Final Report Summary - MERIT (Metabolic Reprogramming by Induction of Transcription)
Acquisition of energy and regulation of its use by different metabolic pathways is the fundamental basis for life on earth. Energy is generally scarce and living organisms have to either feed on other organisms or use photosynthesis to generate the energy-rich compounds needed to sustain growth and development. Energy supplies vary over time and all eukaryotes have evolved methods to store energy rich molecules. This enables them to counteract adverse conditions as availability that can be buffered via storage reserves. In all organisms energy usage is modulated by central and conserved signal transduction pathways regulating both the rate of energy usage and storage as well as the rate of energy capture (feeding or photosynthesis). When a plant or other eukaryotic organism faces a situation with limited energy availability then storage reserves are mobilized and energy-consuming activities (including growth) are inhibited. The ability to restrict energy usage is central for survival. To avoid the detrimental effects of prolonged starvation a large scale reprogramming of metabolism occurs. This involves repression of biosynthetic activities and the induction of catabolic processes to generate the needed nutrients. This process is tightly linked to the repression of growth as well. We name this response the low energy syndrome, LES.
In January 2011 MERIT started as a consortium of 7 beneficiaries from 6 countries (NL, DE, AT, SP, PT, BE) and 1 associated partner (Nunhems, NL). Umea University was added in January 2012 as an associated partner to expend the scientific and training program for the MERIT fellows. 10 Early Stage Researcher projects and 2 Experienced Researcher projects were executed. To achieve the objectives the scientific activities and training activities were divided into 6 Work Packages (WP). Each ESR and ER has investigated specific research questions (projects), which were embedded in a scientific framework within the consortium. The training was organized in local training, network training, and external network–related training. A wide range of methodology was deployed ranging from classical physiology to state-of-the-art mass spectrometry based protein and metabolite profiling, massive sequencing of immuno-precipitated chromatin and whole genome expression profiling. This was further supported by bioinformatic approaches, phylogenetical as well as network based. The aim was to understand the mechanisms regulating energy balance in plants and their impact on plant performance under stress. Improved stress tolerance of plants is of strategic importance in a world with rising population and changing climate. This strategic importance as well as future recruitment possibilities motivated the high involvement of industrial partners in the proposed activities. The consortium got external input from the Scientific Advisory Board. Members of the SAB were Prof. Julia Baley–Serres (University of California), Prof. Christine Foyer (University of Leeds), and Dr. Michael Metzlaff (Bayer CropScience). All of them are international experts on this field. They were assessing the progress of the project and gave external advice.
The primary scientific goal of MERIT was to understand the mechanism of regulating the Low Energy Syndrome (LES). This has been achieved in molecular detail. The partners within MERIT were able to identify key regulatory steps and transcriptional control nodes regulating LES. The project has generated many useful tools and insights to provide better use of plant genomics data, especially on transcriptomics data, proteome sequence data, and translatome data. All findings are relevant for breeding crops to improve yield and stress resistance. In some cases this knowledge has also been transferred to non-Arabidopsis plants (e.g. poplar) so more commercial aspects can be investigated. Genetic material has been generated in sufficient amounts to start critical experiments regarding to yield optimization. Regarding the SnRK1 kinase significant progress has been achieved on the understanding of regulatory mechanisms by regulatory phosphatases. One SnRK1 transcription factor target is as well identified in bZIP63 and the regulatory mechanism of SNRK1 dependent bZIP53 activation is partly elucidated. This related to the progress in WP2 were the dimerizing properties of S1/C bZIP transcription factors have been mapped and shown to be dependent on SnRK1 and other metabolic signals. Several targets of the transcription factor dimers both related to metabolism and other processes including seed biology, hormone signaling and senescence have been identified. In several cases are knock downs of bZIP target genes identified and several of the metabolic and developmental phenotypes of bZIP mutants and overexpressors can be explained by changes in the activities of these target genes. Metabolic phenotypes of plants affected in bZIP or SnRK1 activity have been extensively studied including a large (two thousand samples) experiment with the combined genetic material from the whole network. Also the specific metabolic phenotypes of individual lines have been analysed and a picture of overlapping activities regulating amino acid metabolism and glycolysis/TCA cycle emerged. The genetic material mentioned above have also been profiled in the automatic phenotyping platform and many of the lines tested have mild to severe growth pattern changes, especially in combination with stress (energy starvation, salt treatments, etc.). The scientific success is mirrored by the outcome of MERIT. In total almost 40 peer–reviewed publications are already published or planned in which many of the individual groups are part, including ESRs and ERs. Here is the publication of Tomé et al. (2014) a good example. Starting as an element in the scientific writing course CST3/4 the joint effort resulted in a paper late 2014 and is already cited. More than 50 contributions (oral and posters) to international events outside the MERIT network were counted only by the fellows.
In summary the picture envisaged in the MERIT proposal, is proven to be correct and has gained significant amount of mechanistic detail. MERIT made special progress in understanding SnRK1 regulation by upstream proteins, bZIP activation and target gene regulation and metabolic reprogramming. There are still changes ahead we need to know, e.g. how plants sense low energy and how the changed metabolism affects growth. The consortium will address these issues in the future, because it became clear during the project that the group of researchers that have been part of MERIT will continue collaborative efforts. A joint proposal has been submitted already.
