Engineering CC-HMA-NLR immune receptors for disease resistance in crops (ERiC)
Lead Research Organisation:
University of East Anglia
Department Name: Biological Sciences
Abstract
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Technical Summary
Engineering the plant immune system provides opportunities to develop novel genetic approaches to disease resistance in key crops that feed the world. In previous work, we determined the molecular details of how integrated HMA domains in the rice paired NLRs Pik-1/Pik-2 recognise different alleles of the rice blast pathogen effector AVR-Pik. This work demonstrated the potential of conferring enhanced resistance to plant diseases by engineering increased binding strength between NLR-IDs and pathogen effectors. This proof-of-principle study has paved the way for the work proposed here, to generate chimeric CC-HMA-NLRs with bespoke domains that detect divergent, widely distributed effectors from across host-specific pathogen lineages. This is important as different M. oryzae lineages infect different cereal crops. The research performed here will inform approaches to address epidemics of diseases such as wheat blast, which has recently emerged in Asia and Africa.
To deliver our objectives we propose a multi-disciplinary approach combining biochemistry, structural biology, genetics and plant pathology. Building on our preliminary data, we will first determine the extent to which cereal HMA proteins bind variants of the M. oryzae PWL effector family to understand specificity and identify targets for CC-HMA-NLR engineering. We will then use in vitro and in planta assays to optimise the binding of these HMA domains to PWL effectors, including incorporating into the CC-HMA-NLR scaffold (the latter will also allow monitoring of immune responses). Further, we will develop the Pik-1/Pik-2 system outside the HMA domain to deliver optimal immune responses. Finally, we will transform rice, barley and wheat cultivars with engineered CC-HMA-NLRs and test for resistance against both Lab strains of M. oryzae with different PWL effector complements and natural isolates collected from disease outbreaks.
To deliver our objectives we propose a multi-disciplinary approach combining biochemistry, structural biology, genetics and plant pathology. Building on our preliminary data, we will first determine the extent to which cereal HMA proteins bind variants of the M. oryzae PWL effector family to understand specificity and identify targets for CC-HMA-NLR engineering. We will then use in vitro and in planta assays to optimise the binding of these HMA domains to PWL effectors, including incorporating into the CC-HMA-NLR scaffold (the latter will also allow monitoring of immune responses). Further, we will develop the Pik-1/Pik-2 system outside the HMA domain to deliver optimal immune responses. Finally, we will transform rice, barley and wheat cultivars with engineered CC-HMA-NLRs and test for resistance against both Lab strains of M. oryzae with different PWL effector complements and natural isolates collected from disease outbreaks.
Organisations
- University of East Anglia (Lead Research Organisation)
- Wageningen University & Research (Collaboration)
- Bangabandhu Sheikh Mujibur Rahman Agricultural University (Collaboration)
- International Centre for Maize and Wheat Improvement (CIMMYT) (Collaboration)
- Nanjing Agricultural University (Collaboration)
People |
ORCID iD |
| Sophien Kamoun (Principal Investigator) |
Publications
Adachi H
(2023)
An atypical NLR protein modulates the NRC immune receptor network in Nicotiana benthamiana.
in PLoS genetics
Adachi H
(2022)
NLR receptor networks in plants.
in Essays in biochemistry
Adachi H
(2023)
The ancient guardian: ZAR1 evolutionary journey and adaptations
Adachi H
(2022)
NLR receptor networks in plants
Adachi H
(2022)
NLR receptor networks in plants
Adachi H
(2023)
The ancient guardian: ZAR1 evolutionary journey and adaptations
Adachi H
(2023)
Jurassic NLR: Conserved and dynamic evolutionary features of the atypically ancient immune receptor ZAR1.
in The Plant cell
Ahn HK
(2023)
Effector-dependent activation and oligomerization of plant NRC class helper NLRs by sensor NLR immune receptors Rpi-amr3 and Rpi-amr1.
