Engineered tandem kinase receptors bound two blast effectors in wheat protoplasts

Magnaporthe oryzae infects by inserting effector proteins into leaf and stem cells, where they manipulate the host and promote disease ^[5]. Some cereal receptors carry an integrated heavy metal-associated domain. The John Innes Centre group reports that the HMA acts as a biological bait, luring effectors into binding ^[12]. Recognition then triggers an immune response that kills cells locally to limit the pathogen's spread ^[6].

"If we can engineer these integrated HMA domains for new properties by making amino acid protein changes where effectors bind, we can gain what we call novel recognition specificities," Banfield said ^[10]. Biophysical analysis and crystallography gave the group a high-resolution picture of the HMA-effector interaction ^[11]. They used that picture to build tandem kinase protein receptors with dual specificity, binding effectors associated with infection of both wheat and barley. The study reports that such dual binding does not happen often in nature ^[13].

The readout came from protoplasts, individual wheat cells serving as surrogates for whole plant tissue ^[14]. A single cell can show that a receptor bound its target and fired. Lesion spread across a leaf, and the cost to the plant of carrying the engineered receptor, sit outside that readout. Translating the surrogate assays to greenhouse plants is the group's stated next step ^[14].

The report makes its argument about the tools available for receptor engineering, and does not compare this route with fungicide use ^[19]. Those tools have a 30-year head start on one class and almost none on the other: NLR receptors have been the focus of a considerable body of research for more than three decades ^[7], while TKPs were described in cereals only recently ^[8]. The claim from the authors is that the older methods carry across.

"Our study indicates that this new class of resistance proteins is amenable for engineering purposes. We now know that the previous tools we used in engineering NLR receptors may also work with this new class," said Daniel Yu, the study's first author ^[15]. The paper also points to precision breeding and AI approaches as ways to build novel specificity into HMA domains ^[18].

The longer-range idea is to use both receptor classes at once. "We think these two classes of immune receptors, NLRs and TKPs, are probably activated in different ways," Banfield said, and he described stacking genes encoding TKPs and NLRs against the same disease as a route to a super-resistant crop ^[16][17]. If the two classes are activated differently, a pathogen that escapes one recognition event still has to escape the other. Field isolates are the test: the fungus causes the most serious disease of cultivated rice, and has already reached wheat and barley in parts of Asia and Africa ^[4].