Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Metabolic functions of p53 in non-cancer pathologies (METABOP53)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: United Kingdom
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-02-01
End date: 2018-01-31
Duration (months): 60.0
Total project cost (EUR): 2437814.0
EU funding (EUR): 2437814.0
Participants: 1
Project status: CLOSED

Extensive study of the p53 protein has resulted in a detailed understanding of its role in tumour suppression, information that is being used to develop small molecule modulators of p53 that are presently under evaluation for cancer therapy. However, it has recently become clear that p53 also plays roles in aspects of human health and disease extending beyond cancer - although most of these are poorly understood. We therefore propose to investigate some of these non-cancer functions of p53, with an emphasis on the role of p53 in the regulation of metabolism, extending to an analysis of whether p53 contributes to pathologies such as diabetes and obesity. This is a pioneering project that brings p53 research into new areas, yet builds on the solid platform of existing knowledge about the regulation and function of p53. State of the art genomic, proteomic, metabolomic and imaging analyses will be used to identify the roles of p53 in the response to metabolic stress caused by nutrient deficiency or excess, and investigate how these activities balance cell survival and cell death. Models will be developed to address how these functions of p53 relate to the control of metabolism and disease in vivo. Understanding how the cellular response to metabolic stress is controlled, and identifying a role for p53 in the regulation of metabolic homeostasis has enormous potential to influence the diagnosis and treatment of disease. The proposal will help to define the role of p53 in the development of diabetes and obesity, and lay the groundwork for the investigation of a role for p53 in other pathologies, such as neurodegenerative disease, cardiovascular disease and liver disease. These studies will therefore have far-reaching impact on some of the most prominent health threats in the developed world.
Genetic and Epigenetic Regulation of Stem Cell Fate (STEMDNAFATE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: France
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-04-01
End date: 2019-03-31
Duration (months): 72.0
Total project cost (EUR): 2494400.0
EU funding (EUR): 2494400.0
Participants: 1
Project status: CLOSED

Stem cells play crucial roles in establishing and repairing tissues, yet our knowledge of their properties, how they assure organogenesis and effect regeneration in distinct physiological contexts remains limited. A major challenge in stem cell biology is investigating these cells in their natural state in vivo, and obtaining highly pure and sufficient quantities for characterisation. Skeletal myogenesis provides an excellent paradigm to investigate stem cell function and regenerative biology because of its accessibility, and its striking ability to regenerate efficiently. Futhermore, the same individual can undergo multiple rounds of muscle injury thereby permitting the long term study of stem cell turnover and homeostasis after inflicted trauma without life threatening consequences or complex surgical procedures. The objective of this research programme is to identify mouse stem cell properties and understand how they regulate cell fate choice in different contexts by modulating their modes of cell divisions. Specifically, biased DNA segregation, which has been reported in diverse organisms from bacteria to vertebrates and is thus an evolutionary ancient phenomenon, will be investigated. Notably, we developed genetic tools that allow us to isolate prospectively those cells that execute asymmetric vs. symmetric cell divisions during regeneration, and directly linked cell fates with biased DNA segregation. The use of innovative nucleotides, micropatterns to mimic the niche, epigenetic, genetic and single cell transcriptomics strategies comprise a multi-pronged strategy to uncover the underlying mechanisms that govern asymmetric cell fates and biased DNA segregation. This knowledge will be projected to tissuegenesis using complementary clonal lineage tracing and live imaging of cell divisions in vivo. These studies aim to identify the diverse modes of stem cell divisions during tissuegenesis, information that can significantly impact on regenerative medicine.

Keywords: asymmetric cell division,template dna strand segregation,micropatterns,live imaging in mouse,skeletal muscle stem cells
Carbon dioxide regulation of Earth’s ecological weathering engine: from microorganisms to ecosystems (CDREG)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: United Kingdom,United Kingdom,United Kingdom,United Kingdom,United Kingdom
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-06-01
End date: 2018-05-31
Duration (months): 60.0
Total project cost (EUR): 2271980.0
EU funding (EUR): 2271980.0
Participants: 5
Project status: CLOSED

