Xuan Zhuang, assistant professor of biological sciences in the Fulbright College of Arts and Sciences, was recently awarded a $436,000 National Institutes of Health R15 grant, titled "Dissecting cryptic genetic variation underlying complex traits in Drosophila." This award will provide three years of independent research funding in support of Zhuang's work.

The Zhuang Lab's research focuses on understanding the genetic basis of complex trait variation and novel trait evolution, involving the genetic architecture of complex diseases, the origination of genetic novelty and diversity, and the underlying molecular mechanisms. Employing molecular evolution, quantitative genetics, genomics, and bioinformatics, the research group conducts studies on both model organisms, such as fruit flies, and non-model organisms, such as polar fishes.

"In genetics, there is something interesting called 'cryptic genetic variation.' It is hidden genetic potential that does not show itself under normal circumstances; however, it can cause disease when the right combination of genes and environment comes into play. It is like a puzzle waiting to be solved," said Zhuang. "We use fruit flies (Drosophila) as our experimental model. They are great for this kind of research because they have loads of genetic diversity, and we can easily adjust their genes and environment within a relatively short timeframe."

The awarded project aims to unveil cryptic genetic variation, understand how genes interact with each other and the environment to influence metabolism and development, and introduce innovative models and strategies for investigating complex traits. To uncover cryptic genetic variation, the Zhuang Lab performs research in two ways.  First, they manipulate genes using an 'inducible genetic defect' — like flipping a genetic switch. Second, they increase stress with a high-sugar diet — an environmental factor that can have a significant impact on the metabolism. The project will employ multiomic approaches to investigate effects on the genes themselves (i.e., genomics), the messages they send (i.e., transcriptomics), and even the chemicals they produce (i.e., metabolomics). "By doing this, we will piece together how genes talk to each other and how they respond to their environment, all while influencing metabolism and development," said Zhuang.  

Zhuang's initial research that led to this NIH award was supported by the Arkansas Integrative Metabolic Research Center (AIMRC), funded through an NIH P20 COBRE award (P20GM139768). Zhuang was awarded pilot project awards from the AIMRC in 2021 to develop an inducible Drosophila model of insulin deficiency, and in 2022 to investigate high sugar diet-induced diabetic-like traits in Drosophila.

As an AIMRC pilot project awardee, researchers like Zhuang benefit from funding to support the collection of preliminary data that can be used to apply for federal research grants. They also receive technical support from the AIMRC's Imaging and Spectroscopy Core, Bioenergetics Core, and Data Science Core as needed, and participate in the weekly seminar series, and annual symposium organized by the AIMRC. Of note, the Data Science Core will assist Zhuang in developing novel algorithms and quantitative analysis pipelines for large -omic datasets generated through her new R15 grant. Like other center members, Zhuang also took advantage of proposal development support from the AIMRC, which was helpful in preparing a competitive NIH grant submission.

For more information on becoming an AIMRC pilot project awardee, project leader, or for other AIMRC funding and collaborative opportunities, please visit the center website at aimrc.uark.edu or contact Kimberley Fuller at fullerk@uark.edu for more information.