Award details

SUMOcode: deciphering how SUMOylation enables plants to adapt to their environment

Reference	BB/V003534/1
Principal Investigator / Supervisor	Professor Ari Sadanandom
Co-Investigators / Co-Supervisors	Dr Jonathan Atkinson, Dr Leah Band, Professor Malcolm Bennett, Dr Rahul Bhosale, Dr Anthony Bishopp, Professor Alistair Darby, Dr Miguel De Lucas, Professor Andrew Jones, Professor Kathryn Lilley, Dr Diarmuid Seosamh O'Maoileidigh, Professor David Salt, Dr Darren Wells
Institution	Durham University
Department	Biosciences
Funding type	Research
Value (£)	3,647,367
Status	Current
Type	Research Grant
Start date	01/03/2021
End date	28/02/2026
Duration	60 months

Abstract

Post-translational modification (PTM) events generate proteoforms that orchestrate cell signalling in almost every biological process. The SUMOcode project aims to understand a critically important but understudied PTM in plants, SUMO (Small Ubiquitin-like Modifier). The rules governing specificity and function remain rudimentary for most PTMs, but the plant SUMO system provides a unique possibility to unravel the rules governing SUMOylation, as its core machinery comprises only 33 genes in Arabidopsis, compared with many hundreds for other PTMs. Our central hypothesis is that SUMO specificity is conferred through how cells are primed to respond to different stress signals, the tissue and cellular spatial distribution of SUMO machinery and substrates and control of SUMOylation modification via activation, repression and competition for PTM sites. Given the small numbers of genes involved in SUMOylation, we are in an excellent position to test our hypothesis employing state of the art multi-omics technologies to create the first SUMO Cell Atlas of any organism. First, we will map expression and modification of SUMO components in Arabidopsis root cells and their responses to biotic and abiotic stresses and REDOX regulation. Secondly, we will identify key SUMOylated regulatory nodes acting as master response coordinators. Exploiting phenomic and single cell transcriptomic approaches, we will determine how the SUMO code remodels transcription in different cell types to trigger adaptive responses. Finally, we will translate the SUMO code across the plant kingdom and reveal natural variation in crop genomes through an online portal and worked exemplars to demonstrate the value of the SUMO code, its machinery and regulatory targets. Our ultimate goal is to 'enable' researchers and breeders to decipher the SUMO code in plants, enabling them to edit and rewrite the code, to develop crops that are future proofed against ongoing climate instability and change.

Summary

At a basic level the rules that govern life is defined by an organism's genetic code (like the text of a book) and the signals it receives from the environment (like the interpretation of the reader of the text). The combination of these two (the genetic code and the signals) makes an organism behave and develop the way it does. At a molecular level there are several critical systems that control the way an organism responds to its environment. These can be (1) long-term responses through the silencing of the genetic code (like removing parts of the text in the book so it can't be interpreted) or (2) more rapid responses through modifications of the system (like annotation to parts of the text of a book which changes the way it is interpreted). Understanding these responses is essential to our understanding of how an organism functions and how an organism changes based on their environment. Here we are focusing on the second type of response, which at a molecular level are initiated by "post-translational modifications (PTMs)" (this a way of changing the function of the existing machinery in a cell). PTMs act at the core of every biological system. Taking signals from outside the cell and "coding" molecular interactions to change the way cells function. This is critical in every biological process. There are several types of PTMs, but one of the most important but whose code is not defined is SUMOylation. Here we aim to take a holistic approach to understanding the SUMO code. In this programme we will develop a SUMO machinery cell atlas (a resource that will characterize each part of the machinery), how, in which cells and when it works, so that a map of the key events that trigger a SUMOylation response to environmental cues can be revealed. We will use the model plant, Arabidopsis, arguably the best non-human, multicellular organism for this scale of interrogation. It has a plethora of tools and resources that will allow us to dissect the SUMO code in detail andacross different cell types, different stages of development and across different response times. This mapping of SUMOylation will reveal the 'hubs' that the SUMO machinery targets to cause a cellular response, revealing how the pathway functions and how it can be manipulated to combat environmental challenges or disease. SUMOylation has already been shown by our group and others that it is important for the way a cell responds to environmental stresses. For example, plants adapt to changes in their environment (heat, water availability, salt, etc) by modifying their growth and development (to enhance their ability to survive and flourish), through PTMs like SUMOylation. Therefore, a key output of this programme will be a set of tools that will translate the SUMO language across the plant kingdom and provide insights into animal and human health and disease. Our ultimate goal is to 'enable' researchers from a range of disciplines, plant breeders, chemical companies and beyond to edit the SUMO code discovered here to improve crop resilience, future proofing them against ongoing climate instability and change, and to catalyse new insights across plants and animals into the rules that govern an organisms behaviour and responses to the environment that surrounds them.

