Thomas Daugbjerg Madsen awarded Novo Nordisk 2021 Postdoctoral Fellowship for Research Abroad
Postdoctoral researcher Thomas Daugbjerg Madsen has been granted DKK 3,997, 557 over 4 years.
Institution abroad: NIH National Cancer Institute, Bethesda, Maryland, United States.
Danish host institution: University of Copenhagen, Department of Cellular and Molecular Medicine
Project title: Regulation of endocytic receptors by dynamic sialylation resolved by real-time intravital microscopy
Thomas' interview about the project: “Protein glycosylation and subsequent sialic acid capping (sialylation) is a very complex and widespread post-translational modification that regulate protein functions. Emerging evidence suggest that this is a reversible and dynamic process that allows the cell to control not only protein functions but also recycling of cell surface proteins after endocytosis (i.e. process of uptake of external substances and membrane proteins into the cell).
My project explores molecular switching of receptor glycans and sialic acid capping in vivo using real-time intravital microscopy in conditional mice mutants in three different endocytic organ/receptor-systems. The project builds on my line of research and my discoveries of site-specific glycosylation of a group of the endocytic LRP receptors where sialylation serves as a switch between high- and low-affinity states of the receptors. This regulatory element of the LRPs is crucial in several important physiological processes such as cholesterol-metabolism and kidney function. The laboratory at NCI/NIH where I am going has specialized expertise in real-time intravital microscopy that is central for my project, and I will be trained in this cutting-edge techniques which will both provide me with real-time imaging of receptor/ligand trafficking. Importantly, I will bring this expertise back to Denmark with the aim of establishing a platform for intravital studies of glycoprotein trafficking. My project will undoubtedly have profound impact on our general understanding of the regulation of receptor functions and provide new avenues for treatment of diseases such as hypercholesterolemia, renal insufficiency, and Alzheimer’s disease.”
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