Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Towards understanding and manipulation of MHC class II antigen presentation (MHC CLASS II-OMICS)

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-2009-AdG, 2009)
Start date: 2010-09-01
End date: 2015-08-31
Duration (months): 60.0
Total project cost (EUR): 2112300.0
EU funding (EUR): 2112300.0
Participants: 1
Project status: CLOSED

MHC class II molecules are crucial for specific immune responses. In a complicated series of cell biological events, they catch a peptide in the endosomal route for presentation at the plasma membrane to the immune system. At present some 20 factors have been identified as involved in the process of MHC class II antigen presentation that are potential targets for manipulating these responses as MHC class II molecules are involved in most auto-immune diseases. Defining further targets for manipulating MHC class II responses would have implications for various disease states when these can be inhibited by chemical compounds or biologicals. We have performed a genome-wide FACS-based siRNA screen for molecules affecting MHC class II expression and peptide loading. After 100.000 individual 2-color FACS analyses, we identified 276 proteins that can be functionally sub-clustered for expression and for cell biological effects. We now propose to study the cell biology of these 276 hits to elucidate the molecular and cell biological mechanisms of MHC class II antigen presentation (the MHC class II-ome). As a first step, the 276 hits are sub-clustered for effects on MHC class II transcription or cell biology. These sub-clusters may correspond to networks. We propose to validate and extend these networks by experiments by a team of scientists concentrating on the various aspects of the cell biology of MHC class II antigen presentation. A parallel chemical compound screen will be performed to identify compounds affecting MHC class II antigen presentation. By cross-correlating the biological phenotypes of compounds with those of siRNA silencing, novel target-lead combinations will be defined by reciprocal chemical genetics. Our experiments should result in a global understanding of MHC class II antigen presentation. In addition, it should reveal target-lead combinations for manipulation of MHC class II antigen presentation in infection, auto-immune disease and transplantation.

Keywords: antigen presentation/ sirna screens/ chemical genetics/ mhc class ii/ auto-immune diseases
Determining the roles of the nuclear periphery in mammalian genome function (FUNCTIONALEDGE)

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: United Kingdom,United Kingdom
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-03-01
End date: 2016-02-29
Duration (months): 72.0
Total project cost (EUR): 1701090.0
EU funding (EUR): 1701090.0
Participants: 2
Project status: CLOSED

DNA sequence and epigenetic chromatin maps are important in understanding how genomes are regulated. However, these maps are linear and do not account for the three-dimensional context within which the genome functions in the cell. The spatial organisation of the genome in the nucleus is not random and is conserved in evolution, implying that it is under functional selection. This proposal aims to determine the functional significance of positioning specific genome regions at the edge of the nucleus in mammalian cells. The nuclear periphery has conventionally been considered as a zone of inactive chromatin and transcriptional repression. Several regulatory gene loci move away from the nuclear periphery as they are activated during differentiation. Novel approaches, developed by ourselves and others, that allow genomic regions to be relocated from the centre of the nucleus to the periphery, have directly shown that proximity to the nuclear edge can down-regulate human gene expression. We propose to dissect the pathways that mediate this spatially-defined transcriptional regulation, to determine what features make certain genes susceptible to it, to establish the functional consequences of preventing gene repositioning during differentiation, and to examine defects of the periphery found in premature ageing. A neglected hypothesis is that positioning of inactive chromatin against the nuclear periphery is a mechanism to minimize DNA damage on sequences in the nuclear centre. We will determine whether mutation rate is altered when loci are repositioned towards the nuclear periphery. By experimentally remodelling the spatial organisation of the genome, this proposal goes beyond the current descriptive phase of 3D nuclear organisation, into an understanding of its functional consequences on multiple aspects of genome function. It will also aid in understanding human diseases characterised by alterations of the nuclear periphery.
The physics of Ion Coulomb Crystals: Thermodynamics, Quantum control, and Quantum Simulators. (PICC)

Framework: FP7 — Cooperation
Programme: Information and Communication Technologies
Destination: Future and emerging technologies
Action type: Collaborative project
Countries involved: Germany,United Kingdom,Denmark,Israel,Germany,Germany,Spain,Germany,Germany
Call:  (FP7-ICT-2009-C, 2009)
Start date: 2010-06-01
End date: 2013-11-30
Duration (months): 42.0
Total project cost (EUR): 3034544.0
EU funding (EUR): 2298999.0
Participants: 9
Project status: CLOSED

