Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Neuron-Glia Interactions in Nerve Development and Disease (NGIDD)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,Israel,Italy,United Kingdom,Germany,United Kingdom,Germany
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-04-01
End date: 2012-03-31
Duration (months): 48.0
Total project cost (EUR): 3887956.0
EU funding (EUR): 3000000.0
Participants: 8
Project status: CLOSED

The characteristic appearance of white matter in the nervous system results from a remarkable cellular structure called myelin. This membraneous sheath is wrapped around axons by dedicated glial cells, thereby allowing the rapid propagation of impulses along the axons. The importance of the myelin sheath is underscored by the many neurological diseases that are caused by loss or destabilization of the myelin sheath, such as multiple sclerosis, leukodystrophies and peripheral neuropathies. The formation and maintenance of myelin by Schwann cells and oligodendrocytes results from close interactions between the neuron and glia cell. However, despite the vast importance of myelin to the normal physiological function of the nervous system, the molecular mechanisms underlying axon-glial communication in health and disease still remains largely unknown. In this collaborative project we aim to unravel these molecular mechanisms, discover novel molecules involved in neuron-glia communication and identify and test new targets for pharmaceutical intervention to aid the regenerative capacity of the nervous system.

Keywords: myelin,signaling,cell-adhesion,neuron,glia
Genomic Instability in Cancer and Precancer (GENICA)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Switzerland,Finland,Denmark,Spain,Italy,Greece,United Kingdom,Denmark,France
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-01-01
End date: 2010-12-31
Duration (months): 36.0
Total project cost (EUR): 4835047.0
EU funding (EUR): 2994979.0
Participants: 11
Project status: CLOSED

Genomic instability is a characteristic of practically all human cancers. Recent results generated by members of this Consortium suggest that signs of genomic instability are evident from the very beginning of human cancer development, even in precancerous lesions. In these early lesions, the genomic instability affects primarily specific genomic loci, called common fragile sites. Because common fragile sites are very sensitive to perturbations in DNA replication, we proposed that cancer development from its very beginning is associated with DNA replication stress. A separate set of observations focused on telomeres and showed that short telomeres mimick DNA ends, activate the DNA damage checkpoint and promote genomic instability and cancer development. We propose here to study the role of DNA replication stress and short telomeres on driving genomic instability particularly in human precancerous lesions. Our studies will investigate the most common forms of cancer in the EU and will benefit from access to some of the largest databases of cancerous and precancerous lesions in Europe. Genomic instability will be explored using high resolution genomic arrays and the data will be correlated to clinical information on tumor progression. Further, analysis of proteins and genes involved in the cellular response to DNA replication stress and short telomeres will be explored using high throughput and targeted approaches and will be used to identify novel targets for cancer therapy.

Keywords: pre-cancerous lesions,dna replication stress,genomic instability,cell cycle checkpoints
HGF/SF and MET in metastasis (SFMET)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: United Kingdom,Italy,Germany,Italy
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-04-01
End date: 2011-09-30
Duration (months): 42.0
Total project cost (EUR): 4141339.4
EU funding (EUR): 2927008.0
Participants: 4
Project status: CLOSED

The growth and motility factor HGF/SF and its receptor MET define a paracrine signalling system which controls the migration of several cell lineages in embryogenesis and tissue repair. In a large number of human tumours, cancer cells hijack HGF/SF and MET signalling in order to invade adjacent tissue and initiate metastasis. The evidence for this is strong, broad and consistent and highlights HGF/SF and MET as key effectors of tumour invasion and primary targets for therapy. This proposal has two objectives. The first is to understand the mechanism by which HGF/SF and MET cause tumour invasion and, specifically: - how local hypoxia induces MET over-expression in tumour cells and how the MET - WNT and the MET - chemokine pathways cooperate in metastasis. The second aim is to develop MET therapeutics. These will include: (i) a protein antagonist built from a fragment of the ligand known as NK1, (ii) low molecular weight MET antagonists and, (iii) inhibitors of SHP-2, a critical effector of MET signalling. NK1 will be engineered as a receptor antagonist on the strength of available crystal structures. Low molecular weight MET antagonists and SHP-2 inhibitors will be developed on the strength of: - the availability of recombinant forms of the target proteins, - suitable screening methodologies and, - the results of initial screens that have provided robust proof of principle for both approaches. The proposal thus builds on strong progress in participating laboratories on the structure and function of HGF/SF and MET and fulfils the three key criteria described in the call for proposal ‘Understanding and fighting metastasis’, namely: (i) it addresses a key mechanism of dissemination of human tumours, (ii) contributes to understanding the interplay between the tumour microenvironment (the source of HGF/SF) and tumour cells (the cells that express the MET receptor) and, (iii) has considerable prospects of delivering novel therapeutics for metastatic cancer

