Investigation into the effect of desialylation on Galectin-9 interaction with tumour cell surfaces. (360G-Wellcome-201942_Z_16_Z)

Galectin-9 is known to possess immunomodulatory properties both inside and external to the cell, inducing both pro and anti-inflammatory responses. It was originally proposed as an eosinophil chemoattractant. Recently, the group I wish to work with have shown that galectin-9 induces apoptosis of specific T-cells and has therapeutic potential in targeting specific chemotherapy-resistant tumour cells. Galectin-9-carbohydrate lattices can be formed at the cell surface as a result of galectin-9 crosslinking with glycoconjugates and gangliosides. Many of the immunomodulatory functions of galectin-9 involves initial binding to membrane glycoproteins and glycolipids, leading to cytoskeleton-dependent actions such as apical polarization, apoptosis and autophagy. However, the mechanisms by which galectin-9-induced changes in cytoskeleton dynamics are poorly understood. In this study we will determine the effect of extracellular-galectin-9 treatment on ovarian and colon cancer cells, pre- and post-treatment with sialidase. Alteration of the surface glycosylation pattern on malignant cells potentially affects tumour immunity by directly influencing interactions with lectins on their surface. Therefore we will quantify a) galectin-9 binding; b) F-actin changes and c) apoptotic status of tumour cells, pre- and post-treatment with sialidase. These studies will provide insight into the structure-functional interaction between galectin-tumours to help understand the biological functions of galectin-9.