In the quest for the realization of quantum information processors, trapped ions occupy a prominent position. The challenge of realizing large-scale processors and quantum simulators based on ions will, however, require that one deals with more complex structures, which may include mesoscopic ordered ion ensembles, i.e., ion Coulomb crystals. In this regime, it is expected that the effect of noise will grow in importance and the control techniques, which have been so successfully applied to small numbers of ions, will be inefficient. This raises the timely issue of identifying novel and efficient strategies for controlling the quantum dynamics and manipulating the quantum state of ion Coulomb crystals. The PICC proposal represents a joint theoretical and experimental effort whose aims are (i) to identify tools for controlling ion crystals as their size is scaled up, (ii) to develop strategies for implementing controlled quantum dynamics of mesoscopic ion Coulomb crystals in a noisy environment and (iii) to explore the capability of ion Coulomb crystals as quantum simulators. The long-term vision underlying this proposal is to engineer quantum correlations and entanglement in ion Coulomb crystals in order to exploit them for technological purposes of different kinds. It is expected that this effort will pave the way for what could be the realization of the first specific-purpose, large scale quantum processors, complementing existing efforts with the alternative system of neutral atoms in optical lattices.

Keywords: scalable quantum information processing,ion trap,ion coulomb crystals,quantum simulators
Durable resistance against fungal plant pathogens (DURABLERESISTANCE)

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: Switzerland
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-04-01
End date: 2015-03-31
Duration (months): 60.0
Total project cost (EUR): 2100000.0
EU funding (EUR): 2100000.0
Participants: 1
Project status: CLOSED

Plants and their pathogens are in a constant process of co-evolution. Consequently, many of the known defense genes of plants against fungal pathogens are rapidly loosing effectiveness under agricultural conditions. However, there are examples for durable resistance. It is one of the main research questions in plant biology to determine the genetic basis of such naturally occurring resistance and to understand the underlying biochemical and molecular cause for durability. This durability is characterized by the apparent inability of the pathogen to adapt to the resistance mechanism. The molecular understanding of durable resistance will contribute to future attempts to develop such resistance by design. We want to use two approaches towards understanding and developing durable resistance: the first one is based on the naturally occurring durable resistance gene Lr34 against rust and mildew diseases in wheat. This gene was recently isolated in our group and it encodes a putative ABC type of transporter protein, providing a possible link between non-host and durable resistance. Its function in resistance will be studied by genetic and biochemical approaches in the crop plant wheat, as there is no Lr34-type of resistance characterized in any other plant. However, there is a close Lr34-homolog in rice and its function will be investigated in this diploid system. The second approach will be based on natural diversity found in a specific resistance gene, conferring strong, but not durable resistance. This diversity will be used for a designed improvement of durability by developing new proteins or protein combinations to which the pathogen can not adapt. We will use the 15 naturally occurring alleles of the Pm3 powdery mildew resistance genes to identify the structural basis of specific interactions. Based on this characterization, we will develop intragenic or gene combination pyramiding strategies to obtain more broad-spectrum and more durable resistance.

Keywords: plant innate immunity
New mechanisms of angiogenesis modulators in switching between white and brown adipose tissues (ANGIOFAT)

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: Sweden
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-03-01
End date: 2015-02-28
Duration (months): 60.0
Total project cost (EUR): 2411547.0
EU funding (EUR): 2411547.0
Participants: 1
Project status: CLOSED

