The aim of the project is to analyse the nose to brain mechanisms of antibodies transport, their interaction with epithelial, endothelial and neuronal cells, their distribution in the central nervous system, and potential pathways for IgG clearance and elimination. We will perform single molecule imaging experiments to track single antibodies in living cells with nanometre accuracy by means of high sensitivity fluorescence detection methods. The type of trafficking pathway will be determined according to the type of motion (expected Brownian diffusion for extracellular-including lateral diffusion on the plasma membrane-, directed motion for intracellular active transport). The IgG’s interaction with specific receptors will be monitored in real time in different types of cells, and a standard protocol will be set up to evaluate designed IgG with different properties. We will employ light-sheet based microscopy techniques used to study whole mouse brain and spinal cord micron-scale neuroanatomy to follow any specific distribution pattern in the brains of mice with the diverse antibodies.
