Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Feeling with Light – Development of a multimodal optofluidic platform for high-content blood cell analysis (LIGHTTOUCH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1385683.0
EU funding (EUR): 1385683.0
Participants: 1
Project status: CLOSED

The reliable characterization of heterogeneous cell populations is a central prerequisite in many areas of medicine, biology, and biotechnology. Conventional techniques used for this purpose are either high-throughput, such as fluorescence-activated cell sorting (FACS), but limited to a small number of parameters or high-content, such as slide-based imaging approaches, which require surface attachment and preclude cell sorting. It is the overall objective of this proposal to develop a multimodal, microfluidic, laser trap-assisted cell screening platform technology – µFLAX – for the contact-free manipulation and high-content screening of suspended cells with high-throughput. Our approach is especially designed for blood cells, which will be serially trapped from microfluidic flow with a dual-beam trap. In addition to the extraction of molecular information (similar to FACS), we also incorporate mechanical phenotyping as a powerful new functional cell marker. In addition to looking, we can feel for functional changes using optically induced forces. This will be further augmented by structural analysis using digital holographic microscopy, cell size analysis using an optical cell rotator, and biological stimulation by microfluidic delivery of biochemical agents. This combination will offer much higher sensitivity and specificity in determining functional states compared to currently available techniques. And since the cells are suspended they can be sorted and analyzed further, which will aid potential molecular target identification. Once developed, we will demonstrate the applicability of µFLAX for the investigation and diagnosis of inflammation and infection. Based on our track record in pioneering innovative physical solutions to biomedical problems we anticipate that through this project we will provide novel insight into system biological aspects of these disorders on the single-cell level, as well as novel diagnostic and therapeutic options.

Keywords: laser trapping and micromanipulation,microfluidics,quantitative phase microscopy,cytoskeleton,cell mechanics,infection,inflammation
Minimalist multipurpose ATP-binding cassette transporters (ABCTRANSPORT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Netherlands
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-12-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Many Gram-positive (pathogenic) bacteria are dependent on the uptake of vitamins from the environment or from the infected host. We have recently discovered the long-elusive family of membrane protein complexes catalyzing such transport. The vitamin transporters have an unprecedented modular architecture consisting of a single multipurpose energizing module (the Energy Coupling Factor, ECF) and multiple exchangeable membrane proteins responsible for substrate recognition (S-components). The S-components have characteristics of ion-gradient driven transporters (secondary active transporters), whereas the energizing modules are related to ATP-binding cassette (ABC) transporters (primary active transporters). The aim of the proposal is threefold: First, we will address the question how properties of primary and secondary transporters are combined in ECF transporters to obtain a novel transport mechanism. Second, we will study the fundamental and unresolved question how protein-protein recognition takes place in the hydrophobic environment of the lipid bilayer. The modular nature of the ECF proteins offers a natural system to study the driving forces used for membrane protein interaction. Third, we will assess whether the ECF transport systems could become targets for antibacterial drugs. ECF transporters are found exclusively in prokaryotes, and their activity is often essential for viability of Gram-positive pathogens. Thus they could turn out to be an Achilles’ heel for the organisms. Structural and mechanistic studies (X-ray crystallography, microscopy, spectroscopy and biochemistry) will reveal how the different transport modes are combined in a single protein complex, how transport is energized and catalyzed, and how protein-protein recognition takes place. Microbiological screens will be developed to search for compounds that inhibit prokaryote-specific steps of the mechanism of ECF transporters.

Keywords: membrane protein membrane transport vitamin uptake
Targeting Src-family tyrosine kinases in chronic autoimmune and inflammatory diseases (TARKINAID)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Hungary,Germany,Italy,France,Germany,Brazil,France,Greece
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2012-01-01
End date: 2015-12-31
Duration (months): 48.0
Total project cost (EUR): 3912000.0
EU funding (EUR): 2999860.0
Participants: 11
Project status: CLOSED