in The EMBO journal
AmirAli Toghani
(2024)
PREreview of "A wheat tandem kinase sensor activates an NLR helper to trigger immunity"
| Description | Scientists have made significant progress in enhancing plants' ability to fight off diseases, which is crucial for protecting our global food supply. The team focused on a specific rice immune receptor called Pik-1, which is part of the plant's defense system against diseases, specifically one caused by a fungus that affects various hosts. Typically, plant pathogens evolve quickly, which can make engineered resistance traits less effective over time. The innovation here is that researchers successfully modified the Pik-1 receptor so it could detect a common threat from a widespread fungus, thereby broadening the rice plant's defense mechanism. They achieved this by swapping out a part of the Pik-1 receptor with a piece from another protein that the fungus commonly targets. This new, engineered receptor could recognize and respond to a broader range of threats from different strains of the fungus. By examining the structure of how the new receptor part interacts with the fungus, the scientists discovered that their engineered receptor forms a strong and complex bond with the fungus, which is not easily broken or bypassed by the pathogen. This suggests that the modified plant immune receptor might offer long-lasting protection against the fungus in real-world agricultural settings. Overall, this work is a step forward in creating more resilient plants that can fend off diseases, which is vital for ensuring stable food supplies in the face of various plant pathogens. |
| Exploitation Route | By applying the findings of this research, agricultural scientists and biotechnologists can develop new crop varieties with enhanced resistance to a range of pathogens, potentially increasing yield stability and reducing reliance on chemical pesticides. The findings can be incorporated into academic curricula and professional training programs, fostering a new generation of scientists equipped with cutting-edge techniques in plant biology and bioengineering. The project may foster collaborations across disciplines, bringing together experts in genetics, biochemistry, agriculture, and beyond to tackle complex challenges in plant science and crop protection. |
| Sectors | Agriculture Food and Drink Education Manufacturing including Industrial Biotechology |
| URL | https://doi.org/10.1101/2024.01.20.576400 |
| Description | Collaboration with Prof. Suomeng Dong |
| Organisation | Nanjing Agricultural University |
| Country | China |
| Sector | Academic/University |
| PI Contribution | Transcriptome specialization following host-jumps in the Irish potato famine pathogen lineage The collaborator Prof. Kamoun is a world leading scientist in the field of plant-microbe interactions. Short visits of young Chinese scientists to Prof. Kamoun's group at The Sainsbury Lab to carry out collaboration will greatly enhance their career development by exposure to an outstanding research environment and cutting edge scientific research. Among the benefits, the visiting scientists will enhance their communication and presentation skills by joining weekly lab meetings and presenting their own work. Overall, these activities will help foster the next generation scientists of China and enable them to build lasting connections with UK science. More specifically, Chinese research community will access high-quality and large-scale PacBio sequencing of potato late blight genomes. The CRISPR/Cas9 tool that modified in this project will be shared with the wider Chinese Phytopathology community. Also, the open source aspects of the project would serve as an exemplar for the wider community. China is the biggest potato producer in the world yet late blight remains the number disease and problem of the Chinese potato crop. This project would ultimately provide useful information for engineering |
| Collaborator Contribution | Nanjing Agricultural University (NAU) is the center of excellence for oomycete (Phytophthora) research in China. After joining NAU in 2014, Prof. Suomeng Dong has quickly developed into one of the most energetic new wave scientists in this field, having studied several aspects of Phytophthora gene regulation, such as discovering m6A DNA methylation and alternative splicing pathways. He received prestigious awards such as Chinese National Science Fund for Excellent Young investigator and National Thousand Youth Talents Plan. Thus, the UK team would greatly benefit from the collaboration not only from an intellectual perspective but also from the practical aspects of technology transfer, method development and exchange of biomaterial. Visits to China would be extremely productive as they will tap into years of experience with Phytophthora, notably CRISPR/Cas gene editing. The collaboration would not only benefit the Kamoun Lab but also other groups at TSL that have an interest in P. infestans, e.g. the groups of Jonathan Jones and Wenbo Ma. This project will also strengthen links between the Norwich and China, given Centre of Excellence for Plant and Microbial Science (CEPAMS)-a budding partnership between the Norwich based John Innes Centre and the Chinese Academy of Sciences (CAS). |
