Pathogen effector proteins that target the host plant S-nitrosylation machinery

Supervisors: Gary Loake, David Clarke

Project description:

A conspicuous feature of the immune response is the production of nitric oxide (NO) which has been proposed to orchestrate a plethora of defence responses. NO bioactivity is predominately mediated by S-nitrosylation, the addition of an NO moiety to a cysteine thiol to form an S-nitrosothiol (SNO). S-glutathione reductase (GSNOR) and thioredoxin h5 (TRXh5) indirectly or directly respectively, control the global cellular levels of S-nitrosylation. Loss-of-function mutations in these enzymes results in dysregulation of S-nitrosylation strikingly compromising plant disease resistance across species. These key regulatory proteins might therefore present excellent targets for pathogen virulence factors, as their disablement would convey enhanced disease susceptibility. 

Barley (Hordeum vulgare), is the second most widely grown crop in the UK. The fungal pathogen, Blumeria graminis f. sp. hordei (Bgh), is responsible for major barley yield losses. Bgh encodes a suite of effector proteins that are delivered to the inside of barley cells to aid pathogenesis. We have identified four barley effector proteins that strongly interact with either GSNOR or TRXh5, disabling their cellular function.

This project will explore the potential contribution of these four effector proteins to Bgh pathogenesis of barley and the possible consequences of GSNOR or TRXh5 inhibition to the barley immune response. Further, the mechanism of effector inhibition of GSNOR and TRXh5 will be characterised by employing cutting-edge chemical technologies. We anticipate insights gained from this research will provide novel insights towards barley crops exhibiting enhanced and durable resistance against Bgh, exploiting pioneering gene editing technologies and other emerging genomic-based tools. 

Collectively, this project will provide the PhD student with interdisciplinary training in plant genetics, synthetic biology, molecular biology, plant pathology, genomics and cutting-edge chemical technologies.

References:

Yun, B-W., Feechan, A., Yin, M., Saidi, N. B.B., Yu, M., Le Bihan, T. Kang, J.-G., Kwon, E., Spoel, S., Pallas, J.A. and Loake, G.J. (2011). S-nitrosylation of NADPH oxidase regulates cell death in plant immunity. Nature 478, 264-268.

Feechan, A., Kwon, E.-J., Yun, B.-W., Wang, Y., Pallas, J.A. and Loake, G.J. (2005). A Central Role for S-Nitrosothiols in Plant Disease Resistance. Proc. Natl. Acad. Sci. USA 102, 8054-8059.

Kneeshaw, S., Gelineau, S., Tada, Y., Loake G.J., and Spoel, S.H. (2014). Selective Protein Denitrosylase Activity of Thioredoxin-h5 Modulates Plant Immunity. Mol. Cell 56, 153–162.

 

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