CDREG develops the major new Earth system science research hypothesis that tectonic-related variations in Earth’s atmospheric CO2 concentration ([CO2]a) drive negative ecological feedbacks on terrestrial silicate weathering rates that stabilise further [CO2]a change and regulate climate. This paradigm-changing hypothesis integrates ecological and abiotic controls on silicate weathering to understand how terrestrial ecosystems have shaped past Earth system dynamics. The proposed ecological feedbacks are mechanistically linked to the extent and activities of forested ecosystems and their symbiotic fungal partners as the primary engines of biological weathering. CDREG’s core hypothesis establishes an exciting cross-disciplinary Research Programme that offers novel opportunities for major breakthroughs implemented through four linked hypothesis-driven work packages (WPs) employing experimental, geochemical and numerical modelling approaches. WP1 quantitatively characterises [CO2]a-driven tree/grass-fungal mineral weathering by coupling metabolic profiling with advanced nanometre scale surface metrological techniques for investigating hyphal-mineral interactions. WP2 quantifies the role [CO2]a-drought interactions on savanna tree mortality and C4 grass survivorship, plus symbiotic fungal-driven mineral weathering. WP3 exploits the past 8 Ma of marine sediment archives to investigate the links between forest to savanna transition, terrestrial weathering, fire, and climate in Africa. WP4 integrates findings from WP1-3 into a new Earth system modelling framework to rigorously investigate the biogeochemical feedbacks of [CO2]a-regulated ecological weathering on [CO2]a via marine carbonate deposition and organic C burial. The ultimate goal is to provide a new synthesis in which the role of [CO2]a in regulating the ecological weathering engine across scales from root-associated microorganisms to terrestrial ecosystems is mechanistically understood and assessed.

Keywords: mycorrhiza,symbiosis,savanna,c4 photosynthesis,tree mortality,africa
Novel anaerobes for a biobased economy (NOVEL ANAEROBES)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Netherlands,Portugal
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-04-01
End date: 2018-03-31
Duration (months): 60.0
Total project cost (EUR): 2494592.0
EU funding (EUR): 2494592.0
Participants: 2
Project status: CLOSED

Our current society depends on many natural resources, and the availability of these natural resources (minerals, fossil fuels) is becoming more and more limited. The challenge of a sustainable and biobased economy is to develop innovative technologies to recover and reuse minerals and energy-rich compounds from waste streams and non-food agricultural crops. Microorganisms can be exploited for biotechnological purposes. The aim of this project is to study novel anaerobic microorganisms that: 1. Degrade and grow with biopolymers (polysaccharides and lipids), 2. Produce high value products (succinate and long chain fatty acids), 3. Possess a metabolism that can be steered by hydrogen and/or electricity. Microbial diversity represents an enormous reservoir of novel catalysts that can be exploited for a biobased economy. Molecular ecological research has shown that the majority (> 95 %) of the microorganisms in Nature has not yet been cultured and characterized. Their function in geochemical cycles is unknown and their biotechnological potential unexploited. This also applies for methanogenic environments in which organic matter is converted to methane and carbon dioxide, via energy rich organic intermediates. Our understanding of the microbial interactions that take place in methane formation is still scarce, especially how fermentations are influenced by hydrogen. In methanogenic environments fermentative anaerobes are present that produce valuable organic compounds, which should be exploited. Novel anaerobes can be isolated by intelligent and innovative isolation approaches, such as the MicroDish method. This method is currently adapted in my group for high throughput screening of strict anaerobes. The genomes of selected strains will be sequenced, followed by proteomics to obtain insight into their physiology to optimize the formation of valuable compounds. Such novel anaerobes will become the pillars of new biotechnological activities in Europe.

Keywords: sustainable biotechnology,methanogenic communities,biobased economy
Species range shifts, aboveground-belowground community reassembly and consequences for ecosystem functioning (SPECIALS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: Netherlands
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-06-01
End date: 2018-05-31
Duration (months): 60.0
Total project cost (EUR): 1960000.0
EU funding (EUR): 1960000.0
Participants: 1
Project status: CLOSED