| Impact | 11 joint publications per PubMed (March 2021) https://pubmed.ncbi.nlm.nih.gov/?term=kamoun+AND+dong |
| Start Year | 2012 |
| Description | Collaboration with Prof. Tofazzal Islam |
| Organisation | Bangabandhu Sheikh Mujibur Rahman Agricultural University |
| Country | Bangladesh |
| Sector | Academic/University |
| PI Contribution | Exchange of materials/expertise. |
| Collaborator Contribution | Exchange of materials/expertise. Professor Islam's group is working on genomic and postgenomic analyses of wheat blast fungus, which recently emerged as a devastating pathogen of wheat in Bangladesh. He is leading a dream project titled "Mining biogold from Bangladesh"where they identified more than 600 plant probiotics potential for using as biofertilizer and biopesticides. Another important focus of Prof. Islam's group is to analyze the genomes of a number of plant probiotic bacteria potential for biocontrol of major phytopathogens and biofertilization of rice and wheat. In collaboration with Prof. Sophien Kamoun, Prof. Islam is dedicated to the promotion of open science and open data sharing (e.g., open wheat blast www.wheatblast.net) which they think very critical for rapidly addressing the emerging plant diseases. |
| Impact | #OpenWheatBlast http://openwheatblast.net https://twitter.com/search?q=%23OpenWheatBlast&src=typd Win, J., Chanclud, E., Reyes-Avila, C.S., Langner, T., Islam, T., and Kamoun, S. 2019. Nanopore sequencing of genomic DNA from Magnaporthe oryzae isolates from different hosts. Zenodo, http://doi.org/10.5281/zenodo.2564950. Valent, B., Farman, M., Tosa, Y., Begerow, D., Fournier, E., Gladieux, P., Islam, M.T., Kamoun, S., Kemler, M., Kohn, L.M.8., Lebrun, M.H., Stajich, J.E., Talbot, N.J., Terauchi, R., Tharreau, D., Zhang, N. 2019. Pyricularia graminis-tritici is not the correct species name for the wheat blast fungus: response to Ceresini et al. (MPP 20:2). Molecular Plant Pathology, 20:173-179. Gupta, D.R., Reyes Avila, C., Win, J., Soanes, D.M., Ryder, L.S., Croll, D., Bhattacharjee, P., Hossain, S., Mahmud, N.U., Mehebub, S., Surovy, M.Z., Rahman, M., Talbot, N.J., Kamoun, S., and Islam, T. 2018. Cautionary notes on use of the MoT3 diagnostic assay for Magnaporthe oryzae Wheat and rice blast isolates. Phytopathology, in press. Islam, T., Croll, D., Gladieux, P., Soanes, D., Persoons, A., Bhattacharjee, P., Hossain, S., Gupta, D., Rahman, Md.M., Mahboob, M.G., Cook, N., Salam, M., Surovy, M.Z., Bueno Sancho, V., Maciel, J.N., Nani, A., Castroagudin, V., de Assis Reges, J.T., Ceresini, P., Ravel, S., Kellner, R., Fournier, E., Tharreau, D., Lebrun, M.-H., McDonald, B., Stitt, T., Swan, D., Talbot, N., Saunders, D., Win, J., and Kamoun, S. 2016. Emergence of wheat blast in Bangladesh was caused by a South American lineage of Magnaporthe oryzae. BMC Biology, 14:84. |
| Start Year | 2016 |
| Description | Evolutionary mechanisms that equip wild potato with disease resistance against the notorious late blight pathogen (Phytophthora infestans) |
| Organisation | Wageningen University & Research |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | Recognising the disease To defend itself the first thing the plant has to do is detect the pathogen. "The plant has receptors for this, a kind of antennas. These bind tiny pieces of Phytophthora protein, which is the signal that something is wrong. This is when the defense responses kick in. So it is very important that the plant can actually detect the disease and has the right receptors in place to activate its defences", says Vleeshouwers. These receptors are located either inside or on the surface of the cell. Receptors inside the cell are encoded by specific R genes (R stands for resistance), and potato breeders take advantage of these. They develop resistant varieties by selecting for these R genes. However, the problem is that the pathogen manages to break through that resistance, time and again. "Much less is known about the receptors on the outside, on the cell surface, the Pattern Recognition Receptors (PRRs). These receptors drive more general immune responses," Vleeshouwers says. Plant breeders are currently focusing their attention on R genes, but there is still a gap to be filled in the fundamental understanding of PRRs before the potential applications and benefits of less specific defensive responses can be explored in breeding robust disease resistance. To this end, Wageningen University & Research is cooperating with the University of Tübingen (Germany) and The Sainsbury Laboratory in Norwich (UK) to study the evolution and diversification of PRRs in potato. |
