Mechanism and Manipulation of NLR-Mediated Immunity

About This Grant

Plants rely on a class of immune receptors known as nucleotide-binding leucine-rich repeat (NLR) proteins as one of their primary defenses against invading pathogens. However, this protection is often short-lived because pathogens can rapidly evolve to escape detection or suppress plant immune responses. This project focuses on the potato NLR protein RB, which provides broad-spectrum resistance against Phytophthora infestans, the pathogen responsible for late blight, a devastating disease that led to the Irish Potato Famine and still causes billions in losses worldwide. The research team will investigate how RB interacts with pathogen effector proteins and plant immune signaling components and how some pathogen strains evade this detection system. By integrating structural biology, biochemistry, and bioartificial intelligence (BIO-AI), the project aims to unravel complex host-pathogen interactions and design novel resistance traits. This work contributes to the growing bioeconomy by enabling more sustainable approaches to crop protection, reducing dependence on chemical pesticides, and helping farmers safeguard their yields through durable, genetically based resistance. Ultimately, the research advances our understanding of natural plant immunity, promoting agricultural resilience, food security, and environmental sustainability, while delivering significant benefits to both society and the economy. Plants utilize NLR immune receptors to detect pathogen effectors and initiate effector-triggered immunity (ETI). While substantial progress has been made in understanding how NLRs recognize effectors and trigger immune signaling, the molecular mechanisms by which pathogens evolve new effectors to suppress NLR function remain largely unknown. This project addresses this long-standing question by investigating how the potato NLR RB, which confers broad-spectrum resistance to Phytophthora infestans, recognizes its cognate effector and how this recognition is suppressed by a closely related virulence effector. By combining structural biology, biochemistry, and BIO-AI, the research will dissect the molecular mechanisms of effector recognition, NLR activation, downstream signaling, and effector-mediated suppression of ETI. These studies will advance fundamental knowledge of how NLRs mediate durable resistance across diverse pathogen strains and provide a rational framework for engineering immune receptors with expanded recognition specificity and improved durability in crops. 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.