The website (http://theory.bio.uu.nl/MERIT/html/index.html(opens in new window)) was set up at the beginning of the project and maintained by the project coordinator. It served as a central platform and ensured the dissemination of project relevant information.
For further information, please refer to the network coordinator.
Dr. Johannes Hanson
Utrecht University
email: s.j.hanson@uu.nl
In January 2011 MERIT started as a consortium of 7 beneficiaries from 6 countries (NL, DE, AT, SP, PT, BE) and 1 associated partner (Nunhems, NL). Umea University was added in January 2012 as an associated partner to expend the scientific and training program for the MERIT fellows. 10 Early Stage Researcher projects and 2 Experienced Researcher projects were executed. To achieve the objectives the scientific activities and training activities were divided into 6 Work Packages (WP). Each ESR and ER has investigated specific research questions (projects), which were embedded in a scientific framework within the consortium. The training was organized in local training, network training, and external network–related training. A wide range of methodology was deployed ranging from classical physiology to state-of-the-art mass spectrometry based protein and metabolite profiling, massive sequencing of immuno-precipitated chromatin and whole genome expression profiling. This was further supported by bioinformatic approaches, phylogenetical as well as network based. The aim was to understand the mechanisms regulating energy balance in plants and their impact on plant performance under stress. Improved stress tolerance of plants is of strategic importance in a world with rising population and changing climate. This strategic importance as well as future recruitment possibilities motivated the high involvement of industrial partners in the proposed activities. The consortium got external input from the Scientific Advisory Board. Members of the SAB were Prof. Julia Baley–Serres (University of California), Prof. Christine Foyer (University of Leeds), and Dr. Michael Metzlaff (Bayer CropScience). All of them are international experts on this field. They were assessing the progress of the project and gave external advice.
The primary scientific goal of MERIT was to understand the mechanism of regulating the Low Energy Syndrome (LES). This has been achieved in molecular detail. The partners within MERIT were able to identify key regulatory steps and transcriptional control nodes regulating LES. The project has generated many useful tools and insights to provide better use of plant genomics data, especially on transcriptomics data, proteome sequence data, and translatome data. All findings are relevant for breeding crops to improve yield and stress resistance. In some cases this knowledge has also been transferred to non-Arabidopsis plants (e.g. poplar) so more commercial aspects can be investigated. Genetic material has been generated in sufficient amounts to start critical experiments regarding to yield optimization. Regarding the SnRK1 kinase significant progress has been achieved on the understanding of regulatory mechanisms by regulatory phosphatases. One SnRK1 transcription factor target is as well identified in bZIP63 and the regulatory mechanism of SNRK1 dependent bZIP53 activation is partly elucidated. This related to the progress in WP2 were the dimerizing properties of S1/C bZIP transcription factors have been mapped and shown to be dependent on SnRK1 and other metabolic signals. Several targets of the transcription factor dimers both related to metabolism and other processes including seed biology, hormone signaling and senescence have been identified. In several cases are knock downs of bZIP target genes identified and several of the metabolic and developmental phenotypes of bZIP mutants and overexpressors can be explained by changes in the activities of these target genes. Metabolic phenotypes of plants affected in bZIP or SnRK1 activity have been extensively studied including a large (two thousand samples) experiment with the combined genetic material from the whole network. Also the specific metabolic phenotypes of individual lines have been analysed and a picture of overlapping activities regulating amino acid metabolism and glycolysis/TCA cycle emerged. The genetic material mentioned above have also been profiled in the automatic phenotyping platform and many of the lines tested have mild to severe growth pattern changes, especially in combination with stress (energy starvation, salt treatments, etc.). The scientific success is mirrored by the outcome of MERIT. In total almost 40 peer–reviewed publications are already published or planned in which many of the individual groups are part, including ESRs and ERs. Here is the publication of Tomé et al. (2014) a good example. Starting as an element in the scientific writing course CST3/4 the joint effort resulted in a paper late 2014 and is already cited. More than 50 contributions (oral and posters) to international events outside the MERIT network were counted only by the fellows.
In summary the picture envisaged in the MERIT proposal, is proven to be correct and has gained significant amount of mechanistic detail. MERIT made special progress in understanding SnRK1 regulation by upstream proteins, bZIP activation and target gene regulation and metabolic reprogramming. There are still changes ahead we need to know, e.g. how plants sense low energy and how the changed metabolism affects growth. The consortium will address these issues in the future, because it became clear during the project that the group of researchers that have been part of MERIT will continue collaborative efforts. A joint proposal has been submitted already.
The website (http://theory.bio.uu.nl/MERIT/html/index.html(opens in new window)) was set up at the beginning of the project and maintained by the project coordinator. It served as a central platform and ensured the dissemination of project relevant information.
For further information, please refer to the network coordinator.
Dr. Johannes Hanson
Utrecht University
email: s.j.hanson@uu.nl