Hypothesis: This fellowship will test the hypothesis that in MM cells galectin-3 and CD98 promotes proliferation and resistance to chemotherapy in MM cells and the permissive inflammatory tumour environmental in a beta1 integrin dependent manner. Aim: To determine the impact of galectin-3 and CD98 on beta1 integrin-mediated functions in MM cells in vitro and in vivo. Key beta1-integrin functions will be examined: cell proliferation, chemoresistance, ECM secretion and fibronectin matrix assembly. Manipulation of galectin-3/CD98/beta1 integrins in MM cells prior to co-culture with macrophages on macrophage phenotype will be examined. These results will inform the experimental crux of this fellowship - to determine the effect of intrapleural administration of an inhibitory agent (defined by the in vitro experiments) on mesothelioma growth and associated inflammation and fibrosis and mesothelioma sensitivity to chemotherapy . Efficacy of this agent will be assessed by PET/MRI in a murine model. We will address molecular mechanisms by examining in vitro cell signalling cascades and in vivo by novel imaging techniques. Medical Potential: to identify key molecules driving the inflammatory microenvironment and tumour propagation and to pharmacologically/ genetically inhibit these pathways. To drive this research forward to the creation of a novel treatment for malignant mesothelioma and to potentially improve the efficacy of existing treatments.