The project aims to develop novel inhibitors of chronic autoimmune and inflammatory diseases by targeting members of the Src tyrosine kinase family. Src-family kinases have recently emerged as major therapeutic targets in malignant diseases but their suitability as potential targets of inflammatory diseases has not yet recieved widespread acceptance. On the other hand, members of the applicant consortium have recently obtained genetic evidence showing that myeloid Src-family kinases (Hck, Fgr and Lyn) are indispensable for murine models of autoimmune inflammatory diseases such as rheumatoid arthritis or blistering skin diseases. They also developed a number of novel Src-family kinase inhibitors that also block inflammation-related in vitro leukocyte functions. The applicants will test and further develop novel Src-family kinase inhibitors as anti-inflammatory compounds, using several in vitro and in vivo inflammation assays to optimize the structure of the selected molecules. They will also test whether Src-family inhibitors already in clinical use in oncology patients also inhibit inflammatory processes. Finally, they will use Src-family kinase-deficient mice in several inflammation models to test the role of those kinases in more detail and to provide further reference information for the consortium's preclinical drug development activity. The selected inhibitors and mutant mice will be pre-screened using various inflammation-related in vitro leukocyte functions and short-term in vivo inflammation models, and then analyzed in detail using a number of in vivo mouse models of chronic autoimmune and inflammatory diseases. The project is expected to result in development of novel preclinical drug candidates against chronic autoimmune and inflammatory disease with novel mechanism of action, as well as novel knowledge on the role of Src-family kinases in inflammatory diseases. The project will be performed in close cooperation between European and Brazilian scientists.

Keywords: chronic autoimmune and inflammatory diseases,kinase inhibitors,novel therapeutic targets,in vivo disease models,src-family kinases
Protease Systems Biology in Tumorigenesis and Neurodegeneration (PROTEASYS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1499760.0
EU funding (EUR): 1499760.0
Participants: 1
Project status: CLOSED

Proteolysis affects every protein through limited processing or degradation. Unlike other post−translational modifications, proteolysis is irreversible and occurs intra− and extracellularly. The large number of genetically encoded proteases in man (> 560) illustrates the importance of proteolysis. However, the in vivo substrate profiles of most proteases have remained elusive; presenting a major hurdle to understanding protease function in health and disease. System−wide identification of protease substrates is now enabled by novel proteomic strategies for the quantitative determination of neo N− and C−termini. In this project, proteolytic events and cleavage products are identified and validated in cellular model systems in order to understand how proteolysis contributes to tumor aggressiveness and neurodegeneration. In the area of tumor biology, the paracrine loop between cancer and stroma cells is dissected. Both cell types secrete cytokines and cytokine−modifying proteases; thereby potentiating tumor proliferation and invasiveness. Identification of key cleavage events and key proteases in tumor−stroma interaction unravels the role of proteolysis in cellular communication. In addition, the substrate profile of the stroma−specific, cell−surface protease “Fibroblast activation protein” is determined. In the area of neurodegeneration, this project identifies and validates substrates of the orphan, neuroprotective protease DJ−1. Mutants of DJ−1 are associated with early−onset Parkinsonism. In addition a novel dual−label approach for the monitoring protein−specific degradation rates on a proteome−wide scale is established. This unique strategy examines the relation between a–synuclein aggregation (a hallmark of Parkinson’s disease) and impaired proteome turnover. The combination of novel proteomic techniques with state−of−the−art cell biological approaches is uniquely suited to determine how proteases control cellular fate in tumorigenesis and neurodegeneration.

Keywords: proteolysis,degradomics
Decoding the environmental adaptation of plant stem cell control (STEMCELLADAPT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1494000.0
EU funding (EUR): 1494000.0
Participants: 1
Project status: CLOSED