Impact Summary

The SUMOcode project has significant potential for short and longer-term impact: 1. Academic impact and engagement The SUMO Cell Atlas (SCA) integrating dynamic Bioimaging, Interactomics, ROS, SUMOylome and transcriptomics datasets, freely accessible via a web-interface, underpins the project's academic impact. Query and visualisation tools (image maps, networks of interactions e.g. using CytoScape), with link outs to raw data (see Data Management Plan) will enable data re-use by different users (e.g. lab scientists and bioinformatics groups). Users will be able to query if their protein of interest is a SUMO target and likely interaction points with the SUMO system. Omics data will also be mirrored at the BAR website (LOS Prof Provart), enabling wider integration of results on SUMO with other data sets collected for Arabidopsis, thereby guaranteeing reaching a wider user base. The tools and technologies generated will form the basis of two workshops designed to engage with academic and industry stakeholders. 2. Engagement with crop scientists and agri-industry: Social and Economic Impact There is a clear route for exploiting SUMOcode results and datasets to breed new germplasm. For example, understanding natural variation at PTM sites on key Hub proteins that confer a/biotic tolerance will expedite the search for agronomically useful alleles in crop species. Similarly, developments in WP4 will also facilitate translation of results to crops with sequenced genomes (e.g. based on motif conservation for confirmed SUMO sites in Arabidopsis), along with ortholog mapped interaction maps. These resources will enable commercial partners to generate molecular markers to select for desirable traits, leading to new patents, lines and products. In addition, input from the External Advisory Board (EAB) which contains world leading experts in major crops like rice and wheat (e.g. Julia Bailey-Serres, UC, Riverside; Amelia Henry, IRRI; Alison Bentley, NIAB) will be invaluable. 3. Education activities and training. The PDRAs will also benefit from working in a multidisciplinary team, spanning areas such as protein biochemistry, cell biology, phenomics and advanced computational analyses, to build capacity in areas of under-represented, transferrable skills. The project will also develop highly skilled researchers with expertise in cutting edge techniques (e.g. scRNAseq) through movement of PDRAs between partner's and collaborator labs for training (see LOS, Bert de Rybel). PDRAs, PI and co-Is will also offer training for staff and visitors not formally associated with the project through workshops to engage academic and industry stakeholders (in collaboration with organisations and consortia such as GARNet and DFW; see LoS). The development of new fellowship projects to mine data and develop mathematical methods will also add substantial value and impact to the project. 4. Public engagement Public dialogue plays an important role in our institutions' engagement strategy and all activities, supported by the respective Communications teams, will use a wide variety of traditional outlets (e.g. press releases) and new media platforms (e.g. twitter). 5. International Impact There is a global need for faster plant breeding given the impact of climate change. We have identified several areas for collaboration with ODA-recipient countries, facilitated by the EAB and strategic initiatives with overseas partners, particularly those developing new stress tolerant crops (see WP4). We will work with our collaborators at IRRI, Philippines (rice) and UK (wheat with DFW and NIAB), to link our initial results in Arabidopsis with data on rice and wheat germplasm collections in the first instance. We will use our planned annual meetings for this purpose. These projects will be pursued initially via institute fellowships (e.g. Durham International visiting Fellowships) and developed as further funding opportunities (e.g. GCRF) open up.

Committee	Research Committee B (Plants, microbes, food & sustainability)
Research Topics	Crop Science, Plant Science, Systems Biology
Research Priority	X – Research Priority information not available
Research Initiative	Longer and Larger Grants (LoLas) [2007-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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