ENSA researchers at Aarhus University have identified how two molecular changes can shift the native program of plants from defending themselves against harmful microbes to collaborating with nitrogen-fixing bacteria. This discovery brings major crops one step closer to thriving without synthetic fertilizer. The multidisciplinary research project was driven by first authors Magdalini Tsitsikli (now at the University of Freiburg), Bine Simonsen, and Thi-Bich Luu in the groups of Simona Radutoiu and Kasper Røjkjær Andersen. The research was published in Nature in November 2025.
The power of microbes
Plants depend on nitrogen to grow, yet only legumes like peas and beans can form a natural symbiosis with rhizobia bacteria that make atmospheric nitrogen available to them. That means that most crops rely on chemical fertilizers. But these are energy-intensive to produce, emit large amounts of CO₂, and remain unaffordable for many smallholder farmers.
That’s why ENSA scientists are researching how this symbiosis occurs in legumes, with the vision of transferring this ability to crop plants like maize and cassava, helping create nitrogen-efficient varieties that support more sustainable and equitable farming worldwide.
“We are improving crops that will help the environment – and help humanity.”
Magdalini Tsitsikli
“If we can extend this symbiosis to the crops we eat most, it will fundamentally shape the way we do agriculture today,” says ENSA Scientific Director and group leader Simona Radutoiu. These benefits are clear to the researchers in the lab too. “We are improving crops that will help the environment – and help humanity,” says Magdalini. Such a shift would reduce CO₂ emissions, lower fertilizer costs, and help close yield gaps in regions where food security depends most on affordable, sustainable solutions.
“Small changes that make a huge difference”
The team revealed that just two amino acids within a receptor protein determine whether a plant defends itself by activating its immune system or if it “opens the door” to collaborate with symbiotic bacteria. Using a combination of molecular genetics, structural biology and inventive protein engineering, the researchers reached down to these two amino acids located in the Symbiosis Determinant 1, a small area in the intracellular region of receptor protein.
This minimal change allowed the team to reprogram legume and barley receptors that usually activate the immune system, into receptor versions that allow symbiosis with bacteria. When they introduced the reprogrammed receptors into a non-symbiotic version of the legume Lotus japonicus, nitrogen fixation worked again. “Our discovery revealed the smallest changes needed to reprogram molecules for symbiosis,” says Bich. “Small changes that make a huge difference – that’s the exciting part.”
Teamwork and ambition
The discovery emerged from intensive teamwork, and for the scientists involved, the experience was deeply motivating. “With experimental science, things can often go wrong, so when you finally get a structure or you compare notes with colleagues and see the connections forming, you really get a sense of achievement,” says Bine. “It’s a privilege to be in a lab that’s so ambitious and has such a big outlook.” This perspective is shared by Magdalini and continues beyond the lab, to the overarching ENSA project. “It’s fascinating to be part of ENSA,” she says. “It’s an amazing network of people that you can brainstorm with across fields.”
The project was made possible thanks to funding and long-term strategic support from Gates Agricultural Innovations (Gates Ag One) and the Novo Nordisk Foundation.
Read the full paper here.
Photos from left to right: Magdalini Tsitsikli, Bine Simonsen, and Thi-Bich Luu.
Photo credits: Magdalini Tsitsikli, Bine Simonsen, and Emma Steer
Text: Emma Steer