Molecular Systems Biology of the Synapse

We explore the protein networks at synapses to understand the molecular basis of neuronal circuits and brain function.

Visualization of a synaptic protein network (adapted from van Oostrum et. al. Cell 2023)

Brain function relies on communication among neurons via specialized junctions called synapses - tiny structures (~1 cubic micrometer) that are housed in the expansive axonal and dendritic arbors. Neurons build and diversify synaptic contacts using a plethora of protein combinations that define synaptic functional properties.

Molecular basis of neuronal communication
Our focus is to associate synaptic protein dynamics with neuronal function and behavior. We aim to understand how protein networks determine synapse type-specific connectivity, coordinate the development of neuronal circuits and rewire during aging and neurological disorders.

Across scales from molecules to phenotypes
We integrate molecular neurobiology with systems neuroscience and combine state-of-the-art mass spectrometry-based proteomics technologies with fluorescence activated sorting and in vivo labelling of defined synaptic populations within neuronal circuits.

Implications for neurological disease
Dysregulation and dysfunction of synaptic proteins play a central role in the pathogenesis of neurodevelopmental and neurodegenerative diseases. Investigating type-specific synaptic proteomes and their interactions provides insights into the molecular mechanisms underlying disease progression and may facilitate the development of targeted therapies.