The National Institutes of Health (NIH) has awarded grants to three University of Utah Health scientists through its competitive High-Risk, High-Reward Research (HRHR) program that funds highly innovative and unusually impactful biomedical or behavioral research proposed by extraordinarily creative scientists.
Justin English, Ph.D., assistant professor of biochemistry; Jim Heys, Ph.D., assistant professor of neurobiology; and Stefano Brigidi, Ph.D., assistant professor of neurobiology are among 64 recipients of the 2021 NIH Director’s New Innovator Award. The award, funded by HRHR Program, supports unusually innovative research by early career scientific investigators.
I extend my heartiest congratulations to Drs. Brigidi, Heys, and English. Discovery and innovation are foundational elements for advancing human health. The creativity of these talented scientists is exciting to see and exemplifies the high-quality research at U of U Health.“
Willard Dere, M.D., associate vice president for research, U of U Health
The three U of U Health projects will explore the molecular underpinnings of how the world shapes us.
Discovering how our cells interpret their world –– Justin English, Ph.D.
The cells in our body have receptor proteins. These receptors act like radios, converting signals they receive into instructions our cells can understand. Every cell in our body contains thousands of these receptors, each tuned to a different station, producing a cacophony of instructions. Determining which instructions result in good health or disease requires that we change the volume of a receptor, a feat we have been unable to accomplish until now.
English engineers the tools necessary to control the volume of individual receptors. In doing so, he aims to determine which are important for specific biological processes. Leveraging his new method to evolve engineered proteins, he is creating light-activated tools to stimulate or inhibit specific receptors. By adjusting the volume of specific receptors, he seeks to understand, “how receptors make us who we are.”
Connecting time and memory –– Jim Heys, Ph.D.
Imagine driving to work during rush hour. One route takes about an hour. Another route, which is less direct and involves driving farther, only takes 40 minutes. Which do you choose and why? It all comes down to internal clocks in the brain and the role they play bundling time, place, and experience into memories, according to Heys. In particular, he is trying to determine where these clocks are in the brain and how they interact with areas in the brain that keep track of where we are.
Understanding how the brain keeps track of time is one of the biggest mysteries in neuroscience. Based on earlier research, Heys theorizes that some brain circuitry in the prefrontal cortex is organized as universal clocks. In tandem, he suspects that a structure called the medial entorhinal cortex could have a key role in interpreting information collected by these clocks and linking the timing of events recorded in the prefrontal cortex to other structures in the brain that keep track of places or experiences in our lives. The tools developed in Heys’ lab allow scientists to observe the activity of thousands of individual neurons simultaneously as animals perform tasks. It will also allow them to learn more about how memories of space and time are formed. Support provided by his NIH award will allow Heys to expand this research.
How experience shapes memory and behavior –– Stefano Brigidi, Ph.D.
Whether it’s the birth of a child or a promotion at work, the most significant experiences of our daily lives stand out and guide our memories and behaviors. Experiences are transformed by the brain into patterns of electrical activity distributed across its circuitry composed of neurons and synapses. But how do our most important experiences and the activity of neurons shape our learning at the molecular level? Brigidi believes the answer lies in the cellular nuclei of neurons, where our experiences and genes intersect.
Transcription factors are proteins that bind DNA within genes and guide when and where those genes are expressed. With this award, Brigidi will be testing whether transcription factors activated by novel sensory experiences trigger specific patterns of gene expression that shape brain synapses and circuits in predictable ways. The research will help understand how past experiences influence our responses in the present and in the future.
These three projects and others nationwide showcase the spirit of the High-Risk High-Reward program, which encourages scientists to think “outside the box” and pursue trailblazing ideas that advance knowledge and enhance health.
“The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known,” says NIH Director Francis S. Collins, M.D., Ph.D., “These visionary investigators come from a wide breadth of career stages and show that groundbreaking science can happen at any career level given the right opportunity."
In addition to the 64 New Innovator awards, the NIH issued 10 Pioneer awards, 19 Transformative Research awards, and 13 Early Independence awards.
The High-Risk, High-Reward Research Program is part of the NIH Common Fund, which oversees programs that pursue major opportunities and gaps throughout the research enterprise that are of great importance to NIH and require collaboration across the agency to succeed.