Neuron-glia biology in neurodegeneration.

"The eye as a window to the brain” is the central theme of my research. I envision to focus on the interrelatedness of neurobiology and ophthalmology and to exploit this cross-over of disciplines to enrich fundamental research into central nervous system (CNS) function. By concentrating on the retina-brain axis, I will unravel mechanisms of intercellular communication in the CNS, with emphasis on neuronglia interactions. I will study these interactions both under physiological conditions and in the context of neurodegeneration. My ambition is to develop a strong fundamental research program that aims at answering the following research questions: - What is the role of extracellular vesicles as messenger organelles in neuron-glia interactions? - What is the function of these vesicles in cell-cell communication during inflammation? - Do these vesicles act as ‘Trojan horses’ governing prion-like spreading of protein aggregates? - Are these two phenomena connected? And if so, how? Because of its unique, advantageous anatomical organization, the visual system is an ideal model of the CNS to address these questions. My standing expertise in high-resolution (in vivo) imaging, electrophysiology of the visual system, primary retinal cell cultures and organotypic explants illustrates that I am well positioned to steer this research. Adding to the novelty of this research, I will employ a new, self-developed paradigm to study protein propagation in the mouse visual system, and also invest in technical development, by implementing an integrated workflow for flow cytometry-based sorting of extracellular vesicles and subsequent proteomics analysis of their cargo.