Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Mechanism of Unconventional Protein Secretion (MUPS)

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: Spain
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-08-01
End date: 2016-07-31
Duration (months): 60.0
Total project cost (EUR): 2206963.0
EU funding (EUR): 2206963.0
Participants: 1
Project status: CLOSED

Approximately 30% of the human genes encode proteins that enter the Endoplasmic Reticulum (ER) by a hydrophobic sequence called the signal sequence. Most of these proteins are transported to the Golgi apparatus for sorting and subsequent delivery to the endosomes, cell surface, and the extracellular space. There is good understanding of this process of ¿conventional¿ protein secretion. Surprisingly, there is another class of cytoplasmic proteins that are secreted even though they a lack signal sequence to enter the ER. How are such proteins secreted? The yeast protein a-factor achieves this goal by direct transport across the plasma membrane via an ABC transporter encoded by the STE6 gene. Little else of significance is known about this ¿unconventional¿ secretory pathway. Our new findings reveal that secretion of signal sequence lacking acyl-coA binding protein or Acb1 in Saccharomyces cerevisae and Pichia pastoris requires autophagy related genes, fusion of membranes with early endosomes, formation of multivesicular body and the plasma membrane fusion protein (t-SNARE) called Sso1p. Our results indicate that secretion of Acb1 is mediated by a secretory autophagosomes. The secretion of Acb1 therefore does not follow the same pathway as the a-factor. But how is Acb1 packed into an autophagosome and why doesn¿t the secretory autophagosome fuse with the vacuole? In other words what is the difference between a secretory and a degradative autophagosome? Does an autophagosome-like vesicle also secrete cytokines, which lack a signal sequence to enter the ER? Our aim is to address these key questions. Many unconventionally secreted proteins regulate tissue organization, behavior (anxiety and addiction), angiogenesis, immune surveillance and diabetes. Understanding the mechanism of this poorly understood process is therefore of fundamental importance.

Keywords: protein secretion,unconventional secretion
International Partnership for Advanced Coatings by Thermal Spraying (IPACTS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Research Staff Exchange Scheme
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France,United Kingdom,United Kingdom
Call:  (FP7-PEOPLE-2010-IRSES, 2010)
Start date: 2011-09-01
End date: 2015-08-31
Duration (months): 48.0
Total project cost (EUR): 705600.0
EU funding (EUR): 705600.0
Participants: 3
Project status: CLOSED

IPACTS will develop an EU-China network for surface engineering research by uniting activities among 4 top ranking European and Chinese universities. 28 researchers will be exchanged and trained with latest techniques covering the complete cycle of thermal spraying research from coating process, structure and application. IPACTS will set the foundation stones for long-term strategic collaboration between EU and China to confront the challenge of sustainable materials and low carbon-emission manufacturing in a global framework.

Keywords: technological sciences
Mapping the life histories of T cells (LIFE-HIS-T)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Netherlands
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2017-01-31
Duration (months): 69.0
Total project cost (EUR): 2499640.0
EU funding (EUR): 2499640.0
Participants: 1
Project status: CLOSED

T cells display many different phenotypes and functions, depending on the nature of previously encountered signals. If we want to understand how these different T cell subsets arise, we need to be able to follow individual T cells and their progeny through time. With the aim to map the life histories of individual T cells we have developed unique technologies that allow us to determine whether different T cell populations arise from common or distinct progenitors. Within this project we will utilize genetic reporter systems to determine: 1. How T cell recruitment, proliferation and death shape antigen-specific T cell responses 2. At which stage the resulting T cells commit to the effector or the memory T cell lineage 3. The self renewal potential of the tissue-resident memory T cells that remain after infection is cleared By following T cells and their progeny through time, this project will describe the regulation of cell fate in antigen-specific T cell responses. Furthermore, this project will lead to the creation of novel reporters of cellular history that will be of broad value to analyze cell fate and kinship for a variety of cell types.