Keywords: hgf/sf,met,shp-2,tumour invasion,metastasis,hypoxia,nmr,x-ray crystallography,protein engineering,high-throughput screening,fragment-based drug discovery.
Developmental Molecular Pathways in Drosophila as a Model for Human Cancer (CANCERPATHWAYS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,Austria,United Kingdom,United Kingdom,Spain,Germany,Hungary
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-05-01
End date: 2011-10-31
Duration (months): 42.0
Total project cost (EUR): 4438623.4
EU funding (EUR): 2995295.0
Participants: 8
Project status: CLOSED

Cancer is often characterized as a disease of signal transduction pathways, since it is frequently associated with inappropriate activation of such pathways. Indeed, new therapeutic approaches in cancer therapy, such as Herceptin, frequently target signaling pathway components to revert their pathophysiological aberrations. Most oncogenic pathways have been highly conserved throughout evolution with Drosophila representing a particularly powerful genetic model for the analysis of such signaling cascades. These cancer pathways include Wnt, Notch, Hippo and JAK/STAT pathways. The analysis of signaling pathways in Drosophila is facilitated by the availability of a broad range of genetic tools, a completely sequenced genome and the availability of genome-wide collections of RNAi reagents. Within this project, we will establish high-throughput cell-based assays for regulators of the major developmental oncogenic signaling pathways. Cell-based assays for signaling pathways will be screened using genome-wide RNAi and small molecule compound libraries to identify new components, regulators and targets. Suppressor/enhancer screens in cultured cells will be used to identify small molecular compounds that interfere with the activity of specific signaling pathways and in vivo models of signaling pathways will be established to test the activity of drugs using developmental and tumorogenic phenotypes. By integrating and standardizing data from most important cancer relevant signaling pathways and combining them with powerful bioinformatics tools, we expect to get highly validated information on possible drug targets and lead substances. The collaborative project integrates recent technological advances, such as genome-wide RNAi libraries for cell-based and in vivo assay models that were developed by the participants, as well as computational approaches and databases to integrate and disseminate the information obtained during the project.

Keywords: signaling pathways,drosophila,rnai,drug screening,high-throughut assays
Oncolytic adenoviruses expressing monoclonal antibody trastuzumab for treatment of Her-2+ cancer (TRASTUZUCRAD)

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: Finland
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2014-08-31
Duration (months): 72.0
Total project cost (EUR): 1622360.0
EU funding (EUR): 1622360.0
Participants: 1
Project status: CLOSED

Metastatic breast, ovarian, gastric and esophageal cancer are currently incurable and therefore require new and innovative treatment approaches. The objective of this project is to construct oncolytic adenoviruses that code for trastuzumab (HerceptinR), a monoclonal antibody against tumor associated receptor Her2. Intravenous trastuzumab is already widely used for treatment of Her2+ breast cancer, and is being actively studied for other tumor types that frequently feature Her2 amplification, including ovarian, gastric and esophageal cancer. We hypothesize that expression of the antibody from a virus will result in production of high, sustained concentrations of functional trastuzumab in situ. In comparison to conventional intravenous delivery, this might results in enhanced anti-tumor activity but reduced systemic exposure and side-effects. Further, a single injection of the virus might result in prolonged production of trastuzumab which might be cost-effective as intravenous trastuzumab is expensive. The viruses will be targeted for effective delivery to tumor cells through viral capsid modifications, and oncolytic cell killing will proceed only in p16/Rb pathway mutant tumor cells. Trastuzumab production will be coupled to virus replication. Further, trastuzumab is secreted into the surrounding tumor tissue for an effective “bystander effect”, ie. killing of neighboring tumor cells. In summary, we hypothesize that this approach will result in tumor cell killing through viral oncolysis, the anti-tumor activity of trastuzumab, and the potential synergy between the approaches. Further, high local concentrations might result in anti-tumor efficacy superior to efficacy seen with intravenous trastuzumab. These developments might eventually result in increased treatment options for patients with currently incurable Her2+ cancers.

