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New national research hub takes shape at Brown

With $9.2 million in funding from the National Science Foundation, the NeuroNex Technology Hub will promote national access to an innovative neuroscience platform tool, bioluminescent optogenetics

Photo by Nathan Shaner, courtesy of Brown University

The four tubes displayed contain the ingredients that produce bioluminescence: Coelenterazine appears buoyant, swirling as it interacts with luciferase. The three tubes on the right also contain different colored fluorescent proteins attached to the luciferase which, as a result, emit cyan, green or yellow light

By Richard Asinof
Posted 8/7/17
A new national research hub at Brown, funded with $9.2 million from the National Science Foundation, seeks to spread access to the techniques and technology around bioluminescent optogenetics and its promising potential to drive future brain research.
How does the model of the new research hub, promoting open access to data and resources and technology, challenge the existing paradigm around competitive research platforms and venture capital investment? Are there opportunities for collaboration with the work being done through immuno-informatic tools by EpiVax? Beyond Parkinsons and epilepsy, what opportunities exist to research ways for the brain to restore its own balance around the cascading of cortisol in toxic stress and in cravings for opiates in receptors tied to substance use disorders? With the creation of a national research hub at Brown around bioluminescent optogenetics, how does that fit into the viability of leveraging that as a potential innovation hub in Rhode Island?
A primary focus of the NeuroNex Technology Hub is to build a new science curriculum for grade-school students, offering an interconnected educational platform for biology, chemistry, physics, and neuroscience. More than, say, an emphasis on coding, the new science curriculum provides a way to teach students scientific skills that connect theory with a tangible, interactive visual representation, one that celebrates biodiversity and biological evolution, connecting with the natural world we all live in. The innovative curriculum has the potential to go viral, as they say. How quickly will schools in Rhode Island adopt the curriculum to complement the efforts around coding?

PROVIDENCE – The award of a new $9.2 million grant by the National Science Foundation to Brown University to serve as a national hub to develop and to promote the next generation of neuroscience research tools using bioluminescent optogenetics represents something much more than a traditional research grant, according to Christopher Moore, the principal investigator, a professor of Neuroscience at Brown University and an associate director at the Brown Institute for Brain Science.

“It is more of a cooperative collaboration with the National Science Foundation to make this venture happen,” Moore explained in a recent interview with ConvergenceRI, describing the innovative approach of the award announced on Aug. 1.

The mission of the new five-year initiative, Moore continued, is to create access to these “exciting, cutting-edge” new research tools through a national research hub – and to further science education at both the university and the grade school level.

The new venture focuses on the development of bioluminescent optogenetics, or BL-OG – what Moore described in a 2015 interview with ConvergenceRI as a new “platform tool” in neuroscience research – the capability to illuminate biologic processes with precision without invasive procedures. [See link below to the ConvergenceRI story, “Programming brain cells to turn their own light on and off like a firefly.”]

“About 15 years ago, optogenetics emerged, engineering brain cells, making them sensitive to light, and studying how the cells changed in relationship to some action, or perception, such as remembering your phone number,” Moore said during the 2015 interview.

“That was a huge advance. With BL-OG, one of the things you don’t need to do is to put an [invasive optic implant] in the brain. We’ll be producing light with this method, not imaging that light to show what the brain is doing, but controlling what the brain is doing.”

The new national research hub, what is to be called the “NeuroNex Technology Hub,” is actually a collaborative venture involving three neuroscience labs – at Brown, at Central Michigan University, and at the Scintillon Institute in San Diego, Calif.

The four principal investigators include: Moore; Diane Lipscombe, professor of Neuroscience at Brown and director of BIBS; Ute Hochgeschwender at Central Michigan University, and Nathan Shaner at Scintillon.

The new hub builds upon the work Moore and his colleagues have pursued in bioluminescent optogenetics that had been funded with a $1 million, three-year grant from the W. M. Keck Foundation

“Our job in the new venture,” the NeuroNex Technology Hub, Moore told ConvergenceRI in an interview conducted last week, is to innovate in the BL-OG technology and push the cutting-edge methods forward.

“Half to two-thirds of the effort is to make sure that anyone who would like to know how to use [the technology] can gain access to it,” Moore said, describing it as an investment in science equity, in support of the open science movement.

Moore, calling himself a believer and a participant in the open science movement, said it was “an attempt to remove the barriers to research, addressing a social need to level the playing field, to share data and resources in a way to rapidly accelerate the rate of discovery.”

A third aspect of the new collaboration with the National Science Foundation is to use bioluminescent optogenetics in what Moore called “a fantastic opportunity” to teach science at the grade school level, developing a new curriculum.

Bioluminescence, Moore explained, is a kind of pure evolutionary biology, involved in attracting mates and stalking prey. “A majority of sea creatures have bioluminescent [capabilities],” Moore said, enabling a curriculum that can explore how life transfers through water.

The curriculum will offer opportunities for compelling lessons in biology, chemistry, physics and neuroscience.