Keywords: lineage tracing,genetic tagging
Experimental Research into Ageing (ERA)

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: Germany
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2489200.0
EU funding (EUR): 2489200.0
Participants: 1
Project status: CLOSED

The diseases of older age are a major challenge to human societies. Despite the complexity of ageing, both reduced food intake (dietary restriction) and simple genetic alterations can greatly increase lifespan and provide broad-spectrum protection against diseases of ageing in laboratory animals. Furthermore, there is strong evolutionary conservation of mechanisms. For instance the nutrient-sensing insulin/IGF and TOR signalling network modulates lifespan in yeast, invertebrates and rodents. There is thus a major scientific opportunity to use model organisms to discover how to ameliorate ageing and hence to protect against ageing-related disease in humans. Our recent findings on dietary amino acid balance in the fruit fly Drosophila imply that consumption of nutrients irrelevant to metabolism is life-shortening. Using a novel genomic approach, we shall determine if the same is true in mice and measure the role of dietary imbalance in extension of lifespan by dietary restriction. Late life dietary restriction in invertebrates can increase future survival as much as permanent restriction, implying that chemical mimetics administered late in life could also be fully effective. We shall determine if dietary restriction in mice has similarly acute effects, and use dietary switches to identify candidate mechanisms of increased health and lifespan. Recent evidence has pointed to particular components of nutrient-sensing pathways as promising drug targets for prevention of age-related disease, and we shall investigate two candidates. The work will break new ground in understanding how ageing is modulated by diet and signaling pathways and point to interventions that could protect against the effects of ageing to reduce the burden of ageing-related disease in humans.
GEnetic NEtworks as a tool for anti-CAncer Drug Development (GENECADD)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Sweden
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-03-01
End date: 2016-02-29
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 2
Project status: CLOSED

Although several therapies target cellular pathways, current small molecules drug discovery is based on identification of inhibitors to single proteins, without knowledge of whether they are the most advantageous target. The objective of this proposal is to develop a novel method for drug discovery, combining phenotypic cell based screens with functional genetic networks to determine the molecular mechanisms of numerous small molecule inhibitors. This method will enable identification of numerous distinct inhibitors of a particular pathway, as well as providing their molecular mechanism. Cancer cells harbour gene mutations that make them more reliant on other cellular pathways for survival. Such cellular pathways can be targeted to selectively kill the cancer cells using the concept of synthetic lethality. In this project we want to identify inhibitors of homologous recombination to target cancer using synthetic lethality. To establish a functional genetic network for homologous recombination, we will first identify all recombination proteins using multiple genome-wide RNAi screens. Then the synthetic sick or lethal interaction map between all recombination proteins is determined by co-depletion of these. Such synthetic sick or lethal network will identify numerous putative targets for anti-cancer treatment. Importantly, using this network for chemical-genetic functional interactions will assist in determinating of the molecular mechanisms of inhibitors. Chemical-genetic networks based on synthetic sickness or lethality can potentially change future drug discovery methods as well as providing new mechanistic insights into the field of toxicology.

Keywords: synthetic lethality,cancer drug discovery,functional genetic networks
THE ENDOCYTIC AND CYTOSKELETAL MATRIX IN THE PLASTICITY OF TUMOR CELL INVASION AND MIGRATION (THE METAENDOMATRIX)

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: Italy
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-08-01
End date: 2016-07-31
Duration (months): 60.0
Total project cost (EUR): 2232200.0
EU funding (EUR): 2232200.0
Participants: 1
Project status: CLOSED

Tumor cells can adopt different modes of cell motility. The ability to switch between diverse modes of migration enables tumors to adapt to micro-environmental conditions and to metastasize. The critical pathways and cellular processes underlying the plasticity of tumor cell motility have only begun to be identified. Endocytosis, originally thought of as a device to internalize nutrients and membrane-bound molecules, is emerging as a connectivity infrastructure (which we call "the Endocytic Matrix") of different cellular networks necessary for the execution of various cellular programs. A primary role of the Endocytic Matrix is the delivery of space- and time-resolved signals to the cell, and it is thus essential for the execution of polarized functions during cell migration. The molecular mechanisms it uses are, however, ill defined and likely to involve, in addition to extranuclear pathways, also transcriptional programs. In this respect, we have acquired evidence that components of the Endocytic Matrix require de novo gene expression to promote the transition in the mode of tumor cell motility. We propose to identify critical components of the Endocytic Matrix that by controlling the cellular location of actin remodellers promote the plasticity of tumor cell migration. We will also test whether, in addition to the immediate epigenetic/signalling-based control of migration, the Endocytic Matrix regulates transcriptional programs required for the acquisition or maintenance of diverse modes of motility. Finally, in view of the key role of microRNAs (miRNAs) in cancer, we will use miRNA profiling, together with endocytic cell migration and invasion assays in human cancer cells to test whether miRNAs mediate the relationship between endocytosis and motility programs.

