Work Package 2

In vitro investigations of brain endothelial cell receptor internalization and trafficking pathways

Principal Investigator: Morten Schallburg Nielsen, Department of Biomedicine, Aarhus University

This work package deals with analysis of the receptor-mediated transport systems in brain endothelial cells, which have the potential to mediate transcytosis of nanocarriers and antibodies. Previous studies using the Transferrin receptor and LRP1 (Low density lipoprotein receptor-related protein1) have succeeded in transporting drugs across the endothelium.

In this work we will characterize different subcellular trafficking routes of known and novel receptors in brain endothelial cells. Currently, we are focusing on the recycling receptor Transferrin receptor and the retrograde transported mannose-6-phosphate receptor. The work will furthermore include a detailed classification of the endo-lysosomal system and functional internalization mechanisms in in vitro models of the blood-brain barrier.

The aim is to understand the receptor-mediated transcytosis mechanism in details in order to select the optimal receptor system for drug delivery to the brain.

Our studies are primarily based on state-of-the-art imaging systems such as confocal, spinning disk, high content screening and TIRF microscopy in combination with in vitro blood-brain barrier models.