The primary objective of this EAGER project is to provide infrastructure that will have broad scientific and social impacts. The scientific information and reagents generated in this project will impact a wide range of scientific activities relevant to the NSF BRAIN Initiative. The protein interactions uncovered will provide the basis for hypothesis-driven research neurobiology programs in humans and model organisms. Discovery of the ensemble of molecular interactions of the synaptic cleft, and sharing these data and reagents with the scientific community, will provide stepping stones for many other projects, increasing the overall rate of discovery in neuroscience, developmental and structural biology, proteomics, and related fields. The PIs have a strong commitment to undergraduate teaching in their laboratories, and have extensive experience training undergraduate and minority students in research projects. Several aspects of the proposed BRAIN EAGER project, and the anticipated follow-up structural and functional studies of synaptic proteins, are ideally suited for such undergraduate projects. The interdisciplinary nature of our EAGER proposal, at the interface of neurobiology, cell biology, systems biology, bioengineering, bioinformatics, and molecular biophysics, will allow the PIs to expand their undergraduate research programs, and to proactively recruit undergraduate minority students into these programs, training the next generation of molecular neuroscientists. It is estimated that the human brain is composed of about 120 billion neurons, connected through more than 100 trillion synapses. Despite the astronomical number of possible connections, during development the brain is wired with exquisite precision so that brain circuits precisely integrate and process sensory inputs to generate proper motor outputs as well as behavior and social interactions. At the cellular and molecular level, each individual synapse requires the apposition of structurally and functionally matching pre- and post-synaptic protein pairs. Although there are trillions of synapses, each synapse is likely to be unique. Synaptic specificity is thought to arise from a code of specific interactions among adhesive molecules acting across the synaptic cleft. However, if a synaptic code does indeed exist, it is not known how it works, which synaptic molecules are involved, how they connect to each other, or their structures. The PIs will develop a high-throughput (HTP) program aimed at building an experimentally-validate protein interaction network of synaptic proteins and exodomains. The protein interactions and functions discovered in this project will provide a more comprehensive and unified view of the synaptic protein interaction network, which will enable the scientific community to determine whether a synaptic code may exist. New molecular pathways will be uncovered. These efforts to characterize the synaptic protein interaction network will provide innovative insights into brain circuit formation, and likely result in totally unexpected discoveries. These results will broadly inform cellular and molecular neurobiology and open the door to many interdisciplinary follow up studies.
|Effective start/end date||9/1/14 → 8/31/16|
- National Science Foundation (NSF)