Trehalose signalling: understanding and exploiting an emerging small molecule carbohydrate paradigm

Lead Research Organisation: Rothamsted Research
Department Name: Plant Biology & Crop Science

Abstract

Sucrose and trehalose are the most widespread non-reducing disaccharides in nature. Sucrose functions as an energy reserve, building block and protective molecule in plants, and trehalose has these functions in fungi, bacteria and insects. Until recently, with very few exceptions, this division of sucrose and trehalose between the kingdoms was thought to be clear cut. However, the trehalose pathway and trehalose 6-phosphate, in particular, have been shown to play an indispensbale signalling role in plants influencing processes like photosynthesis, sugar metabolism, disease and stress resistance. The proposal will determine signalling partners of trehalose 6-phosphate and closely related non-reducing disaccharides in plants to enable chemical intervention of these important plant processes in Arabidopsis with a longer term view to crop improvement.

Technical Summary

This proposal is driven by 1) the pressing biological question of the site of interaction of the disaccharide trehalose 6-phosphate (T6P) following its discovery as part of an indispensable signalling mechanism with significant effects on photosynthsis, sugar metabolism, disease and stress resistance in Arabidopsis; 2) the recent availability of methods in the field of glycomics, carbohydrate and protein chemistry that enable probing for the site of interaction of T6P and related compounds and the chemical intervention of its physiological function in planta. The chemical intervention approach is focused on synthesis of non-reducing glycan libraries based on the trehalose and sucrose cores. From these, small molecule glycan arrays will be made to enable the isolation of protein and nucleic acid partners. State-of-the-art protein separation and gene cloning will be used to characterise the binding partners. Construction of in planta active non-reducing mimetics and probes will enable chemical intervention in vivo.

Publications

10 25 50
 
Description The trehalose pathway is an important target for the modification of growth, development and yield. Genetic modification of the pathway in maize is producing large yield increases in the field. In collaboration with Oxford University and ISIS Innovations we have developed and patented novel chemical approaches to modifying trehalose 6-phosphate (T6P) levels in plant cells. This technology involves the application of UV-labile chemicals which enter plant cells and release T6P upon exposure to sunlight, demonstrating the first uncaging of sugar molecules in a plant. We have shown beneficial effects of this technology through enhancement of starch synthesis in Arabidopsis. The technology has attracted interest from industrial sources including Syngenta. Chemical approaches offer an attractive supplementary approach to GM, particularly in Europe, but also in other grain-growing regions which may be reluctant to accept GM technology for crops such as wheat. Chemical approaches offer the additional attraction that they can be applied dependent on the weather in a particular season which in Europe can alternate between drought and flooding in consecutive years.
Exploitation Route We have increased wheat grain size and ability of plants to recover from drought. There does seem substantial potential of this work to improve crop yields, at least for wheat and to increase fundamental understanding of the regulation of sucrose allocation and use in plants and crops as a new regulatory hub for crop yield improvement.
Sectors Agriculture, Food and Drink,Chemicals,Environment,Manufacturing, including Industrial Biotechology

URL https://www.nature.com/articles/nature20591
 
Description This work was published in Nature (Chemical intervention in plant sugar signalling increases yield and resilience. Griffiths et al. 2016, doi: 10.1038/nature20591) https://phys.org/news/2016-12-wheat-crop-yield-chemical-technology.html and has yielded 3 patents and a spin out company to be incorporated in March 2018. Field trials of the T6P precursors are expected to take place in 2018/ 2019. The work has great prospects for improving crop yield and food security.
First Year Of Impact 2016
Sector Agriculture, Food and Drink,Chemicals
Impact Types Economic

 
Description Direct funding from industrial partner, ICL
Amount £73,982 (GBP)
Organisation Imperial College London 
Sector Academic/University
Country United Kingdom
Start 06/2014 
End 11/2014
 
Description Technology Innovation Programme
Amount £49,000 (GBP)
Organisation Rothamsted Research 
Sector Academic/University
Country United Kingdom
Start 06/2014 
End 02/2015
 
Description Oxford University 
Organisation University of Oxford
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution We have tested caged T6P compounds made by Oxford University
Collaborator Contribution Oxford University has synthesised novel caged T6P compounds
Impact 1 published patent; 1 patent application increased wheat grain size and recovery from drought
Start Year 2006
 
Description iCL 
Organisation ICL Innovation
Country Israel 
Sector Private 
PI Contribution analysis of effects of caged T6P on wheat yield
Collaborator Contribution provision of funding
Impact a publication has been submitted for publication
Start Year 2014
 
