Grant: Operating Grant - PA: Genetics (Bridge Funding: Research Priorities)

Our brain consists of billions of nerve cells that communicate with each other to conduct complex tasks. The nerve cells use a cellular interface called synapse to send and receive information. Synapse contains many different types of proteins, each of which plays different roles for a synapse to function normally. If the synaptic structure is abnormal, nerve cells cannot communicate correctly, and brain function will be severely affected. Indeed, abnormal structure and function of synapses are often observed in the brains of patients with various neurological disorders, including intellectual disability. Currently, few therapeutics are available for these neurological disorders, partly because of the lack of understanding of how synapse is assembled and how its abnormality leads to these diseases. Therefore, we urgently need to increase our knowledge of basic mechanisms of synapse formation. We tackle this important issue by using nematode (C. elegans) as a genetic model organism. C. elegans has a simple nervous system, yet its nerve cells and synapses are highly similar to those of humans. Historically, many studies have proven that the discoveries made in C. elegans nerve cells and synapses can be directly transferred to understand how our nerve cells and synapses develop. Specifically, we focus on studying a gene called Calcium/calmodulin-dependent protein kinase II (CaMKII), whose mutations in humans are highly associated with various neurological disorders including intellectual disabilities. Our current data strongly suggests that CaMKII plays a crucial role in assembling multiple proteins into the functional synapses. Uncovering the novel functions of CaMKII in synapse formation will help us better understand how our brain develops, and how mutations in CaMKII cause various neurological diseases, which are the first steps toward the future development of the therapeutics.