Structural Biology of pathogen:host interactions

Lead Research Organisation: John Innes Centre
Department Name: Contracts Office

Abstract

The primary aim of the research group is to investigate the mechanisms of pathogen:host interaction during infection/colonization at the molecular level. We use a range of structural biology techniques to understand the function of specific proteins and how they interact with their environment. Some current priorities include establishing structure/function relationships in ‘effector’ proteins from pathogens important for human/mammalian health and agriculture (e.g. Enteropathogenic E. coli (EPEC), Phytophora infestans (the Irish potato famine pathogen)), and mechanisms of pili biogenesis in Group A Streptococcus. Our primary experimental tool is structure determination by X-ray crystallography, but we also complement this with solution-based methods (circular dichroism, isothermal titration calorimetry, surface plasmon resonance, analytical ultracentrifugation, small angle X-ray scattering, spectroscopy) as appropriate. Structural data is frequently used to establish hypotheses which can then be tested, for instance, by site-directed mutagenesis and further study. We collaborate extensively with groups in Norwich, the UK and worldwide to ensure the in vivo relevance of our in vitro data.

We also have an interest in developing/employing new technologies to advance throughput in protein production and structure determination to both streamline our current research projects and enhance the feasibility of establishing new projects in the Laboratory.

Publications

10 25 50
 
Description This grant has funded my core activities at the John Innes Centre from 2008 - 2017 (before the start of the current Institute Strategic Program awards). As such, the research funded spans the range of activities undertaken in my Lab and has, in part, underpinned all studies. It has enabled us to investigate how microbial pathogens use proteins (termed "effectors") to manipulate plant cell processes for the benefit of the invading organism. Specifically, we have determined the three-dimensional structures of such proteins, and combined these with other biochemistry and in planta assays to understand how they function and contribute to promoting disease. Understanding how microbial pathogens use molecules such as proteins to cause disease on plants is fundamentally interesting, but also gives us tools with which to investigate host cell function. For example, to determine how particular communication pathways in cells interact with each other for a similar outcome.

Effectors are also an Achilles' heel for pathogens, as plants have evolved their own proteins to detect the presence of these molecules. These immune receptors can directly bind to pathogen effectors, and we have studied such interactions in my Lab. Specifically we have used an immune receptor from rice, and effectors from the most devastating fungal disease of rice, known as "Blast". By understanding the fine molecular details of how such receptors bind to specific effector proteins, we aim to engineer improved activities to promote plant health in some of the world's most important crops.
Exploitation Route This research could inform researchers/scientists/breeders interested in plant disease and specifically engineering novel mechanisms for crop disease resistance.
Sectors Agriculture, Food and Drink

 
Description An effector-detector domain in a rice immune receptor: towards structure-guided design of new disease resistance proteins.
Amount £420,650 (GBP)
Funding ID BB/M02198X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2015 
End 07/2018
 
Description ERC Advanced Investigator
Amount € 2,500,000 (EUR)
Funding ID BLASTOFF 743165 
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 09/2017 
End 08/2022
 
Description Molecular mechanisms of virulence and avirulence in the Avr3a family of Phytophthora.
Amount £405,119 (GBP)
Funding ID BB/I01957X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2011 
End 11/2014
 
Description Collaboration with Lab of Ryohei Terauchi at IBRC in Iwate and Kyoto University, Japan 
Organisation Iwate Biotechnology Research Centre
Country Japan 
Sector Public 
PI Contribution Leading collaborative research project on Structure/function studies of rice blast disease and host resistance.
Collaborator Contribution Collaborative work on research project.
Impact Research publications and BBSRC grant funded (M02198X).
Start Year 2011
 
Description Plant Doctors day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Orgainsed/ran a "Plant Doctors" Day for ~55 Year 6 students at a local school with the Outreach team from the British Society for Plant Pathology
Year(s) Of Engagement Activity 2014
URL http://www.bspp.org.uk/outreach/article.php?id=126
 
Description SAW (Science, Art and Writing) day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact SAW (Science, Art and Writing) day at Chapel Break Infant School in Oct 2009
Year(s) Of Engagement Activity 2009
 
Description Seminar at University of Queensland, Australia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research or patient groups
Results and Impact Seminar delivered during visit to the University of Queensland, Australia describing the work conducted during this grant.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description Teacher-Science-Network 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Teacher Scientist Network (TSN), linked with local schools in Hethersett (co-ran Science afternoon for Year 6 pupils, June 2012)
Year(s) Of Engagement Activity 2012