Climate warming promotes intra-continental range shifts of plants, animals and microbes from lower to higher latitudes and altitudes. Plants may shift their ranges independent of their co-evolved aboveground and belowground biota, however little is known about how these communities re-assemble in the new range and how that process influences community dynamics and ecosystem functioning. Thus far, predictions on species occurrences have been based exclusively on how niche conditions shift to higher latitudes and altitudes. Here, I will make the next step towards predicting how terrestrial systems respond to climate warming by evaluating interactions between plants, aboveground and belowground multi-trophic communities in the original and new ranges. My overall aim is to determine how aboveground and belowground multi-trophic level communities become disjointed and concomitantly re-assembled during plant range shifts. I will determine consequences for community dynamics and ecosystem functioning in the new range. My overall hypothesis is that due to time-lags in range shifts between plants, and their aboveground and belowground biota, novel communities may develop in the new range that will alter functioning of ecosystems, their stability and resilience. I will study range shifting plant species and determine: 1) aboveground-belowground multi-trophic community composition, 2) specificity of soil-borne pathogens and root-feeding nematodes, arbuscular mycorrhizal fungi, and decomposer organisms, 3) bottom-up and top-down control of these biota by soil communities, and 4) dynamics, stability and resilience of original and novel communities and ecosystem functions under current and future climate conditions. My results will be the first to show how the disjunction and reassembly of aboveground-belowground communities influences plant performance, community dynamics and ecosystem functioning. This will develop a new perspective on climate warming-induced range shifts.

Keywords: terrestrial ecology,soil ecology,aboveground-belowground interactions,climate warming,range shift,multitrophic interactions,enemy release,biological invasion,soil-borne pathogens
The Biomechanics of Epithelial Cell and Tissue Morphogenesis (BIOMECAMORPH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: France
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-05-01
End date: 2018-04-30
Duration (months): 60.0
Total project cost (EUR): 2473313.0
EU funding (EUR): 2473313.0
Participants: 1
Project status: CLOSED

Tissue morphogenesis is a complex process that emerges from spatially controlled patterns of cell shape changes. Dedicated genetic programmes regulate cell behaviours, exemplified in animals by the specification of apical constriction in invaginating epithelial tissues, or the orientation of cell intercalation during tissue extension. This genetic control is constrained by physical properties of cells that dictate how they can modify their shape. A major challenge is to understand how biochemical pathways control subcellular mechanics in epithelia, such as how forces are produced by interactions between actin filaments and myosin motors, and how these forces are transmitted at cell junctions. The major objective of our project is to investigate the fundamental principles of epithelial mechanics and to understand how intercellular signals and mechanical coupling between cells coordinate individual behaviours at the tissue level. We will study early Drosophila embryogenesis and combine quantitative cell biological studies of cell dynamics, biophysical characterization of cell mechanics and genetic control of cell signalling to answer the following questions: i) how are forces generated, in particular what underlies deformation and stabilization of cell shape by actomyosin networks, and pulsatile contractility; ii) how are forces transmitted at junctions, what are the feedback interactions between tension generation and transmission; iii) how are individual cell mechanics orchestrated at the tissue level to yield collective tissue morphogenesis? We expect to encapsulate the information-based, cell biological and physical descriptions of morphogenesis in a single, coherent framework. The project should impact more broadly on morphogenesis in other organisms and shed light on the mechanisms underlying robustness and plasticity in epithelia.

Keywords: mechanics
Light-driven Chemical Synthesis using Cytochrome P450s (LIGHTDRIVENP450S)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Denmark
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-03-01
End date: 2019-02-28
Duration (months): 72.0
Total project cost (EUR): 2499699.0
EU funding (EUR): 2499699.0
Participants: 1
Project status: CLOSED

The goal of this proposed research initiative is to engineer chloroplasts into production units for high value bio-active natural products. The first aim is to re-route the biosynthetic pathways for these compounds into the chloroplast and to boost compound formation by optimizing and channeling reducing power from photosystem I into to the energy demanding steps. By these measures we aim to overcome the inherent limitations in plants to channel photosynthetic fixed carbon and reducing power directly into production of desired bioactive natural products. Our production targets are diterpenoids with the anti-cancer drug ingenol-3-angelate and the adenylyl cyclase activator forskolin as the two chosen test compounds. Formation of the complicated hydroxylated core structures of these compounds is catalyzed by diterpenoid synthases and cytochrome P450s. These will be identified and expressed in the chloroplast. The ultimate aim is to construct a single supramolecular enzyme complex effectively using solar energy to produce complex diterpenoids. This will be accomplished by tethering the terpenoid synthases and the key P450 enzymes directly to the photosystem I complex using some of the small membrane spanning subunits of photosystem I as membrane anchors. The experimental systems used will initially be transient expression in tobacco and then move to stably transformed moss (Physcomitrella patens). The production system is built on the “share your parts” principle of synthetic biology and the aim is to construct a modular ‘tool box’ as template for tailoring the synthesis of a whole range of valuable bioactive diterpenoids. Typically, these are difficult to obtain because they are produced in very low amounts in plants difficult to cultivate. The proposal opens up entirely new research horizons and removes current bottlenecks in industrial exploitation. The technology holds the promise of true sustainability as it is driven by solar power and CO2.

