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Gang Han awarded NIH EUREKA grant for development of ‘optogenetic’ tool

High-impact research promises new method of studying neuropsychiatric diseases

Gang Han, PhD, assistant professor of biochemistry & molecular pharmacology at UMass Medical School, has received a $1.3 million EUREKA (Exceptional, Unconventional Research Enabling Knowledge Acceleration) grant from the National Institute of Mental Health to develop light activated nanoparticles that can be used to image live brain tissue. These novel nanoparticles will form the basis of a new “optogenetic” tool that promises to help researchers map and decode previously inaccessible neural circuitry deep in the brain using near infrared light. Insights gleaned from this breakthrough technique will further understanding of the relationship between neural circuit activity, behavior and neuropsychiatric diseases. The co-investigators on the grant include Carlos Lois, MD, PHD, professor of neurobiology, and Yang Xiang, PhD, assistant professor of neurobiology.

Understanding how the activities of certain neurons help to mediate behavior and influence disease is a prominent challenge in treating neuropsychiatric disorders. Optogenetics is an emerging technique designed to address this challenge. It combines recent breakthroughs in both optics and genetics to allow scientists to stimulate the activity of individual neurons in animal models. However, current optogenetic tools rely on fiber optic probes to transmit light and stimulate neurons in vivo. Because these probes have to be surgically inserted into the brain and attached to a power source, their practical use in animal models is greatly limited.

With the EUREKA grant, Dr. Han proposes to develop a wireless optogenetic technique using key advances his lab has made in lanthanide-doped upconversion nanoparticles (UCNPs). The advantage of these nanoparticles is that they can be turned on using low power, tissue-penetrating, near infrared radiation that is then converted to higher energy, visible light that can be seen through deep tissue. This means that they can be activated remotely and safely inside living animal models to stimulate and observe particular neurons or neural circuitry without the need for surgery or restrictive probes. This would provide scientists an important new tool for mapping and understanding the complex interaction between particular neural pathways and behavior.

“This strategy offers a potential paradigm shift to achieve true ‘wireless’ control of neuron activation and deactivation,” said Han. “The impact of such a new technique is impossible to overstate as it would allow us to study the relationship between neural circuitry activation and behavior, a possibility that even a few years ago was hard to image.”

The EUREKA grant is part of a program by the National Institutes of Health to fund exceptionally innovative research projects enabling the establishment of novel concepts and approaches to solve important problems or open new areas for investigation.

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