Unraveling molecular basis of phytochemical accumulation toward improved human health - PROJECT SUMMARY/ABSTRACT The overarching goal of this AREA project is to uncover the genetic basis regulating soyasaponin accumulation for the development of value-increased crops to boost the human immune system and for alternative medicine. This project is urgent and significant to meet current and future unpredicted pandemics. Soyasaponins are a group of naturally occurring phytochemicals in legume species and has been reported to boost the human immune system. They also exhibit anti-viral, anti-cancer, and anti-diabetic activities. Previous research has been predominantly limited to examinations of soyasaponin's medicinal properties, but its biosynthetic pathway is not complete and little is known about its molecular determination in regulating soyasaponin accumulation. The lack of fundamental knowledge about these important bioactive compounds limits the success of plant metabolic engineering to develop soyasaponin-rich crops. The value-improved staple crops, such as soybean, can be consumed via a daily diet to boost immunity and can be made globally accessible to economically disadvantaged populations. This project is the first to bridge this critical gap and examine the molecular mechanisms regulating soyasaponin variation in natural plants applying interdisciplinary approaches, such as genomics, biochemistry, and CRISPR-Cas9 gene editing. The research goal will be accomplished by completion of the following two specific aims: 1) to identify candidate genes regulating soyasaponin production in wild soybeans, the wild progenitor of cultivated soybean with a large gene pool; and 2) to validate gene function of identified candidate genes in contributing to soyasaponin production using state-of-the-art CRISPR-Cas9 gene editing system. Our scientific contribution here is significant as it will address a crucial fundamental question of molecular basis regulating vital phytochemical production in natural plants. Specifically, our study will improve understanding of the molecular components and their functional relationships in soyasaponin production. Project results are expected to provide a significant step toward efficient plant metabolic engineering and/or molecular breeding to develop value-increased soybean cultivars to boost the human immune system through diet and ultimately lead to alternative strategies for the prevention and treatment of cancer and other chronic diseases. The mapping population and large genomic data will provide the plant community resource for deploying similar strategies to the study of other human health-related traits. This comprehensive research project will engage undergraduate and graduate students in a comprehensive interdisciplinary research environment. This AREA award will enhance the research environment at the University of North Carolina at Charlotte, a rapidly growing urban university with a large number of first-generation and low-income students. The PI has a strong track record of involving under-represented minorities and women in her research program. The final outcome of this interdisciplinary research project will create a broader impact on the improvement of public health, both locally and globally.