Evaluation of MCT1s role in chromatin remodelling and metabolomics changes involved in cancer p[...]

Job Description

Monocarboxylate transporter 1 (MCT1) is a transmembrane protein involved in cell metabolism, mediating the transport of monocarboxylates (such as pyruvate and lactate) across the plasma membrane. Increased plasma membrane expression of MCT1 (PM MCT1) has been reported in several cancer types, including pancreatic cancers, and is associated with worse prognosis, reduced recurrence-free, and overall survival. Interestingly, although the nucleus is not a usual location for MCT1 based on current knowledge, recent studies have reported nuclear MCT1 (nMCT1) expression in endometrial and soft sarcoma cancers. Patients with nMCT1 tend to have longer overall survival than those without it.

Therefore, this project aims to better understand the significance of MCT1 localization and its potential effects on treatment outcomes for pancreatic ductal adenocarcinoma (PDAC) patients. The approach involves engineering cancer cell lines (Ishikawa and HEC1A) with MCT1 targeted specifically to the nucleus (nMCT1) or plasma membrane (PM MCT1) using CRISPR-Cas9 technology combined with molecular cloning. The engineered cell lines will undergo various in vitro analyses, including immunofluorescence, western blotting, and electron microscopy, to characterize subcellular localization and expression levels.

Metabolic profiling of these cell lines will be performed using mass spectrometry, with data analysis conducted using R or other relevant bioinformatics tools. Changes in chromatin remodeling will be assessed via ATAC-sequencing. The results from metabolomics and chromatin remodeling studies will be compared and correlated to explore the relationship between MCT1 localization, metabolism, and chromatin structure.

By the end of this interdisciplinary project, the student will acquire sought-after wet lab and bioinformatics skills, preparing them for post-doctoral positions.

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or equivalent qualifications outside the UK, in a relevant discipline.

How to Apply

For application details, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries can be directed to the primary supervisor. Please select PhD Cancer Sciences when submitting your application.

International students may have the opportunity to undertake an accredited teaching certificate alongside their research or to study a master’s before progressing to a PhD with our Integrated PhD program. More information is available on our international postgraduate researchers page.

Equality, Diversity & Inclusion

Our commitment to equality, diversity, and inclusion is fundamental to the success of The University of Manchester. The full statement can be found at https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/.

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