Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Sustainable competitiveness of SMEs in turbulent economic and social environments - a network approach (DYNAMIC SME)

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,Spain,Portugal
Call:  (FP7-PEOPLE-2010-IRSES, 2010)
Start date: 2011-06-01
End date: 2015-05-31
Duration (months): 48.0
Total project cost (EUR): 357000.0
EU funding (EUR): 357000.0
Participants: 3
Project status: CLOSED

The proposal aims at strengthening research partnerships through staff exchanges and networking activities between 2 European research organisations from Germany and Spain, and 2 research organisations from Argentina and Brazil. The scientific objective is to create a co-evolvement process towards a successful management model for SMEs that combines the European innovation and organizational learning model with Latin American survival strategies in turbulent economies (exemplified by Argentina and Brazil) based on learning networks and clusters. Both, in Europe and Latin America, SMEs are the most important sources of job creation and development in increasingly knowledge based economies. The economic environment in which SMEs operate, however, have differed significantly until recently. As the turbulence of the global economy is increasing European SMEs will have to learn to remain competitive in this new kind of economic environment. The answer lies in the development of “dynamic capabilities” of innovating, learning and knowledge management by SME networks. Following established theories and practices of organisational and social learning knowledge research activities are conceived as a joint learning and co-evolvement cycle in four phases Creating a joint vision,Learning from European approaches, Co-evolve SME model and practice in Argentina and Brazil,IHarvest and sustain. To achieve this objective a joint learning and co-evolvement process will be developed by four international research teams focusing on 1)Developing dynamic capabilities via SME networks and 2) via SME clusters , 3)Media + tools for developing dynamic capabilities, 4) monitoring dynamic capability development The proposed project will create 4 major impacts:1. A new understanding of sustainable SME management in turbulent economies. 2.Improved innovation and learning capabilities of SMEs. 3.A lasting community of scholars. 4. Wide dissemination and leverage to key actors

Keywords: business administration,small medium enterprise studies,knowledge managment,innovation management,intellectual capital reporting,action research
Cross-species characterisation of CD8alpha+ dendritic cells and their role in immune regulation (DCSUBSET)

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: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-09-01
End date: 2017-08-31
Duration (months): 72.0
Total project cost (EUR): 2499998.2
EU funding (EUR): 2499998.2
Participants: 2
Project status: CLOSED

Dendritic cells (DC) are a heterogeneous family of leucocytes with important functions in immunity. Little is known about the role of distinct DC subtypes in vivo. In the mouse, a subset known as CD8alpha+ DC has been argued to represent a discrete DC lineage with specialised properties. These include a superior capacity for presenting exogenous antigens to CD8+ and CD4+ T cells, which makes CD8alpha+ DC an attractive target in vaccination and tolerisation. However, it is unclear whether CD8alpha+ DC fulfill unique and non-redundant roles in the immune system. In addition, the reported restriction of CD8alpha+ DC to thymus and secondary lymphoid organs is hard to reconcile with their documented capacity to act as presenting cells for antigens outside those organs. Finally, CD8alpha+ DC have not been identified in humans, greatly restricting their use in immunotherapy. In this proposal, we exploit the recent finding that DNGR-1 (CLEC9A) acts as a new and specific marker for the CD8alpha+ lineage to address these issues. We will generate DNGR-1-Cre mice as a universal tool to manipulate gene expression in the subset. We will use such mice to render CD8alpha+ DC sensitive to toxic proteins that permit constitutive or transient ablation of the subset for functional studies. DNGR-1-Cre mice will further be used to express fluorescent proteins in CD8alpha+ DC, allowing tracing of the lineage in vivo, both in lymphoid and non-lymphoid organs. Finally, we will use the DNGR-1 marker to identify and characterise putative CD8alpha+ DC equivalents in humans. The results from this proposal will illuminate the function of CD8alpha+ DC across species and open the door for using this intriguing DC subset in immunotherapy of cancer, infectious and autoimmune diseases.

