can be addressed to Dr Alan Stewart (E-mail: [Email Address Removed]). For more information please see our group website at

Funding Notes

The studentship is funded for 3 years with a tax-free stipend starting at £15,009 per annum. Tuition fees at the Home/EU rate will also be paid. There is no provision for overseas student fees.