Structural Biology of pathogen:host interactions
Lead Research Organisation:
John Innes Centre
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
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.
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.
Planned Impact
unavailable
Publications
Sato K
(2009)
Metal-binding loop length and not sequence dictates structure.
in Proceedings of the National Academy of Sciences of the United States of America
Race P
(2009)
Crystal Structure of Streptococcus pyogenes Sortase A
in Journal of Biological Chemistry
Smith WD
(2010)
Roles of minor pilin subunits Spy0125 and Spy0130 in the serotype M1 Streptococcus pyogenes strain SF370.
in Journal of bacteriology
Badarau A
(2010)
Visualizing the metal-binding versatility of copper trafficking sites .
in Biochemistry
Solovyova AS
(2010)
Solution structure of the major (Spy0128) and minor (Spy0125 and Spy0130) pili subunits from Streptococcus pyogenes.
in European biophysics journal : EBJ
Boutemy L
(2011)
Structures of Phytophthora RXLR Effector Proteins
in Journal of Biological Chemistry
Li C
(2011)
Metal-binding loop length is a determinant of the pKa of a histidine ligand at a type 1 copper site.
in Inorganic chemistry
Wirthmueller L
(2011)
Crystallization and preliminary X-ray analysis of the RXLR-type effector RXLR3 from the oomycete pathogen Hyaloperonospora arabidopsidis.
in Acta crystallographica. Section F, Structural biology and crystallization communications
Win J
(2012)
Sequence divergent RXLR effectors share a structural fold conserved across plant pathogenic oomycete species.
in PLoS pathogens
Giacomelli L
(2012)
Identification and characterization of the defensin-like gene family of grapevine.
in Molecular plant-microbe interactions : MPMI
| 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 | 07/2015 |
| End | 07/2018 |
| Description | ERC Advanced Investigator |
| Amount | € 2,500,000 (EUR) |
| Funding ID | BLASTOFF 743165 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 08/2017 |
| 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 |