Keywords: oncolytic viruses,adenovirus,cancer gene therapy,monoclonal antibodies,trastuzumab
Architectural design In Dialogue with dis-Ability Theoretical and methodological exploration of a multi-sensorial design approach in architecture (AIDA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Individuals, institutions and markets
Countries involved: Belgium
Call:  (ERC-2007-StG, 2007)
Start date: 2008-05-01
End date: 2013-10-31
Duration (months): 66.0
Total project cost (EUR): 1195385.0
EU funding (EUR): 1195385.0
Participants: 1
Project status: CLOSED

This research project is based on the notion that, because of their specific interaction with space, people with particular dis-abilities are able to appreciate spatial qualities or detect misfits in the environment that most architects—or other designers—are not even aware of. This notion holds for sensory dis-abilities such as blindness or visual impairment, but also for mental dis-abilities like autism or Alzheimer’s dementia. The experiences and subsequent insights of these dis-abled people, so it is argued, represent a considerable knowledge resource that would complement and enrich the professional expertise of architects and designers in general. This argument forms the basis for a methodological and theoretical exploration of a multi-sensorial design approach in architecture. On the one hand, a series of retrospective case studies will be conducted to identify and describe the motives and elements that trigger or stimulate architects’ attention for the multi-sensorial spatial experiences of people with dis-abilities when designing spaces. On the other hand, the research project will investigate experimentally in real time to what extent design processes and products in architecture can be enriched by establishing a dialogue between the multi-sensorial ‘knowing-in-action’ of people with dis-abilities and the expertise of professional architects/designers. In this way, the research project aims to develop a more profound understanding of how the concept of Design for All can be realised in architectural practice. At least as important, however, is its contribution to innovation in architecture tout court. The research results are expected to give a powerful impulse to quality improvement of the built environment by stimulating and supporting the development of innovative design concepts.

Keywords: architectural design,disability
MICROARRAYS FOR THE DETECTION OF TOXIC ALGAE (MIDTAL)

Framework: FP7 — Cooperation
Programme: Environment (including Climate Change)
Destination: Environmental technologies
Action type: Collaborative project
Countries involved: United Kingdom,Italy,Sweden,Spain,Ireland,Norway,United Kingdom,Denmark,United States,United Kingdom,Spain
Call:  (FP7-ENV-2007-1, 2007)
Start date: 2008-09-01
End date: 2012-05-31
Duration (months): 45.0
Total project cost (EUR): 3312352.76
EU funding (EUR): 2234850.0
Participants: 11
Project status: CLOSED

Microalgae in marine and brackish waters of Europe regularly cause «harmful effects», considered from the human perspective, in that they threaten public health and cause economic damage to fisheries and tourism. Cyanobacteria cause similar problems in freshwaters. These episodes encompass a broad range of phenomena collectively referred to as «harmful algal blooms» (HABs). They include discoloration of waters by mass occurrences of microalgae (true algal blooms that may or may not be «harmful») to toxin-producing species that may be harmful even in low cell concentrations. A broad classification of HAB distinguishes three groups of toxic organisms. For adequate management of these phenomena, monitoring of microalgae is required. However, the effectiveness of monitoring programmes is limited by the fact that it is time consuming and morphology as determined by light microscopy may be insufficient to give definitive species and toxin attribution. Once cell numbers reach a threshold level, then shellfish are selected to toxin analysis by the mouse bioassay. The mouse bioassay is continued on a daily basis until no more toxin is detected. Molecular and biochemical methods are now available that offer rapid means of both species and toxin detection. In this project we will target rapid species identification using rRNA genes as the target. We include antibodies to specific toxins because even when cell numbers are very low, the toxins can be present and can be accumulated in the shellfish. Microarrays are the state of the art technology in molecular biology for the processing of bulk samples for detection of target RNA/DNA sequences.. The purpose of MIDTAL is to support the common fisheries policy to aid the national monitoring agencies by providing new rapid tools for the identification of toxic algae and their toxins so that they can comply with ECC directive 91/1491/CEE that can be converted to cell numbers and reduce the need for the mouse bioassay.

Keywords: microarrays,toxic algae,harmful algal blooms monitoring,rrna probes
Building a knowledge Repository for Occupational Well-being Economics Research (ROWER)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Coordination and support actions
Countries involved: Greece,Netherlands,Bulgaria,Türkiye,Romania
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-07-01
End date: 2011-09-30
Duration (months): 39.0
Total project cost (EUR): 866079.5
EU funding (EUR): 784791.64
Participants: 6
Project status: CLOSED

The proposed project aims to settle the fundamental basis that will enhance research on Occupational Health and Safety (OHS) Economics, which will allow for the development of policies regarding this issue. This goal will be achieved through a Support Action which will bring together the leading OHS Economists in Europe. Their knowledge will be gathered, interpreted and made available to the community through a dynamic on-line repository which will contain OHS Economics issues and will allow for discussion and communication of principles, case studies and management tools. Two specialised Working Group (WinG) meetings focusing on OHS Macroeconomics and OHS Microeconomics, respectively and two conferences on OHS Economics will attract new contributions in order to assess the impact of changing conditions of economy and labour on OHS.