Keywords: photosystem i,cytochromes p450,in vitro systems,cyanobacteria,mosses,plant cell cultures
Locomotion, hunting and habitat utilisation among large African carnivores and their prey (LOCATE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: United Kingdom
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-06-01
End date: 2019-02-28
Duration (months): 69.0
Total project cost (EUR): 3079643.4
EU funding (EUR): 3079643.4
Participants: 1
Project status: CLOSED

I propose to make the first detailed measurements of the mechanics and energetic cost of locomotor activity including hunting of five large terrestrial carnivore species and their five predominant prey on the southern African savannah. We will refine and use our own innovative design of dynamically responsive tracking collar with high accuracy GPS, accelerometers, gyroscopes, and solar charged batteries to capture round the clock activity, manoeuvring and agility. We will use a geopointing camera gimble on aircraft and UAV to track collared animals and record locomotion of adjacent uncollared animals to obtain high resolution aerial video of hunting. Hunts will be overlaid on a terrain and vegetation map generated using full waveform LiDAR laser scanning and aerial photography to understand the impact of vegetation type, density and surface profile (camber and incline) on locomotion and hunt outcome. We will make detailed measurements of musculoskeletal anatomy and muscle physiology to determine tradeoffs between power and economy for each group and the extent to which hunt performance and outcome can be simply attributed to musculoskeletal physiology and fatigue in the different species. The technological innovation and integration, its application to wild animals and the massive potential for its application in field biology is all ground breaking. This would be the first investigation of hunting dynamics where every hunt, day and night of a predator is captured and analysed along with prey dynamics (in a subset) to understand what environmental factors influence outcome. It will be the first study to evaluate the extreme dynamics of highly motivated non-domestic species, their anatomy and muscle physiology and the locomotor determinants of successful and unsuccessful hunts. These data and the detailed tracking data will enable studies of terrain utilisation, intra- and inter-species conflict and the impact of vegetation change on species success and survival.

Keywords: locomotion,biomechanics,gps,animal movement
Targeting RAS oncogene addiction (RASTARGET)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: United Kingdom
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-05-01
End date: 2019-04-30
Duration (months): 72.0
Total project cost (EUR): 2496221.0
EU funding (EUR): 2496221.0
Participants: 2
Project status: CLOSED

Lung cancer is the most common type of malignant tumour worldwide and the leading cause of cancer-related death (335,000 deaths per year in Europe). The KRAS oncogene is frequently activated by point mutation in human lung cancer and mutations in the RAS family oncogenes are responsible for driving some 20% of all human malignancies. Most cell lines from RAS mutant tumours remain “oncogene addicted” to continued RAS function. There is therefore a pressing need to develop cancer therapies that target RAS. To date it has proven impossible to target the RAS proteins directly and it is unclear whether combined targeting of downstream pathways that RAS controls will prove effective. We have previously probed the unique vulnerabilities of RAS mutant cancer cells using synthetic lethal genome-wide screening approaches. This has led to the identification of a transcriptional programme controlled by GATA2 that is selectively essential for RAS mutant lung cancer cell survival. Deletion of GATA2 leads to dramatic regression of RAS induced in lung cancer in mouse models. Although GATA2 itself is likely to be undruggable, combined suppression of two GATA2 regulated pathways, ROCK and the proteasome, with clinically approved inhibitors causes marked tumour clearance. We propose to investigate the ability of these promising targeting strategies to impact on various RAS induced cancers and also to investigate mechanistic aspects of this dependency on GATA2 function. We will test the effect of GATA2 deletion or ROCK/proteasome combination therapy on RAS mutant tumour maintenance in the setting of p53 loss, both in lung and pancreatic cancer. In addition, we will determine the mechanisms involved in the dependency of RAS mutant cancers on these pathways in vivo, including investigating effects on the interaction of the tumour with host tissues, with a view to finding improved means of targeting these tumours and avoiding the development of resistance to these therapies.

Keywords: oncogene addiction,ras,synthetic lethality,mouse model,lung cancer