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UCI School of Medicine researchers lead an international team for $4.3M NIH BRAIN Initiative award for new brain mapping tool

Xiangmin Xu
UCI School of Medicine
Professor Xiangmin Xu, in collaboration with UCI Professors Rozanne Sandri-Goldin, Bert Semler and Todd Holmes, was awarded a three-year, $4.3 million Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative grant.

Genetically engineered herpesvirus is a promising vehicle for anterograde neuronal circuit tracing

Irvine, CA - September 26, 2019 – 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,” said Xu.  “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.”

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.

About the NIH BRAIN Initiative

The Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative is aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a revolutionary new dynamic picture of the brain that, for the first time, shows how individual cells and complex neural circuits interact in both time and space. Long desired by researchers seeking new ways to treat, cure, and even prevent brain disorders, this picture will fill major gaps in our current knowledge and provide unprecedented opportunities for exploring exactly how the brain enables the human body to record, process, utilize, store, and retrieve vast quantities of information, all at the speed of thought. For more information, visit: https://www.braininitiative.nih.gov/

About the UCI School of Medicine

Each year, the UCI School of Medicine educates more than 400 medical students, as well as 200 doctoral and master’s students. More than 600 residents and fellows are trained at UC Irvine Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and master’s degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/master’s in public health, or an MD/master’s degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.

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