Keywords: dendritic cells antigen presentation
Human Genetics of Tuberculosis (GENTB)

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: France
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2047913.2
EU funding (EUR): 2047913.2
Participants: 1
Project status: CLOSED

Tuberculosis (TB) is not only an infectious disease, as only a small fraction of individuals infected with Mycobacterium tuberculosis (Mtb) develop disease. Over the last century, evidence has accumulated indicating that TB is also a genetic disease. However, the molecular basis of predisposition to TB remains elusive, and efforts to understand the pathogenesis of TB are of prime importance if we are to combat this major killer of mankind. The PI proposes an integrated and innovative research program aiming to identify the genetic variants controlling the critical steps of the process from exposure to Mtb to development of TB. In addition to investigating the two key clinical phenotypes - the development of disseminated TB in children and of pulmonary TB in adults - this program proposes to undertake the first comprehensive genetic dissection of resistance to Mtb infection. Making use of the latest conceptual and technical breakthroughs in human genetics, the strategy will combine Mendelian and complex genetics approaches, including genome-wide (GW) investigations (GW linkage and association studies, whole-exome sequencing). The strengths of this innovative, ground-breaking project lie in its bold hypothesis, the high quality of our clinical samples, and the extensive experience of our laboratory in human genetics of mycobacterial infections in terms of genetic epidemiology, molecular genetics, and immunology. The identification of the main variants controlling TB development will have major implications for TB control, both in the definition of new prevention strategies (design of vaccine research and clinical trials) and in the development of new treatments (aiming to restore deficient immune responses). These findings will also shift paradigms in both human genetics and infectious diseases, as - genetic TB - could provide proof-of-principle for a genetic theory of common infectious diseases.

Keywords: tuberculosis,linkage analysis,genome-wide association study,whole exome sequencing
Chemical Approaches to Restoring Vision (CARV)

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-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2484613.0
EU funding (EUR): 2484613.0
Participants: 1
Project status: CLOSED

Blindness affects millions of people worldwide and has devastating consequences for those affected. It is often caused by a loss of photoreceptors in the retina, whose residual cellular network remains largely unaffected. Various strategies have been chosen to restore vision, such as electrical stimulation with retinal implants. More recently, natural photoreceptor proteins and stem cells have been explored. We propose a radically different ¿photopharmacological¿ approach toward vision restoration that is based on synthetic photoswitches. These are combined in various ways with natural receptor proteins to create hybrid photoreceptors, which can then sensitize neurons toward light. In a way we are ¿teaching old receptors new tricks¿ and let them carry out functions that they have not evolved for in Nature. Our hybrid photoreceptors and photochromic drugs work well in experimental animals and have already been shown to influence their visual behavior. To make these molecules work in humans, we need to improve their photophysical properties and investigate their delivery, stability and pharmacology. This requires an extensive program in synthetic chemistry, which should be accompanied by effective and immediate neurobiological evaluation. Our very general approach to optically controlling neural activity can be applied to other functions and malfunctions of the nervous system, such as pain or epilepsy, but its greatest medical potential currently lies in the restoration of vision.

Keywords: retina,vision restoration,photopharmacology,receptor reengineering,ion channels,glutamate receptors,photophysics
NEW BIOLOGICAL FUNCTIONS AND THERAPEUTIC POTENTIAL OF VASCULAR ENDOTHELIAL GROWTH FACTORS (TX-FACTORS)

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-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2499884.0
EU funding (EUR): 2499884.0
Participants: 1
Project status: CLOSED

This application promises to provide new treatment options for cancer and cardiovascular diseases that are the leading causes of morbidity and mortality in the western world. Current cardiovascular and cancer therapies are often insufficient, unsuccessful or not suitable for all patients. Inhibition of angiogenesis is already used in the clinics, but with limited success. On the other hand, stimulation of the growth of blood vessels, angiogenesis, and of arteriogenesis, the growth of (collateral) arteries, has been unsuccessfully tried for the treatment of tissue ischemia. The aim of this research plan is to reveal new disease-related functions of endothelial growth factors and their signal transduction in cancer and cardiovascular disease and to establish preclinical models of effective therapy based on new knowledge of the biology of vascular endothelial growth factors (VEGFs), angiopoietins (Ang), angiogenesis and lymphangiogenesis. We will embark on new studies based on our novel discoveries on the crosstalk between endothelial growth factor pathways in tumor angiogenesis, the involvement of lymphatic vessels in the development of obesity and associated inflammation, and on the striking effects of VEGF-B on cardiac muscle and vessels. We will develop molecular genetic and iPS cell derived models, and use functional genomics, proteomics and metabolomics, viral gene delivery and blocking reagents from human antibody libraries for our studies that should be of high priority in basic science and medicine. My laboratory is uniquely suited and networked for new discoveries to advance therapies for both cancer and cardiovascular diseases. Some of our work has already been translated to clinical development and we aim to provide additional drug candidates in this project.

