Sep 14, 2018
Professor Anne Andrews
Professor Anne Andrews and alumna Dr Nako Nakatsuka lead team to develop a novel system to track brain chemicals. 
 
The team of researchers from UCLA and Columbia University developed a novel method for tracking the activity of small molecules in the brain, including the neurotransmitters serotonin and dopamine. Pairing tiny artificial receptors with semiconductor devices that are able to function in living tissue, the team was able to observe brain chemicals at a high level of detail. The method will help researchers understand brain chemistry in psychiatric disorders.
 
The research is part of the BRAIN Initiative, a large-scale collaboration among government, private industry, nonprofits, and numerous colleges and universities.
 
The team’s paper titled “Aptamer–field-effect transistors overcome Debye length limitations for small-molecule sensing” was published in the September 6, 2018 issue of the journal Science
 
Alumna Dr. Nako Nakatsuka (Ph.D. ’17 Andrews/Weiss groups) (pictured left), now a postdoc at ETH in Zürich with Professor Janos Vörös in the Laboratory of Biosensors and Bioelectronics, was the lead author UCLA professor of chemistry & biochemistry and psychiatry & biobehavioral sciences Professor Anne Andrews (pictured above) was the senior corresponding author. Co-authors were Dr. Kyung-Ae Yang and Professor Milan Stojanović at Columbia University, alum Dr. John Abendroth (Ph.D. ’18 Weiss group), now a postdoc in the lab of Professor Jennifer Dionne at Stanford, Chemistry & Biochemistry graduate students and postdocs in the Andrews/Weiss labs (Kevin Cheung, Xiaobin Xu, Dr. Hongyan Yang, and Chuanzhen Zhao), and postdocs in Professor Yang Yang’s lab in Materials Science and Engineering (Dr. Bowen Zhu and Dr. You Seung Rim), and UCLA distinguished professor of chemistry and biochemistry Professor Paul Weiss (pictured right)
 
From UCLA Newsroom (by Alice Walton):
 
UCLA-led team develops new system for tracking chemicals in the brain
 
Method will help researchers better understand psychiatric disorders
 
To observe chemicals in the brain in more detail than previous methods allowed, the scientists paired tiny artificial receptors with semiconductors that can function in living tissue. Nako Nakatsuka
 
UCLA and Columbia University researchers have developed a new method for tracking the activities of small molecules in the brain, including the neurotransmitters serotonin and dopamine.
 
“Understanding the fundamentals of how neurotransmission occurs will help us understand not only how our brains work, but what’s going on in psychiatric disorders,” said Anne Andrews, the study’s lead author, a UCLA professor of psychiatry and chemistry.
 
The research, which was published in the journal Science, is part of the BRAIN Initiative, a collaboration among government, private industry, nonprofits, and colleges and universities.

To observe chemicals in the brain in more detail than current methods allow, the team developed a new strategy: pairing tiny artificial receptors with semiconductors that can function in living tissue.

The idea for the project began 20 years ago. While researching serotonin, Andrews realized that the then-state-of-the-art methods for monitoring neurochemicals couldn’t provide data with sufficient quality, and she determined she needed a totally new technology.

Andrews (pictured right) envisioned coupling engineered receptors, to bind neurotransmitters, with a nanoscale transistor, to relay the information. A major hurdle, however, was that the required transistors, which are basic units of computers and cell phones, don’t work well in wet, salty environments.  

“The workhorse of any transistor is the semiconductor,” Andrews said. “But when you put it in saltwater, the salt ions — charged atoms — line up on the semiconductor surface, and shield it, preventing detection of electric field changes. This is known as the ‘salt-shield’ problem.”

Andrews collaborated with Paul Weiss, a UCLA distinguished professor of chemistry and biochemistry, and of materials science, and with Yang Yang, a professor of materials science at the UCLA Samueli School of Engineering.

Andrews also worked with Milan Stojanović and Dr. Kyung-Ae Yang, both of Columbia, who were using nucleic acid receptors. Known as aptamers, these receptors have the benefit of being smaller than the bulkier protein receptors that previous research had focused on.

“Our breakthrough was that we used a different kind of receptor that was biologically inspired — after all, life began with RNA,” Andrews said. “This enabled us to overcome the salt-shield problem.”

In the new research, the team successfully identified and tested receptors for serotonin, dopamine, glucose and a lipid involved in cancer. The receptors were found to be selective and effective, even in brain tissue from mice.

The method can be used to study numerous types of molecules — to learn, for instance, how drugs change with time in the brain or other organs, how blood pressure is regulated or how signaling molecules associated with the gut microbiome ebb and flow.

Andrews’ main interest still lies in serotonin and its roles in psychiatric disorders like depression and anxiety.

“To develop dramatically better treatments, scientists need to understand how the human brain encodes information about anxiety or mood — processes that can go awry, sometimes with devastating consequences,” she said.

The team is now testing the strategy to measure neurochemicals in the brains of live animals.

The study’s other authors are Nako Nakatsuka, John Abendroth, Kevin Cheung, Xiaobin Xu, Hongyan Yang, Chuanzhen Zhao, Bowen Zhu and You Seung Rim, all of UCLA.

The research was supported by grants from the National Institutes of Health, the National Science Foundation, Cal-BRAIN, NantWorks, Hewlett-Packard, the Merkin Family Foundation and the China Scholarship Council.

Nakatsuka, Kyung-Ae Yang, Weiss, Stojanović, and Andrews have filed for a patent on stem-loop receptor-based field-effect sensor devices for sensing at physiological salt concentrations. Stojanović has patent applications pending and a startup company and earns consulting income for work on small-molecule aptamers.

Learn more about the neuroscience research theme at the David Geffen School of Medicine at UCLA.