The human brain is made up of billions of neurons that connect precisely through 100 trillion+ specialized junctions called synapses. If a brain is considered a dedicated computer, synapses are the nodes relaying information from neurons to other targets. These synapses are tiny in size (<100 nm mostly) but enormously complex and diverse in their molecular composition, structural morphology and physiological properties. So, synapses are distinct in different brain circuits where distinct behaviors are executed.  

Fascinated by the complexity and diversity of synapses, the Zhang lab strives to understand the molecular codes behind them. The obvious candidates for establishing such codes are a group of synaptic organizing proteins that mediates specific synaptic recognition and differentiation between two neurons. The diversity of proteins is expanded by different isoforms created by alternative mRNA splicing. Yet how post-translational modifications upon the synaptic organizing proteins contribute to the complexity remains largely unexplored. The lab recently discovered an evolutionarily conserved glycosylation (heparan sulfate polysaccharides) on the core synaptic organizing protein neurexin. Then it defined the functional requirement of this glycan for the normal synaptic structure and function. Now, the lab aims to elucidate how glycans increase the complexity of molecular codes governing synaptic specificity and diversity.
 
Multiple model systems are adopted to address the lab’s questions, such as cultured neurons and transgenic mice. A wide range of interdisciplinary techniques are applied, including but not limited to molecular biology, biochemistry, electrophysiology and mouse behavioral observation. In particular, the lab has set up the methods of sub-diffraction fluorescence-imaging and serial block-face scanning electron microscopy. These robust tools allow us to analyze the molecular architecture and structural morphology of synapses at nanoscale. Combining its expertise in glycobiology and synapse development, the lab expects to gain insights to how glycan-based molecular processes govern synapse development and provide a foundation for deriving novel therapeutic approaches to correct imbalances in the synaptic pathway in neuropsychiatric disorders.

Source: https://case.edu/medicine/neurosciences/people-research/faculty-name/peng-zhang