Direct molecular-scale imaging of glycoimmune checkpoints in situ: A super- resolution microscopy platform for visualizing galectin-glycan lattices and membrane receptors

Lectin-glycan interactions play a critical role in regulating membrane receptor signalling and modulating immune cell function. These regulatory mechanisms, called glycoimmune checkpoints, have recently emerged as novel therapeutic targets to enhance antitumor T cell responses. Understanding the molecular patterns, spatial interactions and, organisation displayed by glycoimmune checkpoints might have major influences on signalling mechanisms and in the design of novel therapeutic strategies. My recent ground-breaking research has enabled molecular-scale super-resolution fluorescence microscopy with an unprecedented level of detail in intact cells. I propose to develop a novel integrative super-resolution imaging platform for direct imaging of glycoimmune checkpoints in situ, providing direct visualization of galectin- glycan lattices and membrane receptors. I will address the following questions: - How are glycans and glycosylated receptors distributed on the cell surface at the molecular scale? - Upon galectin treatment, can we observe a well-defined galectin-glycan lattice at the cell membrane? - What are the characteristics of such galectin-glycan lattice, specifically what are the effects of different galectins on the spatial arrangement of glycans and receptors? These findings will have an important impact on the development and assessment of novel immunotherapeutic approaches targeting glycosylated receptors with great potential for downstream translational studies.