Keywords: occupational,safety,health,well-being,economics
Fiber-top micromachined devices: ideas on the tip of a fiber (FTMEMS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Computer science and informatics
Countries involved: Netherlands
Call:  (ERC-2007-StG, 2007)
Start date: 2008-06-01
End date: 2013-05-31
Duration (months): 60.0
Total project cost (EUR): 1799915.0
EU funding (EUR): 1799915.0
Participants: 2
Project status: CLOSED

Fiber-top sensors (D. Iannuzzi et al., patent application number PCT/NL2005/000816) are a new generation of miniaturized devices obtained by carving tiny movable structures directly on the cleaved edge of an optical fiber. The light coupled into the fiber allows measurements of the position of the micromechanical parts with sub-nanometer accuracy. The monolithic structure of the device, the absence of electronic contacts on the sensing head, and the simplicity of the working principle offer unprecedented opportunities for the development of scientific instruments for applications in and outside research laboratories. For example, a fiber-top scanning probe microscope (also in the form of a PenFM, where a fiber-top atomic force microscope would be incorporated in a pen-like stylus) could be routinely used in harsh environments and could be easily handled by untrained personnel or through remote control systems – a fascinating perspective for utilization, among others, in surgery rooms and space missions. Similarly, the development of fiber-top biochemical sensors could be exploited for the implementation of portable equipment for in vivo and Point of Care medical testing. Fiber-top sensors could be used for the measurement of parameters of medical relevance in interstitial fluid or in blood – an interesting opportunity for intensive care monitoring and early detection of life-threatening diseases. This scenario calls for a coordinated research program dedicated to this novel generation of devices. It is my intention to forge a laboratory gravitating around fiber-top technology. My group will have the opportunity to pioneer this research area and to become the reference point in the field, on the forefront of an emerging subject that might represent a major breakthrough in the future development of micromachined sensors.

Keywords: atomic force microscopy,microelectromechanical systems,optical fiber sensors,instrumentation
Pathophysiology of rare diseases due to ciliary dysfunction: nephronophthisis, Oral-facial-digital type 1 and Bardet-Biedl syndromes (EUCILIA)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Italy,United Kingdom,Germany,Italy
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-02-01
End date: 2011-01-31
Duration (months): 36.0
Total project cost (EUR): 3848873.0
EU funding (EUR): 2930300.0
Participants: 4
Project status: CLOSED

Primary cilia have been recognized on nearly all-mammalian cells. Emerging data suggest that they act as cellular antennae with diverse motility and sensory functions, detecting a wide variety of signals. As such, defects in cilia formation or function have profound effects on the development of body pattern and the physiology of multiple organ systems. Ciliary defects underlie a wide range of human disorders, including the rare and heritable Bardet-Biedl (BBS), Oro-facial-digital type 1 (OFD1) and nephronophthisis (NPHP) syndromes. Each of these disorders present with defining features but all are characterized by polycystic renal disease. The proteins encoded by the genes responsible for these disorders, as well as those implicated in heritable forms of cystic kidneys, are all located to the cilium/basal body/centrosome complex, suggesting that ciliary dysfunction might be the unifying pathogenic concept underlying cystic kidney disease. However, the molecular mechanisms remain undetermined. We propose to use BBS, OFD1 and NPHP syndromes as model systems to study the physiological role of primary cilia, with special emphasis on their role in the genitourinary tract and in the development of renal cysts. The experimental plan proposes to generate and make available to the scientific community in vitro and in vivo models to study the physiological role of primary cilia and of OFD1, BBS and NPHP proteins in the formation and function of the primary cilium. These tools will allow the analysis of the ciliary protein interaction network and of the downstream pathway in the absence of BBS, OFD1, or NPHP. Finally, we propose to identify and evaluate potential therapeutic agents. The biological relevance and significance of the results obtained will have implications far beyond the rare OFD1, BBS and NPHP patients and may shed light on the mechanisms underlying the role of primary cilia in polycystic kidney disease paving the way to possible new therapeutic approaches.

Keywords: rare diseases,polycystic kidney,cilia,animal models