Keywords: endocytosis and recycling,actin dynamics,3d tumor cell migration and invasion
Transcriptional regulation of endothelial blood brain barrier differentiation by Wnt signaling (WNT FOR BRAIN)

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: Italy
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-08-01
End date: 2016-07-31
Duration (months): 60.0
Total project cost (EUR): 2390200.0
EU funding (EUR): 2390200.0
Participants: 1
Project status: CLOSED

The brain vasculature has evolved to protect the central nervous system from the constantly changing milieu in the blood stream. Endothelial cells of brain capillaries form the so called blood brain barrier (BBB), an active permeability barrier and transport system which allows a selective passage of nutrients from blood to the nervous tissue. The continuous cross talk of endothelial cells, pericytes and nervous cells influences many vascular functions and determines and maintains the BBB characteristics after birth. Our limited knowledge of the nature of these signals prevents effective therapy of several diseases such as hemorrhagic stroke or brain edema. Furthermore, the development of tools to reversibly ¿open¿ the barrier would strongly improve drug delivery to the brain. In the present project we propose to tackle the problem by studying the transcriptional mechanisms which direct BBB differentiation. This strategy is based on preliminary work which shows that the cross talk between nervous cells and the endothelium is mediated by Wnt factors and downstream beta-catenin transcriptional activity. The understanding of the mechanism of action of Wnt signaling on brain endothelium may yield novel strategies and tools for modulating BBB permeability. The project is divided in three related objectives: 1) to define the mechanism of action and downstream partners of Wnt in brain angiogenesis and BBB differentiation; 2) to use this knowledge to develop an optimized BBB model in vitro and in vivo; 3) to test whether modulation of Wnt signaling may have a therapeutic impact in the regulation of BBB in pathological conditions.

Keywords: endothelial cells,wnt,notch,sox17,stroke,angiogenesis
Programmed and unprogrammed genomic rearrangements during the evolution of yeast species (CHROMARRANGE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Ireland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 1516960.0
EU funding (EUR): 1516960.0
Participants: 2
Project status: CLOSED

By detailed evolutionary comparisons among multiple sequenced yeast genomes, we have identified several unusual regions where our preliminary evidence suggests that previously unknown molecular biology phenomena, involving rearrangement of genomic DNA, are occurring. I now propose to use a combination of dry-lab and wet-lab experimental approaches to characterize these regions and phenomena further. One region is a 24-kb section of chromosome XIV that appears to undergo recurrent 'flip/flop' inversion between two isomers at a fairly high rate in five species as diverse as Saccharomyces cerevisiae and Naumovia castellii, leading to a 1:1 ratio of the two isomers in each species. We hypothesize that this region is the site of a programmed DNA rearrangement analogous to mating-type switching. We have also identified two new genes related to the mating-type switching endonuclease HO, but different from it, that are potentially involved in rearrangement processes though not necessarily the inversion described above. We will determine the sites of action of these endonucleases. Separately, we have found evidence for a process of recurrent deletion of DNA from regions flanking the mating-type (MAT) locus in all yeast species that are descended from the whole-genome duplication (WGD) event, causing continual transpositions of genes from beside MAT to other locations in the genome. In related computational work, we propose to investigate an hypothesis that evolutionary loss of the MATa2 transcriptional activator may have been the cause of the WGD event.

Keywords: comparative genomics,genome evolution
Regulation of cell growth and division by selective degradation mechanisms (RUBINET)

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: Switzerland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2426976.0
EU funding (EUR): 2426976.0
Participants: 1
Project status: CLOSED

Cell growth and division are tightly regulated by phosphorylation and selective degradation of cellular components. Whereas autophagy is mainly responsible to eliminate long-lived proteins and organelles, the ubiquitin-proteasome system (UPS) rapidly degrades proteins when fast adaptation is needed. Defects in these degradation systems accounts for numerous human diseases, including cancer, muscle dystrophies, viral and bacterial infections and neurodegeneration. While rapid progress has been made in the identification of UPS and autophagy components, little is known about their regulation and the molecular mechanisms that ensure substrate specificity. We therefore propose an interdisciplinary combination of biochemistry, cell and structural biology, genetics, RNAi-screening, quantitative microscopy and microfluidic technology to tackle these questions in yeast and mammalian cells. E3 ubiquitin ligase complexes are important UPS components that specifically bind substrates via dedicated adaptors. In particular, cullin-based E3-ligases control cell growth and division, but much needs to be learned about their regulation and the identity and function of their key substrates. Moreover, we uncovered a function of RING-H2 E3-ligases in MAP-kinase networks, providing a new link between phosphorylation and the UPS. Finally, while autophagy can selectively remove protein aggregates and damaged or excess organelles, the underlying mechanisms that provide specificity to this process are poorly understood. Recent evidence suggests that ubiquitin may also serve as a recognition signal for selective autophagy. We will thus investigate the roles of ubiquitin and specific autophagy substrate-adaptors, and focus on the molecular crosstalk between selective autophagy and the UPS.