The effort to create a new science curriculum involves collaboration with the ongoing work of students involved with the Brown Brain Bee, teaching courses in local Providence high schools. The goal is to create an online version of the curriculum that can be shared with other schools nationwide.

Here is the ConvergenceRI interview with Christopher Moore, one of the principal investigators at Brown who will be fashioning the NeuroNex Technology Hub as a national neuroscience research hub under a new $9.2 million award from the National Science Foundation, with the goal of creating access and training on how to use bioluminescent optogenetics.

ConvergenceRI: How does the new research hub build upon your ongoing work on bioluminescent optogenetics that was funded through the $1 million, three-year grant from the W.M. Keck Foundation?
That is the perfect question. We have been working at building the tools and expanding the skills scope of what we’re trying to achieve – not just controlling cells but imaging them, with a big emphasis on training and technique.

In the past marine biological labs had identified fluctuations in relationship to calcium in cells in quorum sensing [signaling molecules] in jellyfish – it flashed light when it interacted with calcium.

Calcium fluctuations are a good indicator of neuronal [activities and] changes. Researchers want to create [a more precise mechanism] to image the complexity of the way that calcium ion [channels] work in animals, in how the brain works, at the cellular level.

The potential for using bioluminescent optogenetics to image calcium ion interactions is enormous.

ConvergenceRI: What is the mission of the NeuroNex Technology Hub?
A major emphasis is on having the same [clarity of] resolution in brain science that has happened in the space program and in molecular biology.

The hub is a way to invest in providing access to the cutting-edge techniques, to create innovations in the technology, and to push the methods forward.

Half to two-thirds of the investment is targeted to make sure that anyone who would like to know how to use [bioluminescent optogenetics] can get that information. It’s really about investing in equity.

It is part of the open science movement, of which I am a believer in and a participant in – the notion of what it means to share data, resources and technology in an open way to rapidly accelerate the rate of discovery.

It addresses a social need to level the playing field; it is literally an attempt to remove the barriers to research. It is really wonderful and exciting.

ConvergenceRI: Why is it important to build access to these new tools? How important is collaboration and not competition as part of neuroscience research? How does that play out at Brown?
The hub is not just at Brown; the team of four principal investigators include Ute Hochgeschwender at Central Michigan University and Nathan Shaner at Scintillon Institute in San Diego.

One of the key things in the grant is to enable anyone who is interested in learning these methods to come to Brown and attend daylong workshops in imaging and the techniques of bioluminescent technology.

To meet with people, talk with other researchers, develop a personal relationship, and providing hands-on training for people to learn how to do this stuff.

That kind of experience is much more valuable that publishing a paper; the information gets transmitted a lot more quickly, if you can talk to someone and figure out how to do something. There is no substitute for personal interactions in science.

Another part of the hub is that there will be emissaries – grad students and post-docs – to go out to other neuroscience labs. They will get to be seen as experts, building their own networks. The cooperative collaboration is focused on developing a national research resource to promote the tools, reaching out to any lab, and to cultivate interest, with a comprehensive website.

A third aspect of the grant, one that I love, is that we’re going to create an educational curriculum targeted to grade school kids. Bioluminescence creates fantastic opportunities to teach science in a compelling fashion.

It’s about pure evolutionary biology; exploring why it evolved in the history of evolution, in attracting mates, in stalking prey. A majority of sea creatures are bioluminescent; [allowing you] to explore how life transfers through water.

It involves lessons in biology, physics, chemistry – and neuroscience, exploring why neuroscience is tracking calcium interactions.

ConvergenceRI: In terms of clinical translational research potential, are there any particular low-hanging fruit that is envisioned as a potential target? In the past, you have mentioned epilepsy, and the potential to control the way that the brain can send signals to control the onset of waves of activities leading to a seizure.
I think the next generation of tools to treat brain disorders, instead of imposing some constant control [through drugs], will seek to allow the brain to do its own thing, to help nudge it back toward its normal state when it starts to deviate, to let its own dynamics evolve.

For instance, in detecting a seizure, allow the brain to drive itself back into a normal state of function.

With bioluminescent optogenetics, in general, we are part of a much broader trend about how to treat diseases and disorders. In cancer treatments, for instance, a lot of the ongoing work is in stimulating the body’s own immune system and bring it back to health.

I think that is exactly where brain treatments need to go – to leverage the body’s own recognition dynamic and tipping it back into focus – that somehow the dynamics have gone wrong and attempting to put them back into place.

ConvergenceRI: In terms of tools for research, are there, in a similar fashion, particular ways that the bioluminescent optogenetics could be targeted?
There was some excitement a while ago that bioluminescence might serve as a kind of useful toxicity to burn cells, zapping them with light. To my knowledge, it did not produce any results.

In other words, with bioluminescence, there is now growing recognition about how biocompatible it is, looking through the lens of evolution.

The short answer is that there are a couple of ideas that we’re looking at, in regard to other cell processes, with more imaging, and the potential to trigger those sensor to trigger other cell processes. There is a lot of ambiguity. It’s not something that translates easily from the whiteboard to functionality in the lab.


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