Dissecting the functional link between immune signaling and defense-related autophagy

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By 2050, global food production needs to increase by 70% to feed the rapidly growing human population. Filamentous plant pathogens including oomycetes and fungi cause the most destructive crop diseases and pose a major threat to our food security. The late blight, caused by the Irish famine pathogen Phytophthora infestans, is a deadly disease of potato and tomato. Outbreaks caused by late blight, as well as the control measures undertaken to manage the disease, lead to more than £6 billion in annual losses globally. The management of the disease relies on costly agrochemicals some of which are under rigorous regulations due to environmental and health concerns. Reduced fungicide sensitivity in newly emerging strains worsen the situation. A sustainable alternative is to genetically improve resistance, a specific and targeted approach which requires a deeper understanding of plant immunity.Although plants have the genetic toolkit to fight diseases, the capacity of pathogens to adapt and evade plant immunity has constrained traditional resistance breeding. Plants defend against parasites through specialized immune sensors. Surface immune sensors, recognize molecules released by the parasites that are distinct from anything found in the plant. Activation of these surface receptors triggers immunity - known as pattern triggered immunity, or PTI. This kickstarts intricate signalling cascades that translate external immune stimuli into defense responses. The role of PTI in providing resistance to plant pathogens is well-established. However, the molecular mechanisms leading to enhanced resistance following PTI activation are not fully understood. Nevertheless, successful transfer of surface immune sensors from model plant species to crops has sparked renewed interest in understanding the innerworkings of PTI. Like other filamentous plant pathogens, the late blight pathogen invades host cells through finger-like extensions called haustoria, through which it secretes immunity-breaking factors to gain control of the invaded cells. Invaded plant cells often respond by concentrating their immune responses at the pathogen extensions to prevent further infection. Although PTI is implicated in the production of defense-compounds that are deployed towards the pathogen haustoria, the extent to which PTI regulates targeted cellular transport routes to the pathogen interface is not known. All plants and animals undergo a process of self-recycling called autophagy - this ensures that cellular components are degraded when necessary, while preserving the building-blocks, that can be reused in other cellular processes. Recently, ourselves and others discovered that autophagy is activated to contribute to defense against Phytophthora infestans, bacteria and viruses. We later discovered that defense-related autophagy machinery is diverted to pathogen interface to contribute to targeted immune responses. This pointed to more complex functions for autophagy than the widely known recycling roles. However, how defense-related autophagy pathways are activated and regulated at the molecular level, as well as the extent to which it is altered by PTI is unknown.In this proposal, we aim to characterize the molecular mechanisms that govern defense-related autophagy. We have generated substantial preliminary data that a regulator of defense-related autophagy machinery interacts with the PTI signaling components. Hence, we will specifically focus on investigating the molecular interplay between PTI and defense-related autophagy pathways to elucidate the molecular events leading to enhanced disease resistance. By decrypting these mechanisms, we will generate fundamental knowledge that will be helpful to remodel plant immune system towards improved pathogen resistance. This work will have far-reaching implications, as the defense-related autophagy machinery provides resistance to a diversity of important pathogens.