Professors Xiangmin Xu and Rozanne Sandri-Goldin, in collaboration with Professors Bert Semler and Todd Holmes at the University of California, Irvine, School of Medicine, were awarded a three-year, $4.3 million Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative grant. Working together with a "dream team" of US and Chinese scientists, they will lead the development of a new brain mapping tool for neuroscience research.
The mapping tool is based on genetically engineered herpesviruses. Herpes simplex virus (HSV) type 1, strain 129 (H129) will be harnessed as an anterograde, monosynaptic viral tracer with high labeling efficacy and low toxicity for neural circuit analysis.
Current versions of genetically modified H129 herpesviruses are limited primarily by high virulence and toxicity. We have a comprehensive plan to reduce the toxicity and also to enhance signal outputs and generate variants carrying different functional payloads. Ultimately, we will be able to create a new set of safe, effective and validated anterograde-directed viral vectors."
Xiangmin Xu, Professor, University of California, Irvine, School of Medicine
Expected to have broad impact, the new tool will be made available through the UCI Center for Virus Research where it can be disseminated to the entire neuroscience community.
"The development of trans-synaptic viral tracers is an important component of the BRAIN Initiative," said Xu. "At present, the lack of viral-based anterograde, monosynaptic tracing tools with high signal strength and low toxicity is a critical gap in neuroscience, preventing researchers from gaining a full understanding of how the brain works."
The team is excited about the prospect that new recombinant H129 viral vectors will lead to transformative tools for neuroscience research, and in the more distant future, clinical applications for human diseases such as Alzheimer's disease, Parkinson's disease and epilepsy. Xu and Sandri-Goldin have assembled a collaborative, interdisciplinary team composed of virologists and systems neuroscientists to develop the new neural analysis tool. Other principal investigators include Professor Gregory D. Horwitz from the University of Washington and Professor Min-Hua Luo from the Wuhan Institute of Virology, Chinese Academy of Sciences.
Their research proposal, "Genetically engineered anterograde monosynaptic viral tracers for multi-species neural circuit analysis," was submitted in response to a special RFA as part of the BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain.