Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Regulation of the Hippo tissue growth pathway by nutrient sensing mechanisms in Drosophila melanogaster (HIPPOGAILITE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-04-01
End date: 2015-03-31
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The Hippo pathway is a highly conserved tumour suppressor pathway that restricts cell proliferation and promotes apoptosis. Although initially discovered in Drosophila, the Hippo pathway is highly conserved in mammals. Mutations and epigenetic silencing of Hippo pathway genes are frequently found in cancer tissues. Thus, our understanding of pathway regulation is important for the understanding of tumour formation and potential cancer treatments. The upstream regulation of the Hippo pathway is complex, but until now not completely understood. In the host lab, Salt-inducible kinases (SIKs) were identified as inhibitors of the Hippo pathway. SIKs belong to the AMP-activated protein kinase (AMPK) family. AMPK family kinases are sensors of nutrient or energy status. Thus, SIKs might activate cell growth in conditions of optimal nutrient availability, thereby coupling developmental growth with nutritional status. In the proposed project I plan to investigate whether and how nutrient and energy levels regulate SIKs in context of Hippo signalling. Additionally, I will test whether other AMPK family kinases are involved in regulation of the Hippo pathway. I will use a multidisciplinary approach that encompasses whole organism nutritional assays, Drosophila genetic manipulation, cell biology, biochemistry and state-of-art imaging techniques. The goal of the project is to elucidate the coupling between nutrient sensing and Hippo signalling. Since altered metabolism and nutrient usage is a feature of cancer cells, I believe this work will advance our understanding of oncogenic transformation. This year, the first attempts at designing cancer treatments that target the Hippo pathway in cancer tissues have emerged. Full knowledge of the details of Hippo pathway regulation will be required for a successful choice of targets and pharmacological compounds, to appreciate potential side effects and to predict the effect of currently used drugs on the Hippo pathway.

Keywords: hippo,drosophila,cell proliferation,nutrient sensing,ampks,salt-inducible kinases
Single-cell phylogenomic exploration of archaeal dark matter (DARKCELLS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Sweden
Call:  (FP7-PEOPLE-2012-IIF, 2012)
Start date: 2014-04-01
End date: 2016-03-31
Duration (months): 24.0
Total project cost (EUR): 197811.6
EU funding (EUR): 197811.6
Participants: 1
Project status: CLOSED

While the archaeal domain of life was discovered more than 30 years ago, the biology of archaeal organisms remains to be relatively obscure, especially when compared to that of bacterial and eukaryotic life. Yet, despite the limited knowledge regarding their lifestyle and ecological relevance, evidence is mounting that certain archaea play key roles in global nitrogen and carbon cycles. In addition, archaea share a common branch in the tree of life with the eukaryotes, and have most likely played a prominent role in the emergence of the eukaryotic cell, and thus of complex life. Interestingly, recent ecological surveys have started to reveal a hidden diversity of archaeal life. The exploration of this supposed ‘archaeal dark matter’ might thus hold relevance for a number of fundamental issues and reveal profound insights about the diversity, ecology and evolution of the archaeal domain of life. Unfortunately, characterization of these uncultured lineages is procrastinated by limitations in cultivation techniques and limited availability of genetic tools, urging for the exploration of alternative strategies to do so. Here I am proposing to utilize a single-cell phylogenomics approach to explore novel archaeal lineages at the genomic level. Habitats hosting novel archaea will be sampled and single-cell genome sequencing will be performed using next-generation sequencing technology. The proposed strategy will result in (1) obtaining a better sampling of archaeal genomes, (2) gaining insight in the evolutionary history of the archaeal domain of life through phylogenomics, and (3) obtaining information regarding the biology and lifestyle of these novel archaeal lineages. This work will dramatically increase the number of archaeal genomes available in public databases for both researchers studying the physiology of archaea in different environments and also for evolutionary biologists tracing the evolutionary history of the three domains of life.

