Tuning the sensor of an immune receptor

Lead Research Organisation: University of East Anglia
Department Name: Sainsbury Laboratory

Abstract

Pathogens use a suite of effector proteins that target host proteins to subdue immune systems and enable infection of the host. Occasionally, a pathogen strain evolves to infect a new host - a process known as a "host jump". Host jumps exert a strong selection pressure on the effectors to adapt to their new host environment, ultimately leading to effector and pathogen specialization. This project investigates pathogen adaptation and effector specialization after a host jump in the rice blast fungus, a complex pathogen of grasses. The rice blast fungus is critical for global food security as the main destroyer of the rice crop. It secretes a multitude of effectors. Avr-Pik is one such effector that targets rice proteins containing heavy metal associated (HMA) domains to enhance virulence. However, rice uses HMAs as sensors integrated in an immune receptor that detects Avr-Pik to mount defence. Recently, the crystal structure of a complex between Avr-Pik and the HMA from the immune receptor Pikp has been determined in our Laboratories. We showed that the affinity between Avr-Pik and HMA determined the sensitivity of the immune receptor. This offers an unprecedented opportunity to study the effect of natural variations on affinity between Avr-Piks and HMAs at the biochemical level. This project aims to exploit natural variation in effector and host proteins to fine-tune the sensor in Pikp to recognize a broader range of blast fungi.

Publications

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Bialas A (2018) Lessons in Effector and NLR Biology of Plant-Microbe Systems. in Molecular plant-microbe interactions : MPMI

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Zess EK (2019) Old fungus, new trick. in Nature microbiology

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 01/10/2015 30/09/2023
1771322 Studentship BB/M011216/1 01/10/2016 30/09/2020 Aleksandra Bialas
 
Description The Oryza genus has evolved the Pik-1 and Pik-2 proteins-a pair of NLR immune receptors that confer disease resistance to the rice blast fungus, Magnaporthe oryzae. Although the Pik-2 protein has a typical NLR domain architecture, Pik-1 carries an unconventional Heavy Metal-Associated (HMA) domain that directly binds the M. oryzae AVR-Pik effector. We aim to understand the evolutionary history of the Pik-1 receptor and test hypotheses about the adaptive evolution of its integrated HMA domain. Phylogenetic analyses of Pik orthologues indicated that the HMA domain integrated into Pik-1 nearly 50 million years ago. Ancestral HMA sequence reconstruction coupled with functional studies revealed that different allelic variants of Pik-1-Pikp-1 and Pikm-1-convergently evolved to recognise AVR-PikD. Using biophysical approaches, we functionally characterised two regions in the Pik-1 HMA that independently evolved towards high-affinity AVR-PikD binding from the weaker ancestral state. In both cases the HMA domain only recently acquired the capacity to bind the AVR-PikD effector with high affinity, indicating that for most of its evolutionary history the HMA was not subject to selective pressure imposed by this blast effector. In addition, although Pikp-1 and Pikm-1 receptors evolved to produce a similar phenotypic outcome, they underwent different evolutionary trajectories to do so. These findings indicate that the evolution of NLR receptors is even more dynamic than previously thought.
Exploitation Route We'd like to further characterise the regions in Pikp-1 and Pikm-1 receptors that evolved high binding affinity to AVR-PikD effector. This knowledge can be utilized in NLR receptor engineering.
Sectors Agriculture, Food and Drink

 
Description BLASTOFF 
Organisation John Innes Centre
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution I been involved in regular meetings and conversation widely related to the Pik-mediated immune resistance in rice, and provided Mark Banfield and his group with some useful constructs.
Collaborator Contribution Prof. Mark Banfield provided an intellectual support, mostly in the field of biophysics, as my secondary supervisor. He and his group has been involved in regular meetings and conversation widely related to the Pik-mediated immune resistance in rice, and provided me with some useful constructs.
Impact Bialas A, Zess EK, De la Concepcion JC, Franceschetti M, Pennington HG, Yoshida K, Upson JL, Chanclud E, Wu CH, Langner T, Maqbool A, Varden FA, Derevnina L, Belhaj K, Fujisaki K, Saitoh H, Terauchi R, Banfield MJ, Kamoun S. Lessons in Effector and NLR Biology of Plant-Microbe Systems. Mol Plant Microbe Interact. 2018 Jan;31(1):34-45. doi: 10.1094/MPMI-08-17-0196-FI.
Start Year 2016
 
Description BLASTOFF Japan 
Organisation Iwate Biotechnology Research Centre
Country Japan 
Sector Public 
PI Contribution We have an ongoing collaboration with Prof Ryohei Terauchi and his lab how we exchange research information on the regular basis.
Collaborator Contribution We have an ongoing collaboration with Prof Ryohei Terauchi and his lab how we exchange research information on the regular basis.
Impact Bialas A, Zess EK, De la Concepcion JC, Franceschetti M, Pennington HG, Yoshida K, Upson JL, Chanclud E, Wu CH, Langner T, Maqbool A, Varden FA, Derevnina L, Belhaj K, Fujisaki K, Saitoh H, Terauchi R, Banfield MJ, Kamoun S. Lessons in Effector and NLR Biology of Plant-Microbe Systems. Mol Plant Microbe Interact. 2018 Jan;31(1):34-45. doi: 10.1094/MPMI-08-17-0196-FI.
Start Year 2016
 
Description CSHL conference attendance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Attendance and a talk at the Plant Genomes & Biotechnology: From Genes to Networks Meeting, Cold S Cold Spring Harbor Laboratory, New York
Year(s) Of Engagement Activity 2017
 
Description Norwich Science Festival science communication 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Noriwich Science Festival open to general public where they could learn about plant-microbe interaction and science in general.
Year(s) Of Engagement Activity 2017,2018
 
Description Organising Undergrad JIC Summer School practical Undergrad JIC Summer School 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact 20 undergrads were thought about plant-microbe interaction in a workshop setup
Year(s) Of Engagement Activity 2016,2017
 
Description attendance "4th Annual Conference of the COST Action" meeting 4th Annual Conference of the COST Action,Slovenia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact I presented a poster about my PhD research,
Year(s) Of Engagement Activity 2017
 
Description attendance and presentation at the Evolutionary Biology Meeting, France, 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact I have given a talk and presented a poster about my PhD research to the scientists from the filed of Evolutionary Biology.
Year(s) Of Engagement Activity 2018