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Keriayn Smith, PhD, assistant professor in the Department of Genetics, was selected as one of six inaugural recipients of grants from the Hypothesis Fund to advance early-stage innovative research.

Keriayn Smith, PhD, assistant professor in the UNC Department of Genetics at the UNC School of Medicine, was selected among six scientists to receive an inaugural seed grant from the Hypothesis Fund, a new initiative dedicated to “advancing scientific knowledge by supporting early stage, innovative research that increases our adaptability against systemic risks to the health of people and the planet.”

Smith’s project, titled, “Not Junk: Noncoding RNAs as Determinants of Cell Identity,” was selected for the boldness of the science, her willingness to take risk and go after a big idea, and the potential long-term impact of her work.

The Hypothesis Fund takes a unique approach to supporting research. It empowers a diverse, world-class network of scientist scouts to identify the high-risk, high-reward ideas at the edge of the network that would otherwise be underfunded or not pursued at all.

The Hypothesis Fund, founded by David Sanford, supports research projects at their earliest stages, typically before there is any preliminary data. “Our funding is intended to be catalytic – a fast path to enable a scientist to ‘turn over the card’ and see what’s there,” Sanford said. “And we focus on bold new ideas in basic research, not continuations of existing research.”

Smith’s lab will use single cell/molecule and computational approaches to shed light on the importance of vastly understudied RNAs, to support a goal of defining roles for specific noncoding transcripts in developmental decisions in cells.

From Dr. Smith’s project abstract:

Most of the human genome does not directly code for protein important for specific functions inside cells. Less than 3% of the genome encodes messenger RNAs, and yet there is pervasive transcription to produce thousands of RNAs. This includes a myriad noncoding RNAs that are uncharacterized or understudied. The long noncoding RNA (lncRNA) class of RNAs are processed similar to mRNAs, and are thought to outnumber mRNAs in the human genome. While the field has grown exponentially over the past decade, only a small fraction of human lncRNAs (of ~20,000 human genes and ~60,000 transcripts) are well-understood.

However, the lncRNAs characterized experimentally thus far have important functions. These include influencing cellular processes such as transcription, splicing, and translation regulation, to impact cellular homeostasis and cell identity. Additionally, it is increasingly appreciated that many disease-causing SNPs are in noncoding regions of the genome that have the potential to produce lncRNAs. This, together with striking cell- and tissue-specific expression relative to mRNAs, suggests potential roles for lncRNAs in development and disease, including degenerative diseases and cancers.

“Our project will bring a new dimension to the vast body of ‘omics data by filling gaps that cannot be fully explained by bulk or protein-centric analyses,” Smith said. “Given the sheer numbers of lncRNAs, our project has the potential to add an entire dimension of knowledge to contribute to regenerative & personalized medicine approaches, including gene-therapy and theranostic development.

Along with Dr. Smith’s basic science interests she serves as the Director of Training & Excellence of the newly launched RNA Discovery Center at the UNC Lineberger Comprehensive Cancer Center, with a goal of increasing the diversity of scientists who study RNA. This is supported by a longstanding track-record of designing and executing programs that have impacted thousands of individuals at varying educational levels.

UNC School of Medicine Contact: Mark Derewicz