Keywords: angiogenesis
Neurogenesis in the adult human brain (NEURAL RENEWAL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Sweden
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2491235.0
EU funding (EUR): 2491235.0
Participants: 1
Project status: CLOSED

One of the characteristics of the central nervous system is its plasticity, with for example a remarkable capacity to store new information. It was for long time thought that there was very little plasticity in terms of exchanging cells and that we essentially were limited to the neurons we were born with. It is now well established that new neurons are added to certain regions of the adult brain in most mammals, although it has been very difficult to study in humans. The proposed project aims to unveil the cell lineage producing new neurons in the adult human brain and to assess the extent of neurogenesis and how it may change in for example aging and neurological and psychiatric diseases. We propose to take advantage of the rapid development of sequencing technology to assess the origin and lineage of new cells in the human brain by phylogenetic fate mapping. This will be combined with the analysis of the turnover of neurons in the adult human brain by a retrospective birth dating methodology which we recently have developed based on the integration of nuclear bomb test derived 14C. This is a cross-disciplinary project that bridges from basic cell and molecular biology, latest generation DNA sequencing technology via clinical medicine and mathematical modeling to nuclear physics. A possible role for alterations in adult neurogenesis in the etiology of both depression and schizophrenia has recently received much interest. However, the link between neurogenesis and psychiatric diseases is based on a series of indirect indications, mainly in experimental animals. It is pivotal to gain direct information on the relationship between neurogenesis and psychiatric and neurological diseases in humans.

Keywords: accelerator mass spectrometry,sequencing,depression
Image Guided Local Drug Delivery from Nanocarriers using Focused Ultrasound (SOUND PHARMA)

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: Netherlands
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-12-01
End date: 2016-11-30
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

The principal objective of the Sound Pharma project is to increase the therapeutic index of potent, often toxic treatments through personalized image-guided treatment, which ultimately decreases adverse effects of drugs by better controlling the pharmacokinetics (PK) and pharmacodynamics (PD) of therapy. For local disease, exogenous energy will be used to to release drugs entrapped within nanoparticles circulating through the tumor. This will be achieved via a combination of Focused Ultrasound, and drug nanocarriers that are sensitive to bio-effects of ultrasound. The drug ¿magic bullet¿ is at the heart of Pharma¿s business model. However, targeted drug delivery is increasingly being recognized as a key limiting factor of drug efficacy. Nanotechnologies are providing new formulations as well as novel methods for targeting. The combination of nanotechnologies and external triggering will provide novel technologies to achieve spatio-temporal control of drug delivery. The effect of ultrasound in tissue allows the local deposition of drugs from nanocarriers circulating in the blood, and/or their local activation. This is the case when using nanocarriers sensitive to mechanical forces and/or to small temperature elevations. Extravasation and membrane permeability are also enhanced by ultrasound. This new field of Image Guided Drug Delivery opens up opportunities for Pharma to expand applications for their existing small drugs (e.g. doxorubicin, cisplatin, irinitecan) in cancer by altered pharmacokinetics. This project intends to develop new focused ultrasound methods for drug delivery, based on local control of temperature and pressure, and by monitoring and validating intracellular uptake in real time using optical and MRI methods. The developed FUS methods will be applied to treatment of liver cancer using nanocarriers containing well known chemotherapeutica, via animal models, as well as in the clinic.

Keywords: drug nanocarriers,focused ultrasound,magnetic resonance imaging,ultrasound imaging,optical imaging,targeted drug delivery
Modeling lymphoma pathogenesis in mice - from basic mechanisms to pre-clinical models (LYMPHOMA)

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: 2011-07-01
End date: 2016-12-31
Duration (months): 66.0
Total project cost (EUR): 2487787.0
EU funding (EUR): 2487787.0
Participants: 1
Project status: CLOSED

Human B cell lymphomas including multiple myeloma and Hodgkin¿s disease are frequent malignancies and a major clinical problem. Their high incidence is due to special features of normal B cell development that promote chromosomal translocations and other genetic alterations. Another contributing factor is Epstein-Barr-Virus (EBV), a B cell-transforming virus endemic in humans. EBV-infected cells are usually eliminated by the immune system, but in immunosuppressed (post-transplant or AIDS) patients, EBV infection spreads and drives lymphomagenesis. We have generated a novel genetic tool that allows us to introduce combinations of loss- and gain-of-function mutations specifically into B cells in the mouse, to analyze the cooperation of oncogenic factors thought to contribute to B lymphomagenesis in humans. The unique feature of this method is that only a small fraction of cells is mutated (mimicking the sporadic nature of somatic cancerogenesis) and that cells having acquired either single or combined mutations can be observed side-by-side. Using a large set of mutant alleles, we will test whether the interplay of certain combinations of survival, proliferation and differentiation signals determines the development of different classes of human B cell malignancies. A special focus is on Hodgkin¿s disease, where EBV infection and genetic reprogramming play a critical role. We will also investigate the mechanism of immune surveillance of EBV-infected B cells and EBV-driven B cell lymphomas. Ultimately we hope to elucidate key pathways of lymphoma pathogenesis, identify novel contributing mutations, and generate preclinical mouse models to assess therapeutic strategies and mechanisms of tumor immune surveillance.

