A fully funded 3-year PhD studentship is available to work with Dr Natividad Gomez-Roman at the University of Strathclyde in Glasgow, UK. You must be available to start this PhD 1st March 2023
Our group investigates the primary brain tumour glioblastoma (GBM), one of the most aggressive and incurable tumours in adults. Treatment comprises surgery, radiation, and chemotherapy (temozolomide). Even with this aggressive therapy, tumours inevitably recur, conferring a life expectancy of approximately one year. Intensive research using conventional preclinical models, such as cells are grown in two-dimensional conditions (plastic dishes) or as neurospheres, have identified multiple molecular targeted agents which have all failed in the clinic. Failure in the clinical translation of these agents imply that the conventional preclinical models used are not representative of GBM or its response to treatment. To elicit improved therapies for GBM patients and improve the poor survival rates, research in our group has focused in the development of appropriate models that better recapitulate the GBM microenvironment and evaluate how these cells respond to treatment.
Using a three-dimensional GBM model developed in our laboratory that recapitulates key clinical features including cell morphology, migration, and clinical response to molecular targeted therapies, we have observed a protective effect of cholesterol on GBM cells to radiation treatment and to drugs that induce lethal premature mitosis. High cholesterol levels have been implicated in several types of cancers including GBM, with tumour cells relying heavily on cholesterol for growth and survival. Cholesterol pathway upregulation is also associated with poor prognosis in GBM patients. The powerful influence of cholesterol on GBM biology is perhaps not surprising as the brain is the most cholesterol-rich organ of the body, where nearly 20% of total body cholesterol can be found. The aims of this project are to investigate how cholesterol regulates GBM growth and survival, to delineate cholesterol-related mechanisms of treatment resistance and identify novel therapeutic strategies to improve patient outcomes.
All applicants should have either a first-class undergraduate degree (or equivalent) or an upper-second class with a Masters in cancer sciences, biosciences or biomedical/biological disciplines. An English Language qualification for international students is required.
Techniques used:
The student will be trained in a wide range of laboratory techniques including cell culture of human patient-derived cell lines in conventional 2D and specialised 3D conditions and the analysis of cell viability, clonogenic survival, protein and mRNA expression, immunofluorescence imaging, and the response to ionizing radiation. Training of in vivo techniques such as intracranial injection of human glioblastoma cells, delivery of drugs via oral and peritoneal delivery and monitoring of mice in orthotopic brain tumour models. The student will also learn the fundamental concepts of radiation biology and statistics, as well as learning a wide variety of statistical analysis software such as GraphPad Prism and R.
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