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 will first combine CRISPR-Cas9 technology with molecular cloning to engineer cancer cell lines (Ishikawa and HEC1A) with MCT1 protein targeted specifically to the nucleus (nMCT1) or plasma membrane (PM MCT1). We will then subject these cell lines to a number of in vitro methods (e.g. immunofluorescence, western blotting, electron microscopy) to characterise subcellular localisation and expression levels in engineered cell lines. Metabolic profile of the engineered cell lines with nMCT1 wand PM MCT1 will be performed using mass spectroscopy and data analysis will be performed using R package. Changes in chromatin remodelling will be assessed using ATAC-sequencing. Results of metabolomics and chromatin remodelling will be compared and correlated to evaluate correlation between MCT1 subcellular localisation, changes in metabolism and chromatin structure by using R or any other relevant bioinformatics tools. By the end of this interdisciplinary project, the selected student will be equipped in sought after wet lab and bioinformatics skills for post-doctoral positions.
Eligibility
Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.
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. Please select PhD Cancer Sciences when submitting your application.
For international students, we offer the opportunity for you to undertake an accredited teaching certificate whilst carrying out your research with our PhD with Integrated Teaching Certificate. We also offer self-funded international students the chance to study a master’s before progressing onto a PhD with our Integrated PhD. Visit our international postgraduate researchers page to find out more.
Equality, Diversity & 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/
