Understanding a mutant that disregulates trehalose 6-phosphate action in plants

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Understanding how plants sense and respond to sucrose is a fundamental question in biology. It has become apparent that trehalose 6-phosphate (T6P), is a central part of the sensing and signalling system for sucrose - affecting all processes involved in whole plant carbon management and metabolism and the integration of sucrose supply with growth and development. Significantly, modification of T6P levels in crops has resulted in significant improvements in yield and resilience. We have discovered that T6P inhibits the feast/famine protein kinase, SnRK1 and that this can be chemically probed and manipulated through a strategy of 'synthetic signalling precursors' [Griffiths et al. (2016) Nature]; yet even so, the fundamental molecular basis of the T6P signalling mechanism and how plants regulate the accumulation of T6P remains largely unknown.

We have now assembled a wide-ranging multilateral consortium built on a framework of several successful, established bilateral partnerships within and between Oxford and Rothamsted. This creates a unique, critical mass grouping that will use a spectrum of methods in chemical biology, structural biology, metabolomics, proteomics, molecular plant genetics and plant physiology to test new hypotheses. Specifically, recent unpublished insights suggest: 1) TPS7 is a negative regulator of T6P accumulation; 2) TPS7 interacts with TPS1 and/ or SnRK1 to regulate T6P accumulation; 3) Other class II TPSs (TPS5-11) perform similar functions to TPS7. 4) The regulation of T6P accumulation by class II TPSs is of key importance in understanding sucrose and T6P signalling and hence the regulation of carbon allocation in plants with further future potential application in crop improvement. These create a new central regulatory paradigm for the regulation of T6P accumulation and hence all the downstream sucrose and carbon management processes that depend on T6P.

These hypotheses will be addressed in four work packages (see Objectives).

Sugars are a pivotal component of all biological processes; thus, the impacts of knowing how plants regulate the accumulation of the major sucrose signal in plants, trehalose 6-phosphate (T6P) will be major and wide ranging. T6P impacts all key functions in plant growth and development: growth rates, biomass accumulation, partitioning into primary/secondary metabolites and end products, integration of environmental signals, symbiotic and pathogenic interactions, photosynthesis and processes such as architectural development, senescence and flowering. Researchers in these areas will benefit from our fundamental advances.
Sugar biology underpins global ecosystems and agriculture. The modification of sucrose use and allocation in crops through the T6P system is emerging as one of the most promising targets in crop improvement for yield, abiotic stress resilience and other traits through whole plant sugar and carbon management in wheat, rice and maize. Hence, agricultural scientists and plant breeders will benefit from molecular insights and trait assessments.
The central role of plants in harvesting solar energy makes development of long-term plant sources of food, fuel and chemicals a vital goal. Plant sugars have the potential to serve as pre-cursors in all of these domains, thus ensuring 'sugar security', i.e. polysaccharide supplies, from plants must be prioritised. Knowledge of plant fixation of carbon from the atmosphere, a process tied to sugar sensing and allocation, will inform novel climate change mitigation. Therefore, results from this programme will be of interest to synthetic biologists, chemists and researchers focused on alternative energy production.
Knowledge of how plants regulate sugar homeostasis parallels other systems: blood sugar control is central to many human health conditions of growing concern in the UK and globally (linked to another glucose-polymer glycogen). Pan-kingdom energy sensors AMPK/SNF1 affect metabolic syndrome, cancer, ageing and longevity. Fundamental knowledge of sugar-sensing, signalling and homeostasis could stimulate and synergise with other systems in medicine and healthy ageing.
International collaboration and dissemination will be substantial through existing and developing networks. Davis (PI) is a member of 4 European collaborative networks using chemical tools in organismal systems and on-going collaborative links with >15 institutions globally, including e.g. the NIH. The Co-Is have >30 national and international collaborations exploring e.g. use of RNA-seq, proteomics, metabolomics and structural methods. Research staff will benefit from specialist training in state-of-the-art tools, resources, methodologies and equipment at all sites through rotations.
Spin-out company, SugarROx, formed by Rothamsted and Oxford for crop translation of previous BBSRC-funded outputs, highlights long-term economic and social legacy to be strengthened here by complementary fundamental science. Three patents are granted/pending. In tech-transfer with Oxford University Innovations (OUI) we liaise with >200 potential partners in varying sectors incl. on-going partnerships with multi-nationals (in various fields) enabling rapid development of new opportunities. OUI are also proactive in the management of relationships with those handling IP portfolios and potential future partners. Although it is not the primary driver, programme outputs will have long-term impacts on UK agri-business and food supply chains.
The ability to 'rescue from drought' enabled by this technology will free communities in developing (& increasingly in developed) countries from vicious cycles of dependency (driven by climate change / dwindling water). It therefore, provides resilience in food systems and action on both environmental 'shock' and long-term environmental change in a manner that promotes humanitarian action by returning independence to those affected.