The National Institutes of Health awarded Xuan Zhuang, an assistant professor of biological sciences at the University of Arkansas, about $2 million to study how genes and the environment work together to impact health. Of specific interest is how differences in genetic background can influence susceptibility to metabolic diseases, such as Type 2 diabetes, through differences in diet.

"Every person's traits — like his or her metabolism or susceptibility to disease — are shaped by a mix of genes and the environment," Zhuang explains. "Some genetic differences don't show an effect under normal conditions, but when the environment changes, their impact becomes clear. By understanding these hidden genetic effects, we can better understand disease risk and resilience."

This research could uncover hidden genetic variation, unknown gene-trait connections and gene-environment interactions, ultimately improving our understanding of complex diseases and paving the way for more approaches to precise medicine.

Zhuang will use fruit flies as a model species to study these incredibly complex interactions. She and her team will use both large, outbred fly populations, which mimic human populations with diverse genetic backgrounds, and inbred fly populations, where all individuals within a strain share the same genome, to carefully test the effects of different environments. They will be fed different diets, such as high sugar or high fat, to study how genes interact with dietary changes to influence traits related to metabolism, development and physiology.

She notes that some flies can be fed a high sugar diet and have a high blood sugar level while others on the same diet do not experience the same impact on blood sugar levels. The question is whether something in their genetic makeup makes them more tolerant of increased sugar levels and prevents the expression of disease.

The goal is to identify and map out candidate genes that play an outsized role in disease-related traits response to differences in diet. Hundreds, if not thousands, of genes may be involved in a trait (what's known as polygeny) while a single gene can affect multiple traits (called pleiotropy). Adding environmental factors to that mix makes for extremely complex interactions. Ideally, the results of this study will translate to the study of human diseases once the mechanism by which certain diets trigger certain genetic responses is better understood.

By combining these approaches with a multi-omic strategy — integrating data from DNA, RNA, proteins, metabolites and other molecules — the team aims to build a comprehensive map linking genes, molecular activity and traits.

Zhuang was a Research Project Leader (or RPL) in the Arkansas Integrative Metabolic Research Center (or AIMRC), and with the receipt of this award, she will "graduate" from the RPL program. In this role, she received funding to generate preliminary data; gained access to AIMRC's Imaging and Spectroscopy, Bioenergetics and Data Science Cores for technical support; and participated in mentoring and scientific exchange through seminars, meetings and the annual symposium. She also benefited from proposal development assistance, which directly contributed to the strength of her NIH grant application.

The AIMRC was founded in 2021 by Kyle Quinn with support from the university and an NIH Centers of Biomedical Research Excellence award. The AIMRC is now led by Narasimhan Rajaram, a professor of biomedical engineering, who became its director in the summer of 2025.

"Dr. Zhuang is working on cutting-edge basic science research that can help us understand, and hence better treat, metabolic diseases that affect thousands of Arkansans each year. The AIMRC is excited to work with Dr. Zhuang in helping her accomplish the goals of her project," Rajaram said.

Reflecting on her experience, Zhuang said that "Serving as an AIMRC Research Project Leader provided me with seed funding, access to core facilities and structured mentoring that were critical in building a solid foundation of preliminary data and in sharpening my ability to craft competitive proposals. These experiences directly informed my current grant submission and have been integral to my development as a professor."

By combining technical expertise and providing access to advanced equipment in the three core areas, along with a cross-disciplinary faculty development and mentoring program, the AIMRC aims to foster a cohort of independent researchers with federally funded projects related to metabolism.