Understanding the molecular mechanisms underlying adipose blood vessel growth or regression opens new fundamentally insight into novel therapeutic options for the treatment of obesity and its related metabolic diseases such as type 2 diabetes and cancer. Unlike any other tissues in the body, the adipose tissue constantly experiences expansion and shrinkage throughout the adult life. Adipocytes in the white adipose tissue have the ability to switch into metabolically highly active brown-like adipocytes. Brown adipose tissue (BAT) contains significantly higher numbers of microvessels than white adipose tissue (WAT) in order to adopt the high rates of metabolism. Thus, an angiogenic phenotype has to be switched on during the transition from WAT into BAT. We have found that acclimation of mice in cold could induce transition from inguinal and epidedymal WAT into BAT by upregulation of angiogenic factor expression and down-regulations of angiogenesis inhibitors (Xue et al, Cell Metabolism, 2009). The transition from WAT into BAT is dependent on vascular endothelial growth factor (VEGF) that primarily targets on vascular endothelial cells via a tissue hypoxia-independent mechanism. VEGF blockade significantly alters adipose tissue metabolism. In another genetic model, we show similar findings that angiogenesis is crucial to mediate the transition from WAT into BAT (Xue et al, PNAS, 2008). Here we propose that the vascular tone determines the metabolic switch between WAT and BAT. Characterization of these novel angiogenic pathways may reveal new mechanisms underlying development of obesity- and metabolism-related disease complications and may define novel therapeutic targets. Thus, the benefit of this research proposal is enormous and is aimed to treat the most common and highly risk human health conditions in the modern time.

Keywords: angiogenesis,obesity,diabetes,white adipose tissue,brown adipose tissue,antiobesity therapy,diabetic complications,metabolism
Gene transfer techniques in the treatment of cardiovascular diseases and malignant glioma (FUTUREGENES)

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: Finland
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-06-01
End date: 2015-05-31
Duration (months): 60.0
Total project cost (EUR): 2200000.0
EU funding (EUR): 2200000.0
Participants: 1
Project status: CLOSED

Background: Poor angiogenesis and collateral vessel formation lead to coronary heart disease, claudication, infarctions and amputations while malignant glioma is one of the most aggressive proangiogenic tumors leading to death in a few months. For these diseases either stimulation or blocking, respectively, of angiogenesis may provide novel treatment options. Advancing State-of-the-Art: Our hypothesis is that in ischemia it will be possible to support natural growth of blood vessels with Therapeutic angiogenesis and lymphangiogenesis by using local gene transfer of the new members of vascular endothelial growth factor (VEGF) family and their receptors. New co-receptors, designer mutants and PCR suffling products of VEGFs will be used. New vector technology will be used to achieve long-lasting effects of VEGFs. We aim to develop novel site-specifically integrating, targeted, regulated vectors to precisely express the new VEGFs, their soluble decoy receptors and single-chain therapeutic antibodies (scFv) for pro- and anti-angiogenic purposes. As novel approaches, we have developed metabolically biotinylated lenti- and adenoviruses suitable for targeting and Epigenetherapy where siRNA/miRNAs and short nuclear RNAs regulate endogenous gene expression at the VEGF promoter level via modification of histone code. scFv library for endothelial cells and lentivirus-siRNA library directed to all human and mouse kinases will be screened to identify new mediators of angiogenesis in order to develop next generation pro- and antiangiogenic therapies. Based on our strong track record in Clinical applications, the best new pro- and antiangiogenic approaches will be taken to phase I clinical studies in myocardial ischemia and malignant glioma. Significance: This work should lead to significant advances and new therapies for severe ischemia and malignant glioma. Epigenetherapy and new site-specifically integrating, regulated vectors should be widely applicable in medicine.
Limits to selection in biology and in evolutionary computation (SELECTIONINFORMATION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: Austria
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-07-01
End date: 2015-06-30
Duration (months): 60.0
Total project cost (EUR): 1975640.0
EU funding (EUR): 1975640.0
Participants: 1
Project status: CLOSED

Natural selection is the central concept in biology, and selection is widely used to solve hard computational problems. This proposal aims to deepen our understanding of selection, in both evolutionary biology and evolutionary computation, and to help bring these fields together. On the one hand, population genetics can show how to optimise genetic algorithms, and can inspire new algorithms. On the other, the central problem in evolutionary computation is to optimise the &quot;evolvability&quot; of the algorithms - an issue that has only recently become prominent in biology. Also, computer science may give biologists insight into how selection can concentrate information from the environment into complex organisms, and how organisms can develop under the guidance of their surprisingly small genomes. This project will focus on the factors that limit natural selection: lack of recombination, interaction between genes, and spatial subdivision. Novel techniques will be applied: multilocus algebra, branching processes, an analogy with statistical mechanics, and a new model for population structure. This analysis will be applied to biological and computational problems in parallel, focusing on how recombination aids selection; how epistasis may evolve to facilitate adaptation; and how selection acts in populations subject to frequent extinction and recolonisation. A new optimisation algorithm will be developed, which is amenable to mathematical analysis. Some components are straightforward, whilst others need new ideas, drawn from the interface between population genetics and computer science. Perhaps most challenging will be to understand how selection can so effectively gather information from the environment, so as to construct complex organisms.