| Collaborator Contribution | PERU Vleeshouwers explains, "We have been studying a specific type of PRR receptor called PERU. It binds a special piece of Phytophthora protein, Pep-13, which triggers the potato plant to recognise the disease. It was generally assumed that PRR receptors hardly change over time (a well-known example is the very stable receptor that recognises bacteria flagella). But we found that PERU actually exhibits dynamic evolution, and changes much faster than the more well-known PRR receptors. This is a totally new insight." According to co-research leader Thorsten Nürnberger of the Centre for Plant Molecular Biology (ZMBP) at the University of Tübingen, the research results show that the evolution of immune receptors on the cell surface of plants is much more complex than we previously thought. |
| Impact | Sustainable cultivation This insight into this type of receptors (with more to follow) paves the way for the sustainable potato of the future. This sustainable crop could have R genes encoding for specific receptors within the cells, plus enhanced general defensive responses using PRRs on the cell surface. "Before today, breeders focused on R genes. However, the resistance they offer is constantly being thwarted. By studying how wild potato species survive in an environment where they are constantly assailed by diseases, we can discover what mechanisms they use, and then introduce these mechanisms in our own potato varieties," Vleeshouwers concludes. |
| Start Year | 2022 |
| Description | Wheat Disease Early Warning Advisory System (Wheat DEWAS) |
| Organisation | International Centre for Maize and Wheat Improvement (CIMMYT) |
| Country | Mexico |
| Sector | Charity/Non Profit |
| PI Contribution | CIMMYT has launched the Wheat Disease Early Warning Advisory System (Wheat DEWAS), funded through a $7.3 million grant from the Bill & Melinda Gates Foundation and the United Kingdom's Foreign, Commonwealth & Development Office, to enhance crop resilience to wheat diseases. Wheat DEWAS is designed to help safeguard wheat productivity and advance sustainable agricultural practices in collaboration with international partners, including researchers at the John Innes Centre, The Sainsbury Laboratory and GetGenome. |
| Collaborator Contribution | Led by David Hodson from CIMMYT and Maricelis Acevedo from Cornell University, this ambitious project brings together a global team of experts. Professor Sophien Kamoun is particularly delighted to expand collaboration with CIMMYT and African scientists, developing and expanding the cutting-edge platforms for genomic surveillance of wheat pathogen. Open science and international collaborations were at the core of the successful tracing and identification of wheat blast clones after the devastating wheat disease spread to two other continents. By creating the website Open Wheat Blast, the rapid sharing of data was facilitated between researchers, which proved crucial for tracking wheat blast pathogens and ensured that all contributions were appropriately credited. This resulting publication was recently highlighted as an exemplary way of working with the Global South in an article calling for more collaborative authorship practices. GetGenome, a charitable initiative that aims to provide equitable access to genomic technologies, was inspired by these principles and is designed to enable open science and data sharing with contributions properly credited from the start. |
| Impact | The combination of rapid identification of emerging variants together with pathotyping to assess the variants' potential to impact wheat production will inform the generation of a list of Variants of Concern. This valuable data will be shared with project partners and contribute to the deployment of effective disease management strategies. |
| Start Year | 2023 |
| Company Name | Resurrect Bio |
| Description | Resurrect Bio develops gene editing technology designed to resurrect R-genes in crops such as soy, aiming to provide a more sustainable alternative to chemical agricultural controls. |
| Year Established | 2021 |
| Impact | Delivering disease resistance traits. Integrating AI into plant disease resistance breeding. |
| Website | http://resurrect.bio |
| Description | SchoBozKa Annual Retreat |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | The event is an annual retreat of the following labs to enable interactions between the team members and explore research avenues. This also includes a career development activity. The groups involved are Sebastian Schornack @dromius | Tolga Bozkurt @Tolga_Bzkrt | Lida Derevnina @lderevnina | Phil Carella @Phil_Carella | Jiorgos Kourelis @JiorgosKourelis |
| Year(s) Of Engagement Activity | 2023,2024,2025 |
| URL | https://kamounlab.tumblr.com/post/776102920337915904/its-that-time-of-year-schobozka-running-strong |
| Description | TSL Symposium - Plant resistance to pathogens in the face of climate change |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | The symposium held on November 4th, 2024, in Norwich. This event marks the launch of the strategic partnership between The Sainsbury Laboratory and the Khalifa Center for Genetic Engineering and Biotechnology. Our collaboration aims to advance climate-resilient plant immunity research by uniting our expertise in plant-pathogen interactions specific to desert and dryland plants. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://kamounlab.medium.com/opening-remarks-tsl-symposium-plant-resistance-to-pathogens-in-the-face... |