Fostering diverse approaches to understanding brain function

Launching bold ideas

In 2014, the Carney Institute launched an innovation awards program to support early-stage research projects that are too new to attract external funding but have great potential to advance science and benefit society. The most recent gift will endow a similar innovation awards program, ensuring that the Carney Institute will be able to sustainably invest in innovation for years to come.

Ashley Webb—the Richard and Edna Salomon Assistant Professor of Molecular Biology, Cell Biology and Biochemistry at Brown—received an innovation award in 2019 to establish a new system to study how neurons age. She is developing a cell reprogramming platform, called “direct reprogramming,” to study aging in the hypothalamus brain region. The hypothalamus controls critical processes, such as sleep, temperature regulation, eating and metabolism, which can become dysregulated with aging. With direct reprogramming, Webb is able to convert a skin cell, for example, into a brain cell that maintains the hallmarks of aging.

“Aging is the greatest risk factor for a number of diseases, including neurodegenerative diseases such as Alzheimer’s,” Webb said. “If we understand what’s going wrong during aging, this will give us important insight into the mechanisms of disease. But right now, we don’t have very good systems for studying these diseases in the context of aging. This is the problem we are working to solve.”

Webb’s group started with mouse skin cells to generate rare hypothalamic brain cells. They are now applying the same approach to human cells, which for the first time will allow researchers to generate rare types of human neurons that are physiologically aged.

The Innovation Awards Program, Webb said, gave her group the freedom to take on a bold, early-stage idea. Her team hopes to use the direct reprogramming approach to generate neurons from individuals with brain diseases and disorders, such as Alzheimer’s.

“High-risk projects have the most potential to lead to breakthroughs in science and medicine, but funding mechanisms for this type of work are limited,” Webb said. “The Innovation Awards Program allowed us to pursue an exciting idea that wouldn’t have been funded by traditional funding mechanisms because they favor safe, well-established projects that often result in incremental advances.”

Gilad Barnea, director of the Center for the Neurobiology of Cells and Circuits at the Carney Institute, was an early recipient of an innovation award, which he said was critical to the success of his project. He developed “trans-Tango” technology to map functional brain circuits that control behaviors.

“The innovation award enabled us to cross the finish line with our work in the lab, so we could publish our findings in Neuron, one of the premier scientific journals in neuroscience,” he said.

Barnea’s published research — which was highly collaborative and involved undergraduate and graduate students as well as postdoctoral fellows — opens opportunities to study specific circuits and how they become abnormal in disease. Barnea has distributed the components of his system to many laboratories worldwide, and more than 100 papers have been published using “trans-Tango.” His group has secured external funding to continue to develop the technique to study the brain and to develop a similar technique to study cancer and the immune system.

Promoting computational brain science at Brown

A portion of the new $25 million gift will also be used to strengthen Brown’s leadership in the emerging field of computational neuroscience. Last summer, Brown established the Center for Computational Brain Science at the institute to harness the University’s expertise in computation, cognition and systems neuroscience.

“There have been a number of truly fabulous moments in Carney’s history, and the formation of the Center for Computational Brain Science is among the most meaningful,” Lipscombe said.

Computational neuroscience is a multidisciplinary field that seeks to understand the functions of the brain at all levels — from cells to cognition — using principles from physics, mathematics, engineering, computer science, biology, cognitive science and psychology. The center creates collaborations between basic brain science researchers and engineers, mathematicians and computer scientists, and brings computational neuroscience innovations to clinical applications and commercialization.

“The gift to computational brain science is incredibly impactful,” Lipscombe said. “It ensures that we are able to continue driving scientific discovery and supporting cutting-edge research that spans multiple fields of study.”

According to Michael Frank — director of the Center for Computational Brain Science and the recent recipient of the National Academy of Sciences’ Troland Award for early-career researchers — the gift is a statement of support, confidence, and appreciation for the contributions of computational neuroscientists at Brown.

“It will expand the scope with which brain scientists can leverage powerful computational methods to understand neural mechanisms of complex behavior; to learn from, and reciprocally inspire, development in artificial intelligence; and to facilitate translation to improve brain health,” he said.

This story was adapted from one that originally appeared on news.brown.edu.