Soybean is an important legume crop that supplies more than half of the world’s vegetable oil and protein. Soybean cyst nematode (SCN) is the most damaging soybean pest worldwide, causing over $1.5 billion yearly yield loss in U.S. soybean production. Deploying SCN-resistant soybean varieties is the most efficient and environmentally friendly strategy for managing SCN damage. But this strategy is challenging because SCN populations evolve rapidly, and the current SCN-resistant soybean varieties are losing resistance. To solve this significant problem, the critical first steps are to identify new genetic resources with broad-spectrum SCN resistance and to uncover its underlying molecular mechanism. This project convenes an interdisciplinary group of researchers with expertise in various cutting-edge plant biology, including multi-omics, systems biology, functional genetics, plant physiology, phenotyping, and computational biology. The main objective is to uncover novel molecular mechanisms of broad nematode resistance in wild soybean (Glycine soja), the wild ancestor of cultivated soybeans. The results will inform the development of new soybean varieties with broad nematode resistance, which has a significant positive impact on agriculture and environmental sustainability in the U.S. and the world. This research will also provide opportunities to train omics-enabled plant biologists and high-school teachers.<br/><br/>This project will leverage the newly identified wild soybean (Glycine soja) genotype with broad-spectrum soybean cyst nematode (SCN) resistance to unravel the molecular mechanisms underlying its broad resistance. Preliminary studies showed that the well-known mechanisms in the current soybean cultivars could not explain the wild soybean resistance, indicating novel mechanisms for defending against SCN. Rather than targeting a single well-studied SCN type, this innovative research will focus on multiple less-studied, but widespread SCN types. This is the first study to dissect the novel mechanisms of broad SCN resistance in wild soybean through integrating population genomics, multi-omics, systems analyses, and genome editing. The results will deepen our understanding of the molecular mechanisms underlying plant nematode defense and inform the development of soybean varieties with broad-spectrum nematode resistance. Additionally, we will use this study to showcase the utility of crop wild relatives, evolutionary principles, and systems biology tool-kit in improving crops for stress resilience and increased yield.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.