Keywords: selection,information,entropy,recombination,population genetics,genetic algorithms,evolvability,population structure
Exploitation of Our Intestinal Microbiota (MICROBESINSIDE)

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,Finland
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-06-01
End date: 2015-05-31
Duration (months): 60.0
Total project cost (EUR): 2499000.0
EU funding (EUR): 2499000.0
Participants: 2
Project status: CLOSED

Our intestinal tract is colonized by a myriad of microbes that exceed our body cells in number and coding capacity and have important metabolic and signaling functions. Analysis of the diversity of these microbes inside revealed more than 1000 species, some of which have developed intimate interactions that are operating at the mucus interface separating the intestinal and microbial cells. Notably, we sustain and stimulate these interactions by feeding our microbes inside by the production of large amounts of mucus that equal the undigested components of our diet in caloric value. The understanding of the mucosal interactions is of great importance as they affect our immune system, signal to the brain-gut axis and provide a protective barrier against pathogens. Hence, this project aims to obtain fundamental understanding in the diversity and function of our microbes inside with a focus on mucus-binding bacteria that are either indigenous in the human intestine or ingested as part of our diet. The project will capitalize on (i) the recently developed high-throughput functional (meta)genomics approaches for human subjects, (ii) the genomic characterization of the mucus-degrading species Akkermansia muciniphila, an emerging biomarker for a healthy intestine, and (iii) the genome-driven discovery that the paradigm probiotic, Lactobacillus rhamnosus GG (LGG), contains cell-wall extended pili that strongly bind mucus and signal to human cells. A novel screening system will allow isolation of LGG derivatives with altered mucus-binding that will be instrumental in cause effect and other mechanistic studies. Moreover, the results will contribute to detailed insight in how our microbes inside develop mutualistic interactions, allowing for the design of new food-based approaches.

Keywords: intestinal microbiota,probiotic function,lactobacillus,metagenomics,industrial biosciences
A physical basis for wing morphogenesis and planar cell polarity (WING MORPHOGENESIS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: Germany
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-03-01
End date: 2015-05-31
Duration (months): 63.0
Total project cost (EUR): 1531200.0
EU funding (EUR): 1531200.0
Participants: 1
Project status: CLOSED

During development, physical forces are generated in precise patterns and produce elegant choreography of cell movements that determine tissue shape. The function of many tissues depends not only on their shape, but on the correct alignment of planar cell polarity within the tissue. Remarkably, recent evidence from my lab has suggested that physical forces not only shape the wing, but also align the planar polarity of its constituent cells with the proximal distal wing axis. The wing blade is remodeled at pupal stages by proximal-distal stretching caused by contraction of the wing hinge. Hinge contraction produces precise patterns of oriented cell rearrangements and cell divisions in the wing blade that lengthen it proximo-distally and refine its shape. The polarity of cell rearrangements also re-orients intracellularly polarized complexes of Planar Cell Polarity (PCP) proteins to face the distal side of the wing. This occurs because these complexes turn over very slowly, compared with the rate of cell rearrangement. We will investigate three problems defined by this work. First, how does polarized cell stretching cause epithelial remodeling? The pupal wing is the first in vivo example of this process in a genetically and physically accessible model. Second, what are the genetic, cellular, and physical mechanisms that specify the pattern of cellular flow occuring in the wing blade? Third, what signals orient PCP during early wing development? This previously undescribed early polarity is oriented roughly perpendicular to the final direction, is a critical starting point for the later development of proximal-distal polarity. This work will provide important insight into genetic, cellular and physical mechansisms that shape and polarize tissues.

Keywords: cell polarity