Keywords: genomics,comparative genomics,microbiology,ecology,evolution,bioinformatics
The crustacean chemosensory system: Consequences of climate and environmental change (CRUCSCHANGE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Sweden
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-08-01
End date: 2015-10-06
Duration (months): 24.0
Total project cost (EUR): 206350.8
EU funding (EUR): 206350.8
Participants: 1
Project status: CLOSED

Although the ability to detect and respond to chemical cues is essential in most animals, we know very little of how the chemical sense will be affected by the rapid environmental changes we face today. The overall goal of this research project is to provide improved understanding of the combined impacts of climate change and pollutants on the chemosensory system of marine organisms, focusing on ecologically and economically important crustaceans. Using a combination of behavioural investigations and electrophysiological techniques will identify interference with the chemosensory system on all levels from neuron to behaviour. The project is divided into three objectives: - To study impacts of multiple stressors from climate change (ocean acidification, temperature and salinity) and pollutants on chemically mediated behaviour, such as feeding, establishment of dominance status and mating. - To identify impacts of multiple stressors on odour detection, performing electrophysiological studies. - To investigate the plasticity of the chemosensory system and its ability to adapt to environmental change, using Idothea baltica populations locally adapted fully marine or brackish waters in reciprocal transplant experiments. The results from this project will help us identify risks and better predict consequences of climate change and will be important assessment criteria for policymakers and authorities when developing coastal management, mitigation strategies and legislation. The high complementarity of the research training will expand my scientific competence and allow me to establish my very own, unique research profile. I will learn and test new approaches and bring together competence and collaborative work from different scientific fields and countries. Thus, this research project will be a significant step in my research career in order to reach a mature, independent research position.

Keywords: climate change,chemosensory system,crustaceans,pollutants,adaptation,chemical cues,foraging,mating,v306 environmental and marine biology,v301 animal behaviour,l508 behavioral neuroscience
Control of imitation and social cognition: the interaction of motor mirroring and Theory of Mind (MIRRORING AND TOM)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Belgium
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2014-01-01
End date: 2015-12-31
Duration (months): 24.0
Total project cost (EUR): 169800.0
EU funding (EUR): 169800.0
Participants: 1
Project status: CLOSED

Recent work based on ideomotor theory and the discovery of the mirror neuron system has suggested that the observation of an action is associated with the activation of the corresponding motor representation in the observer. In accordance with this hypothesis it has been demonstrated that observing an action interferes with one’s own actions when these are different from those being observed. This, however, raises the question how we avoid automatic imitation? More specifically, how can we distinguish the motor program activated by our intention from that triggered by observation? Recent neuroimaging studies have revealed that the control of automatic imitative responses leads to activation in the anterior medial prefrontal cortex and the temporo-parietal junction. These areas are core regions of a network involved in higher-order abilities in social cognition, such as mentalizing (i.e., the ability to reflect on other people’s mental states). Based on such brain imaging results, it has been hypothesized that the control of shared representations draws on the interaction between these "social" brain regions and the mirror system. The proposed study aims to understand how high-level cognitive functions and motor mirroring interact at a neural level in the control of imitative behaviour and to explore the functional overlap between the control of shared representations and implicit forms of mentalizing. The research place itself at the interface between the research on motor control and social neuroscience and wants to integrate knowledge developed in different domains. With these objectives in mind, the applicant will conduct a series of studies by combining different methodological approaches and techniques, such as brain stimulation techniques and neuroimaging, and use state-of-the-art computational tools, such as multi-voxel pattern analysis to analyze neuroimaging data.

Keywords: mirror system,theory of mind,brain stimulation,neuroimaging,social neuroscience
The development of hypoxia-activated probes for imaging and therapy (HYPOXPROBE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2012-IIF, 2012)
Start date: 2013-11-01
End date: 2015-10-31
Duration (months): 24.0
Total project cost (EUR): 231283.2
EU funding (EUR): 231283.2
Participants: 1
Project status: CLOSED