Description iCL 
Organisation ICL Innovation
Country Israel 
Sector Private 
PI Contribution analysis of effects of caged T6P on wheat yield
Collaborator Contribution provision of funding
Impact a publication has been submitted for publication
Start Year 2014
 
Title MODIFICATION OF TREHALOSE-6-PHOSPHATE LEVELS IN PLANTS 
Description Compounds which are trehalose-6-phosphate or trehalose-6-phosphonate precursors of formula (I) or agriculturally acceptable salts thereof are provided: (I) The compounds are useful in increasing starch production in plants. 
IP Reference WO2012146914 
Protection Patent granted
Year Protection Granted 2012
Licensed Yes
Impact The compounds impact recovery of wheat plants from drought. Additionally, they increase grain size of wheat.
 
Title TREATING WATER STRESS IN PLANTS 
Description The present invention relates to methods and uses of photo-labile compounds which are trehalose-6-phosphate or trehalose-6-phosphonate or agriculturally acceptable salts thereof in the treatment of water stress in plants. The invention also concerns methods and the use of the compounds for resurrection of water stressed plants, and for improvement of yield of crop plants under water stressed conditions compared with untreated plants. 
IP Reference WO2017006095 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact Nature publication doi:10.1038/nature20591
 
Company Name SUGAROX LIMITED 
Description Work funded by BBSRC has enabled us to discover a mechanistic basis for sugar signalling in plants and crops. Trehalose 6-phosphate (T6P) is a sugar signal that promotes growth and development and metabolic reprogramming through a protein kinase, SnRK1. Chemical modification of T6P to enable uptake into plants has shown through application as a spray that T6P can increase crop yields in field conditions. SugaROx was formed to take forward IP from patents regarding yield enhancement, recovery from drought, stimulation of flowering and suppression sprouting. So far focus has been on wheat, but it is likely that T6P spray will have wide application for many crops. 
Year Established 2018 
Impact The company has only just been formed and as yet there are no impacts
 
Description Conference talk, Sainsbury lab 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Induced Plant Development, Sainsbury Lab
Year(s) Of Engagement Activity 2016
 
Description Gordon Conference Switzerland, salt and water stress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact conference talk
Year(s) Of Engagement Activity 2016
 
Description Plant Genomics Conference, Malaysia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact conference seminar
Year(s) Of Engagement Activity 2016
 
Description SCI New Frontiers in Crop Research 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact conference talk
Year(s) Of Engagement Activity 2016
 
Description SEB conference, Brighton 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact conference talk
Year(s) Of Engagement Activity 2016
 
Description media coverage 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact media coverage following Nature publication
Year(s) Of Engagement Activity 2016
URL http://www.dailymail.co.uk/sciencetech/article-4035332/Crop-spray-makes-wheat-20-larger-s-GM-free-Mo...
 
Description media coverage 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact media coverage following Nature publication
Year(s) Of Engagement Activity 2016
URL http://www.telegraph.co.uk/science/2016/12/14/monster-wheat-grown-oxford-could-revolutionise-farming...
 
Description media coverage 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact media coverage following Nature publicaiton
Year(s) Of Engagement Activity 2016
URL http://www.reuters.com/video/2017/01/23/wheat-grain-size-boosted-by-synthetic-ch?videoId=370975942&v...
 
Description media coverage 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact media coverage following Nature publication
Year(s) Of Engagement Activity 2016
URL https://www.ft.com/content/c42893aa-c22a-11e6-9bca-2b93a6856354
 
Description media coverage 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact media coverage following Nature publication
Year(s) Of Engagement Activity 2016
URL http://www.theglobeandmail.com/report-on-business/video/wheat-grain-size-boosted-by-synthetic-chemic...
 
Description media coverage 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact media coverage following Nature publication
Year(s) Of Engagement Activity 2016
URL https://www.yahoo.com/news/wheat-grain-size-boosted-synthetic-123548758.html
 
Description media coverage 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact media coverage following Nature publication
Year(s) Of Engagement Activity 2016
URL http://www.msn.com/en-us/video/w/wheat-grain-size-boosted-by-synthetic-chemical/vp-AAm8JwO
 
Description media coverage 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact media coverage following Nature publication
Year(s) Of Engagement Activity 2016
URL https://phys.org/news/2016-12-wheat-crop-yield-chemical-technology.html