As sessile organisms, plants are exposed to extreme variations in the environment over the course of their lives. Since plants initiate new organs continuously, they have to modulate the underlying developmental program to cope with this challenge. At the heart of this extraordinary developmental plasticity are pluripotent stem cells, which are maintained during the entire life-cycle and that are embedded within dynamic stem cell niches. Consequently, stem cell systems in plants respond strongly to variations in environmental conditions, in order to synchronize stem cell behavior with the overall growth status of the plant. In the proposed project we will study cell behavior in the apical stem cell niche and define the epigenetic and transcriptional states of stem cells and niche cells to elucidate how these cells are reprogrammed by environmental influences using advanced live imaging and cell type specific genomics, respectively. In addition, we will use these technologies to study how natural genetic variation impacts on stem cell behavior and the molecular signatures, which define these cells. Using comparative analysis we will identify loci that are responsive to specific environmental changes and study them functionally by advanced cell type specific genetics. To elucidate how environmental stimuli are sensed by the stem cell regulatory system, we will systematically test known regulators of light, temperature and metabolic signaling for their role in this process, both by traditional, as well as by advanced cell-type specific genetics. Together, these datasets will give an unprecedented insight into how plant stem cells perceive environmental signals and how their transcriptional and epigenetic programs respond under changing environments. In addition, our experiments will reveal whether the mechanisms of short-term environmental acclimatization of the regulatory system converge with the long-term evolutionary adaptation of organisms to their environment.
INTEGRATION OF GENOMICS AND CARDIOMETABOLIC PLASMA BIOMARKERS FOR IMPROVED PREDICTION AND PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE (CARDIOPREVENT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Sweden,France
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-12-01
End date: 2016-11-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 2
Project status: CLOSED

By taking advantage of great experience in genetic and cardiovascular epidemiology and some of the largest cohorts in the world including 60 000 unique individuals, the applicant aims at (1) improving CVD risk prediction and (2) identifying mechanisms causally related to CVD development in order to provide novel targets for drug discovery and targeted life style interventions for use in primary prevention. In SUBPROJECT 1 we aim at identifying disease causing alleles of loci implicated in CVD by Genome Wide Association Studies (GWAS) and to identify rare alleles with large impact on human CVD. We thus perform whole exome and targeted sequencing in early CVD cases and healthy controls and evaluate all identified variants by relating them to incident CVD in 60.000 individuals. Further, we will create a score of all validated CVD gene variants and test whether such a score improves clinical risk assessment over and above traditional risk factors. In SUBPROJECT 2 we test whether the plasma metabolome- a phenotype representing the product of dietary intake and inherent (e.g. genetic) metabolism- differs between incident CVD cases and controls and between individuals with high and low CVD genetic risk. We further test whether a life style intervention differentially alters the plasma metabolome between individuals with high and low CVD genetic risk. Finally, we will elucidate the mechanisms underlying CVD genetic associations by testing whether myocardial expression of such genes are affected by experimental myocardial infarction (MI) and whether heart function, MI size and the plasma metabolome are affected by adenoviral myocardial CVD gene transfer in rats. In SUBPROJECT 3 we test whether glucose metabolism and CVD risk factors can be ameliorated by suppressing vasopressin (VP) by increased water intake in humans. Finally, we test which of the 3 VP receptors is responsible for adverse glucometabolic VP effects in rats by specific VP receptor pharmacological studies.

Keywords: cardiovascular prediction primary prevention of cardiovascular disease
POLARITY AND SUBCELLULAR DYNAMICS IN PLANTS (PSDP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Austria,Belgium
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 2
Project status: CLOSED

Plant life strategy is marked by acquisition of highly flexible development that adapts plants’ phenotype to the environment. Various environmental signals are integrated into the endogenous signalling networks involving the versatile phytohormone auxin. The intercellular auxin transport mediates a large variety of adaptive plant growth responses. Subcellular polar distribution of PIN auxin transporters determines directionality of auxin flow and thus have potential to integrate internal and external signals via the redirection of auxin fluxes and translate them into modulation of development. Auxin transport thus represents a unique model for studying the functional link between basic cellular processes, such as vesicle trafficking and cell polarity, and their developmental outcome at the level of the multicellular organism. We will employ approaches of cell biology, molecular genetics and chemical genomics in Arabidopsis thaliana to identify the cellular and molecular mechanisms regulating the directional throughput of auxin flow a integration of environmental signals into subcellular dynamics of PIN auxin transporters as well as endogenous feed-back regulations of this mechanism. In our proposal, we will focus on four main research directions. 1. Novel regulators of cell polarity identified by chemical genomics 2. Cellular mechanisms of cell polarity maintenance 3. Integration of signals into subcellular dynamics of auxin transport 4. Mathematical modelling of regulatory circuits for adaptive development The results will demonstrate the viability of genetics approaches for addressing cell biological questions in plants, open new horizons in plant cell biology and plant hormone fields and inspire researchers also in non-plant fields. The expected output has clear application potential for targeted modulation of plant development. The project will further strengthen our position of world-leading laboratory in plant hormone and plant cell biology fields.
International Forum for Aviation Research Support Action (IFARS)

