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In this project, we investigate the protein-induced aggregation of synaptic vesicles, known as the synaptic vesicle cluster (SVC). SVCs form in the synapse through liquid–liquid phase separation and serve both as a storage reservoir for neurotransmitter-filled vesicles and as a regulatory hub for exocytosis and endocytosis.

We use controlled in vitro model systems consisting of vesicles and proteins to decipher the biophysical principles underlying SVC formation and dynamics. In particular, we focus on the roles of the proteins synapsin and alpha-synuclein.

Our studies employ coherent X-ray diffraction and imaging, using highly brilliant radiation from free-electron lasers (XFELs) and synchrotron sources. With X-ray photon correlation spectroscopy, for example, we can investigate the motion and transport of vesicles within the clusters under physiological conditions. Using ultrashort and tightly focused XFEL X-ray pulses, we can also resolve the structure of individual vesicles.

Beyond their physiological function, we are also interested in whether SVC condensates may play a role in the formation of pathological fibrils associated with neurodegenerative diseases.