Solid tumours contain hypoxic cells, which exist at a low oxygen tensions and are resistant to chemotherapy and radiotherapy. Although problematic for therapy, any quality that distinguishes tumour cells from healthy ones presents an opportunity for targeting therapies. We have begun developing prodrugs that selectively release inhibitors of cancer-related enzymes under hypoxia. In this project, we will develop hypoxia-activated inhibitors of the checkpoint kinase, Chk1, which is an important chemotherapeutic target. Allowing targeting of this compound to tumour cells. In addition, to enable imaging of hypoxic tumours we will develop novel hypoxia-activated fluorescent probes. The 2-nitroimidazole-based pimonidazole is a standard hypoxia-imaging agent. Pimonidazole binds cellular thiols under hypoxic conditions but the spatial resolution of imaging is poor. To improve the imaging resolution, we will develop a fluorogenic hypoxia-activated protecting group that will become fluorescent upon release of the active compound. This will provide a read-out of when and where the active compound is delivered, and fill also find application in the general imaging of hypoxia. We then aim to apply this technology to developing hypoxia-activated inhibitors of the cAMP response element binding protein binding protein (CREBBP) bromodomain. CREBBP is a histone acetyl transferase involved in regulating transcription; it has ~400 interacting protein partners making it a key node in the mammalian protein-protein interactome. One partner is hypoxia-inducible factor-1α (HIF-1α), which is a transcription factor that responds to changes in cellular oxygen levels. Given the large number of CREBBP interacting partners it is preferable to target the CREBBP bromodomain inhibitor using a hypoxia-activated group. In this way it will be possible to ascertain the role of the CREBBP bromodomain in hypoxic tumours.

Keywords: c134 biological chemistry,c141 organic chemistry
Systemic analysis of chromatin-regulatory genes in PDAC using advanced in vivo RNAi (EPI-TARGETS IN PDAC)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Austria
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-07-01
End date: 2015-06-30
Duration (months): 24.0
Total project cost (EUR): 186783.6
EU funding (EUR): 186783.6
Participants: 1
Project status: CLOSED

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death and has the lowest survival rate of all major cancers (3-5%). Despite our advanced understanding of disease pathology and underlying genetics, there are no effective chemotherapeutic or targeted treatment options, and the median survival time remains unchanged at only 6 months. PDAC arises from complex and heterogeneous genetic aberrations, which in a single case typically involve >50 genes. Besides four hallmark mutations affecting KRAS, TP53, CDKN2A and SMAD4, aberrations of the chromatin regulatory machinery are common in PDAC. Chromatin-associated genes are particularly attractive as drug targets, since resulting epigenetic aberrations are reversible and often amendable to drug-based modulation. However, the mechanistic role of chromatin aberrations, as well as their potential as therapeutic targets have not been explored in PDAC. In order to accelerate the search for more effective therapies for this devastating disease, this project will combine genetically engineered PDAC mouse models, multiplexed RNAi screening and advanced in vivo RNAi technologies to systematically analyze chromatin-regulatory genes in tumorigenesis and maintenance of PDAC. As tractable experimental system for in vivo RNAi studies, I will generate a Tet-on competent PDAC mouse model based on endogenous KrasG12D and homozygous loss of Trp53. Following its characterization, the model will be employed in multiplexed in vitro and in vivo RNAi screens using a new chromatin shRNA library. Selected hits will be functionally characterized using innovative in vivo RNAi approaches. Overall, these studies aim to advance our mechanistic understanding of chromatin (dys)regulation in PDAC, identify new target molecules for the development of more effective therapeutic, and establish a powerful in vivo system that is generally applicable for the pre-clinical evaluation of targeted therapies in PDAC.

Keywords: pancreatic cancer,pdac,in vivo rnai,mir30,rnai screening,epigenetics,chromatin,speedy mice,cancer mouse model,gemm,oncogene,tumor suppressor,kras,p53,mll3,arid1a,brd4
Protein-engineering based approach for super-resolution imaging of nucleoporin-chromatin interactions (NUPTAG)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2014-01-01
End date: 2015-12-31
Duration (months): 24.0
Total project cost (EUR): 161968.8
EU funding (EUR): 161968.8
Participants: 1
Project status: CLOSED

Nucleoporins are major building blocks of the nuclear pore complex (NPC). In addition to their role in the nucleocytoplasmic transport, a subset of nucleoporins have additional gene regulatory roles. They can bind chromatin and chromatin modifiers, either directly at the NPC or in the nucleoplasm, leading to gene repression or activation. Due to a lack of techniques that allow mapping spatial and temporal heterogeneities of individual proteins with high precision, the molecular mechanisms underlying these phenomena are far from being understood. To overcome this, I will develop a combined protein-engineering/super-resolution approach for single amino acid targeted labelling and tracking of proteins inside the cells. This strategy is based on the translational incorporation of newly developed non-canonical amino acids (ncAAs). These ncAAs are suitable for inverse-electron-demand Diels-Alder reaction, a special type of highly selective and rapid “click-chemistry” reactions proceeding in a non-toxic and fully biocompatible way inside living cells. I will employ this technology to systematically label a set of nucleoporins and chromatin modifiers with small dyes. The high photostability of these fluorophores permits long-term imaging and will allow me to identify nucleoporin binding partners in cultured mammalian cells with nanometer resolution. This will set the stage for a technology that enables deciphering protein plasticity in vivo at the molecular level and provide novel insights into multifunctionality of nucleoporins.

