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Click here to search FindAPhD.com for PhD studentship opportunitiesAbout the Project
Pancreatic Ductal Adenocarcinoma (PDAC), which develops from cells lining pancreas ducts, represents 95% of all pancreatic cancer cases. In the UK alone, PDAC is the 11th most common cancer with ~10,000 new cases diagnosed every year. It has abysmal life-expectancy with only 7% surviving the first five years[1]. PDAC death rates are constantly on the rise and it is projected to become the second most lethal cancer by 2030[2].
Monocarboxylate transporter 1 (MCT1) is a transmembrane protein involved in cell metabolism and mediates transport of monocarboxylates (such as pyruvate and lactate) in both directions across plasma membrane. Increased plasma membrane expression of MCT1 (PM MCT1) has been reported in several cancer types including pancreatic[8] cancers and are associated with worse prognosis, reduced recurrence-free and overall survival. Interestingly, although nucleus is not a usual location for MCT1 (based on current knowledge on its function), we and others reported nuclear MCT1 (nMCT1) expression in endometrial[7] and soft sarcoma[9]. Both studies showed that patients with nMCT1 have a longer overall survival than the patients without it. Therefore, it is important to improve knowledge on the significance of MCT1 localisation and evaluate its potential effects on treatment outcome for improving PDAC patients’ survival. For this purpose; we aim to 1. subject PDAC tissues to IHC and relate protein localisation to survival (for patients with/without nMCT1), 2. perform RNA-seq on a. BxPC3 (nMCT1 model) and Mia-Paca2 (PM MCT1 model) cells and b. genetically modified PDAC cells over-expressing nMCT1 or PM MCT1, 3. measure sensitivity to chemotherapy(FOLFIRINOX) in nMCT1 expressing cells and 4. test efficacy of MCT1 inhibitors for improving chemotherapy outcome in chemo-resistant PM MCT1 cells.
Eligibility
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a biological discipline including Biology, Neuroscience and allied fields, Pharmacology, Molecular Biology. Applicants with experience in basic molecular techniques and an interest in neurodevelopment are encouraged to apply.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title - PhD Neuroscience.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/international-phd/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
Funding Notes
References
2. Vanitha N Sivalingam*, Ayşe Latif *, Sarah Kitson, Rhona McVey, Henry Kitchener, Katherine G Finegan, Kay Marshall, Michael Lisanti, Federica Sotgia, Ian J Stratford, Emma J Crosbie. ‘Hypoxia and hyperglycaemia contribute to metformin resistance in endometrial cancer’. *Equal contribution by both authors. British Journal of Cancer (Nature Publishing Group), January 2020.
3. Salem, A., Little, R., Latif, A., Featherstone, A., Babur, M., Peset Martin, I., Cheung, S., Watson, Y., Tessyman, V., Mistry, H., Williams, K., O’Connor, J. ‘Oxygen enhanced-MRI is feasible, repeatable and detects radiotherapy induced change in hypoxia in xenograft models and in patients with non-small cell lung cancer’, Clinical Cancer Research.2019 Mar; DOI:10.1158/1078-0432.CCR-18-3932
4. Ayşe Latif, Amy L Chadwick, Sarah J Kitson, Hannah J Gregson, Vanitha N Sivalingam, James Bolton, Rhona J McVey, Stephen A Roberts, Kay M Marshall, Kaye J Williams, Ian J Stratford, Emma J Crosbie. ‘Monocarboxylate Transporter 1 (MCT1) expression is an independent prognostic marker in endometrial cancer’. BMC Clinical Pathology; 2017 Dec; 17(27)
5.Andrew James, Waseema Patel, Zohra Butt, Magretta Adiarnah, Raga Dakhel, Ayşe Latif, Caroline Uggenti, Eileithyia Swanton, Hiromi Imamura, Ajith Siriwardena and Jason Bruce. ‘The plasma membrane calcium pump in pancreatic cancer cells exhibiting the Warburg effect relies on glycolytic ATP’. The Journal of Biological Chemistry; 2015 Aug; 290(41): 24760-24771.
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