Investigating the mechanism of action of dual antiangiogenic/ antineoplastic drugs using organotypic co-culture of fibroblasts and endothelial cells

An important feature of many types of cancer is the ability to develop abnormal angiogenesis (blood vessel formation); this allows cancer cells to gain access to nutrients and favours metastasis. One of the major challenges of cancer research is to understand the molecular mechanisms of tumour angiogenesis and develop effective drugs capable to prevent it.
The primary objective of this project is to evaluate the anti-angiogenic properties of synthetic compounds developed at the Institute of Cancer Therapeutics (University of Bradford) by setting up organotypic co-cultures of tumour fibroblasts and endothelial cells (EC). This is a novel in vitro technique which offers physiological advantages compared with the classic Matrigel angiogenesis assay. After 5 days of co-culture, the formation of EC tubules (initial blood vessel structures), in the presence or absence of anti-neoplastic drugs, can be assessed by CD31 immunostaining.

During the project, the PhD candidate will acquire skills in a wide range of laboratory techniques such as advanced tissue culture to maintain the stability of co-cultures, molecular biology (cellular infection for knock-down and overexpression experiments), immunostaining and confocal imaging to investigate the mechanisms of actions of the antiangiogenic drugs. To further investigate these actions, proliferation assays will be performed using ECs in the presence of the compounds showing the highest activity. These experiments will provide insight into specific antiangiogenic actions of selected compounds.

In addition, the student will gain experience in writing research reports (weekly lab meetings) and scientific presentation skills by giving short talks at the monthly research seminars in the School of Pharmacy and Medical Sciences.