About the Project
In this project you will perform a variety of experiments such as culture of CD36-positive, CD36 knock-out OSCC cells, normal oral keratinocytes (NOK) and NOK overexpressing CD36 with oxLDL or a range of dietary fatty acids (e.g. palmitic acid) and examine if this receptor regulates expression of a panel of EMT markers by RT-qPCR and immunoblotting. You will also incubate CD36-positive OSCC with blocking antibodies and/or JNK inhibitors before culture with lipids before examining expression of EMT markers and OSCC cell migration. In parallel, you will examine the expression of CD36 on a large cohort of paired human primary and metastatic OSCC available in our department using immunohistochemistry, and correlate this with clinical data to determine of CD36 expression is linked to poor outcome, tumour stage or metastatic risk.
Murine models of OSCC metastasis are relatively poor because orthotopic cancer models are restricted by the small size of the murine oral cavity and subcutaneous OSCC tumours do not represent the disease pathology. Our laboratory has extensive expertise in producing tissue engineered OSCC 3D models where cancer cell invasion and migration into collagen gels can be visualized and measured. You will use these models to assess a variety of drugs that may prevent CD36-mediated metastasis.
It is likely that up-take of high-energy lipid molecules by CD36-expressing cancer cells may dramatically alter their gene expression, in particular metabolic and plasma membrane synthesis pathways that are required for increased energy production required for motility and cell proliferation. To address the lack of data in this area you will perform global gene expression profiling on OSCC cells in the absence or presence of oxLDL and use bioinformatics tools to assess genes and pathways affected by lipid up-take, which will lead to new pathways of research in this area.
The combined findings of these studies will fill the knowledge gap in this area of research as well as identifying potential therapeutic agents.
Interested candidates should in the first instance contact (Dr Craig Murdoch [Email Address Removed])
How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply
Please clearly state the prospective main supervisor in the respective box and select School of Clinical Dentistry as the department.
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