Framework: FP7 — Cooperation
Programme: Transport (including Aeronautics)
Destination: Aeronautics and air transport
Action type: Coordination and support actions
Countries involved: Germany
Call:  (FP7-AAT-2011-RTD-1, 2011)
Start date: 2011-06-15
End date: 2014-12-14
Duration (months): 42.0
Total project cost (EUR): 231316.0
EU funding (EUR): 200000.0
Participants: 1
Project status: CLOSED

Climate change is one global topic which is currently world-wide discussed by politicians and scientists. The Forth Assessment Report of the International Panel on Climate Change (IPCC) has stirred an intensive public debate on future aeronautical research challenges and policies. This report identifies aviation to contribute 2–3 percent of today’s total global anthropogenic CO2 emissions. This prompted the International Air Transport Association (IATA) to set the long term challenge of Zero Emission Aviation by 2050 and emphasised the importance of addressing these challenges on a global level. The answers and solutions to these demands are expected to be given by research. Except networks on continent level (e.g. EREA in Europe), the worldwide aerospace research organisations are currently not coordinated and do not have a representative who can react to the political questions and demands. The German Aerospace Center (DLR) took this need as opportunity to organise 2008 and 2010 a Summit and invited key leaders of international aeronautical research to address the question of the Air Transport of the Future in the context of climate change. In 2008, the participants discussed possibilities and strategies. In 2010 the participants founded the International Forum for Aviation Research (IFAR) which aims to find potential solutions for ecologically and economically efficient flights. IFAR will develop a Road Map addressing the most important questions regarding the aviation challenges; the global air transport system's efficiency, atmospheric impact but also other topics as safety, noise and new technologies. Thus the strategic goal of IFAR is to generate and to collaborate in the aviation research challenges and technology avenues worldwide. The proposed EU project IFARs is a Support Action which aims to support IFAR within the next 3 years.

Keywords: aviation,international forum,climate change,noise,safety,security
Sequence based strategies to identify genetic variation associated with mental retardation and schizophrenia (GENOVAR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: Sweden
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-08-01
End date: 2017-07-31
Duration (months): 60.0
Total project cost (EUR): 1496574.0
EU funding (EUR): 1496574.0
Participants: 1
Project status: CLOSED

Mental retardation (MR) and schizophrenia (SCZ) are disorders of the brain that affect 2-3% and 1% of the population, respectively. Both disorders are considered to be highly heritable, but exhibit heterogeneous genetic etiology. Recent genetic studies have led to discoveries that the same variants that can give rise to different neuropsychiatric disorders, including MR and SCZ. In this proposal, sequencing will be used to identify novel genes involved in MR and SCZ, and to explore the potential overlap between these disorders. The specific goals of the research plan include: 1. Genetic characterization of patients from large pedigrees with SCZ and MR. Five pedigrees have been collected in which multiple individuals are affected by SCZ or MR. The pedigrees vary in size, with the largest spanning 12 generations including 3,400 individuals. Exome and whole genome sequencing will be performed to identify the genetic variants associated with disease. Candidate genes identified will be screened in large independent cohorts of MR and SCZ patients. In addition, RNA sequencing will be performed on cell lines established for patients and controls from two of the pedigrees. 2. Screening of trios to identify novel genes causing MR Mental retardation (MR) patients are typically referred for array-based analysis. With current genetic screening using microarray, a clinically significant rearrangement is identified in 15-20% of patients. I propose use high throughput sequencing to screen MR patients and their parents with the goal of identifying new MR genes and to investigate to what extent the diagnostic yield can be increased. By combining sequencing, bioinformatics and carefully selected clinical material, the work presented in this proposal will lead to an increased understanding of disease mechanisms and enable the development of novel targets and strategies for molecular diagnostic screening.

Keywords: exome sequencing,mental retardation,schizophrenia,transcriptome sequencing