Keywords: b-cell lymphoma,hodgkin's disease,ebv,immune surveillance,mouse models,conditional gene targeting
Gene Therapy for Inherited Skin Adhesion Disorders (GT-SKIN)

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: France
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-12-01
End date: 2017-05-31
Duration (months): 66.0
Total project cost (EUR): 2210000.0
EU funding (EUR): 2210000.0
Participants: 1
Project status: CLOSED

Epidermolysis bullosa (EB) is a family of severe skin adhesion defects characterized by disfiguring blistering, infections, visual impairment, and a high risk of cancer. We showed through pre-clinical and clinical investigation that transplantation of genetically corrected epithelia leads to long-term functional correction of EB. The current vectors, however, integrate in an uncontrolled fashion in the human genome, a cause of genotoxicity and potentially severe adverse events. The objective of this project is the development and pre-clinical evaluation of new gene targeting and gene correction technology, aimed at integrating therapeutic transgenes at specific loci or at correcting genetic defects by homologous recombination. Epidermal stem cells (EpSCs) and EB are ideal targets for the design and development of such technology, which is expected to have an impact on gene therapy of many other genetic diseases. We will design and test novel viral vectors for homologous recombination based on site-specific integrases and Zn-finger nucleases, and non-viral vectors for integrating large genes and complex regulatory sequences based on vertebrate transposons. All vectors will be tested in repopulating human EpSCs in vitro and in vivo, in a pre-clinical model of xenotransplantation of human skin on immunodeficient mice. A parallel, basic research program will aim at applying existing and novel genomic approaches to the definition of transcription factors, regulatory regions and gene expression programs involved in self renewal, commitment and differentiation of EpSCs. The anticipated output of the project is the development of next-generation technology for gene transfer, and the establishment of a knowledge base for a better utilization of EpSCs in gene therapy.

Keywords: gene transfer,homologous recombination,gene targeting,gene regulation,transcription factors
Disseminating tumor cells as novel biomarkers: Dissecting the metastatic cascade in cancer patients (DISSECT)

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-2010-AdG_20100317, 2010)
Start date: 2011-08-01
End date: 2016-07-31
Duration (months): 60.0
Total project cost (EUR): 2499000.0
EU funding (EUR): 2499000.0
Participants: 1
Project status: CLOSED

Breast, prostate, lung and colorectal cancer as solid tumours derived from epithelial tissues are responsible for 90% of all new cancers in Europe. Present tumour staging is mainly based on local tumour extension, metastatic lymph node involvement and evidence of overt distant metastasis obtained by imaging technologies. However, these staging procedures are not sensitive enough to detect early tumour cell dissemination as a key event in tumour progression. Our team has therefore focused on the development of ultrasensitive assays that allow the specific detection and molecular characterization of single tumour cells in bone marrow (DTC) and blood (CTC) of cancer patients. These methods allow the direct assessment of disseminating tumour cells including the detection of therapeutic targets and mechanisms of resistance in patients undergoing therapy. Based on our established network of clinical collaborations, the DISSECT project will detect and characterize DTC/CTC in patients with the four most frequent tumour entities in the EU by high resolution methods. We will investigate representative clinical studies for current interventions that may have an impact on tumour cell dissemination, including diagnostic biopsies, surgical resection of the primary tumour, radiotherapy, chemotherapy and in particular targeted therapies. The technologies for DTC/CTC analyses previously developed by our team will be complemented by cutting-edge technologies and adapted to the analysis to decisive molecular processes underlying the particular intervention. The results obtained in the DISSECT project will provide unique insights into the biology of tumour cell spread in humans and these insights might lead to improved concepts in the clinical management of cancer patients.

Keywords: cancer (micro-)metastasis,circulating tumor cells,solid tumors,cancer therapy