Keywords: mitosis,replication,growth control,map kinase signaling,selective autophagy,ubiquitin
A North-South-Network on Urban Self-Organisation and Public Life in Europe, India and China (URBANSELF)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Research Staff Exchange Scheme
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany,Portugal,Netherlands,Hungary
Call:  (FP7-PEOPLE-2010-IRSES, 2010)
Start date: 2011-07-01
End date: 2014-06-30
Duration (months): 36.0
Total project cost (EUR): 222600.0
EU funding (EUR): 222600.0
Participants: 5
Project status: CLOSED

URBANSELF - A North-South-Network on Urban Self-Organisation and Public Life in Europe, India and China builds on existing contacts of cooperative research and knowledge exchange. The objective of URBANSELF is to bring together and integrate competences on urban processes in Europe, India and China with a specific focus on urban self-organisation and how this can contribute to the development and enhancement of public dialogue within and between the three participating areas. Thus as well as seeking to further the role of civil society within Europe, India and China, URBANSELF intends to strengthen the North–South dialogue. In the “urban age” this is of particular relevance, because urban problems are increasingly global challenges and it is vital to share knowledge and understanding of these challenges and how to address them. The bringing about of change in governance, policy and politics aimed at enhancing the role of the citizens, and their self-organising activities, will facilitate the rise of organisations that enable the articulation of interests and the creation of supporting socio-economic practices. Accordingly, urban governance has to interface with these citizen-based organisations. The support of self-organisation is the crucial process for such a transition towards real citizen participation. Consequently, self-organisation is a necessity for urban sustainability. The key objective is to understand these forms of organisation through comparative discussion and knowledge transfer of existing research on European cities and rapidly growing cities in India and China. This then allows for empirically founded theoretical conclusions which in turn will provide the basis to identify innovative approaches to urban challenges from an actor-oriented perspective. The scientific results of urban self-organisation and associated developments in the public sphere will be addressed to the relevant stakeholders (local organisations, administration, and politician)

Keywords: humanities,urban governance,urban policy,deprived urban areas,public urban sphere,urban self-organisation
Protective and pathogenic immunological memory and its organisation by stroma cells (IMMEMO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Germany
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-08-01
End date: 2016-07-31
Duration (months): 60.0
Total project cost (EUR): 2465000.0
EU funding (EUR): 2465000.0
Participants: 1
Project status: CLOSED

Immunological memory provides immunity against recurrent pathogens, but also can induce and regulate immunopathology. In chronic immune-mediated diseases, a "pathogenic" immunological memory probably is the essential driver of inflammation, refractory to physiological regulation and state-of-the-art therapeutic immunosuppression, and thus a challenge for the development of novel, curative therapeutic strategies. Despite its relevance, immunological memory is poorly understood. We recently discovered memory plasma cells and professional memory T helper cells, and their organisation by bone marrow stroma and the stroma of inflamed tissues. We have identified genes and regulating function and persistence of memory and effector cells in the resting state and in chronic immune reactions. Based on these intriguing, paradigm-breaking initial results, I propose to develop and lead a research program addressing the organisation and role of immunological memory in protective immunity and in immune-mediated diseases, on the systemic, cellular and molecular level. In particular, I propose to (1) analyse the homing of plasmablasts and T helper memory cell precursors to dedicated survival niches of the bone marrow or inflamed tissues, (2) identify the niches of CD8 memory cells and memory B cells, (3) analyse the cellular and molecular composition of memory niches, (4) decipher the molecular communication between stromal cells and immune memory cells, (5) analyse how memory/effector T helper cells are reactivated, (6) define the role of memory-phenotype T cells in the periphery, (7) analyse the role of twist1 and hop for persistence and function of pathogenic Th memory/effector cells, and (8) develop strategies to selectively delete pathogenic immune memory cells.

Keywords: chronic inflammation,bone marrow,plasma cells,memory lymphocytes