Keywords: c111 method development in chemistry,c134 biological chemistry,l106 biophysics,l302 cell biology and molecular transport mechanisms,l101 molecular biology and interactions,superresolution microscopy
Engineering of Energy Efficient Extraction of Critical Materials- Application to the Processing of Niobium and Tantalum Minerals (E4-CRITMAT)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-04-01
End date: 2015-03-31
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

Current situation: European Union (EU), economic growth is threatened by the unsecure supply of materials which affect main sectors of the economy such as the energy, health and digital. Historically the main resources of such mineral are located in few countries which either suffer from weak political structure or, belong to the growing economies in which the national strategies are promoting unfair competition especially in EU, thereby smothering growth within. Research Project Objectives: The E4-Crit-Mat MC is going to explain the general principles for demonstrating environmentally clean minerals and chemicals processing, which is based on alkali roasting treatment of mineral concentrates at elevated temperatures (900oC), followed by leaching and recovery of alkali by recycling CO2 and further refining. In E4-CritMat we primarily focus on the processing of Nb and Ta minerals, as a case study because of their importance in the EU’s micro-electronics, communication, and aerospace industries. Training Objectives: 1. Technological training involving high-temperature, aqueous chemical processing and characterization techniques, 2. Training in a business environment and learning its culture including exploitation and process economics analysis at the London & Scandinavian Metallurgical co in UK, 3. Enterprise training courses and its applications in industry for technology exploitation including the patent filing and licensing, 4. Environmental aspects of process engineering in mineral industry. Impact expected: 1. Provide the MC Fellow with the tools needed to reach a professional maturity. 2. Strengthen the EU companies in the market for Critical Materials via long term relationships with Brazil and helped in reducing significant environment impact. 3. Reduce the dependence of fossil fuels in terms of chemicals and energy consumption and enhance the development of energy efficiency devices, contributing to reduce the carbon footprint in EU.

Keywords: critical materials,alkali roasting,microwave technology,hydrothermal leaching,ionic liquids,green chemistry,niobium and tantalum minerals,extraction technology,minerals processing
Control of Programmed Cell Death by Metacaspases in plants (PLANTPCDCONTROL)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2012-IIF, 2012)
Start date: 2014-05-23
End date: 2016-11-15
Duration (months): 24.0
Total project cost (EUR): 223002.2
EU funding (EUR): 223002.2
Participants: 1
Project status: CLOSED

Plant pathogens devastate crops resulting in yield losses and increasing the use of often unsustainable pesticides. Understanding the basic mechanisms of the plant immune system will increase our ability to successfully combat plant diseases, satisfying the growing needs for sustainable food production, a future challenge for European agriculture. Cell death has a central role in innate immune responses in both animals and plants. The hypersensitive response (HR) is a plant-specific form of programmed cell death (PCD) occurring at the site of attempted pathogen invasion. A tight regulation of HR is essential in order to avoid unnecessary tissue damage beyond the infection site. However, the signaling pathways leading to HR still remain ill-defined. We have recently shown that Arabidopsis metacaspases, distant homologs of animal caspases, antagonistically control pathogen-triggered HR. However, their precise mode of action, regulation and substrates remain largely unknown. With this project we will use a combination of proteomic, genetic, cell biology and biochemical approaches to dissect the mechanisms underlying PCD control by this family of proteins. Defining the first plant deathosome will be a major breakthrough in plant sciences, moving forward with knowledge that can be directly translated into agronomically relevant species. We will use a multidisciplinary approach, benefitting from transnational collaborations already established by the candidate with research groups located in Europe and the USA. A Marie Curie International Incoming Fellowship will ensure the continuity of the candidate’s high-impact research at the host institution, an emerging reference center for plant sciences in Spain. Reintegration of the candidate will complement and synergize with the expertise of the host, directly contributing to European excellence.

Keywords: molecular genetics,plant genetics,programmed cell death,hypersensitive response,plant-pathogen interactions,plant diseases,arabidopsis