Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Targeting LRP5 to Increase Bone Formation in Osteoporosis (TALOS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,Belgium,United Kingdom,Germany,Switzerland,France,Netherlands,Germany
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-05-01
End date: 2011-04-30
Duration (months): 36.0
Total project cost (EUR): 3898406.0
EU funding (EUR): 2904304.0
Participants: 9
Project status: CLOSED

The balance between bone resorption and bone formation determines the mass and structural integrity of the skeleton and is disturbed in osteoporosis. In contrast to the molecular mechanisms regulating bone resorption, knowledge of the mechanisms regulating bone formation is limited. A recent breakthrough has been the identification of a link between bone mass in humans with rare bone disorders and gain- or loss-of function mutations of the Wnt co-receptor LRP5 or the Wnt antagonist sclerostin. The mechanism, however, underlying these actions on Wnt signalling is unclear. We propose studies with the following specific aims: i) to characterize the clinical, bioschemical, radiological and histological features of patients with sclerosteosis, van Buchem disease and other craniotubular hyperostoses ii) to determine the genetic defect in patients with craniotubular hyperostoses and establish putative genotype-phenotype correlations iii) to unravel the molecular mechanism of the inhibitory action of sclerostin on bone formation and to determine how genetic variations in SOST, LRP5 and Wnt signalling pathway modify bone architecture and remodelling iv) to reveal the pattern of sclerostin expression by analysis of the SOST promoter and by histomorphometry of human bone biopsies v) to identify and characterize co-factors of the LRP5 signalling and their in vivo actions in relevant animal models vi) to identify epitopes in sclerostin that mediate the interaction with LRP5, raise peptide-bound protein mimics and test them in vitro and in animal models of bone loss. These studies will not only help understanding the molecular basis of critical signalling pathway in bone formation but will also provide insight into normal and disturbed modulation of bone remodelling. Moreover, they will help in the design of bone forming interventions for the treatment of patients with osteoporosis.

Keywords: lrp5,osteoporosis,bone formation,wnt signaling,sost
MicroRNAs and Cancer: From Bench to Bedside (ONCOMIRS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Belgium,Spain,Israel,Denmark,France,Germany,Denmark
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-02-01
End date: 2013-01-31
Duration (months): 60.0
Total project cost (EUR): 4278007.11
EU funding (EUR): 2992227.0
Participants: 7
Project status: CLOSED

Although studies addressing their role in cancer pathogenesis are at an early stage, it is apparent that specific microRNAs (miRs) and molecules involved in their biogenesis contribute to tumorigenesis. The ONCOMIRS consortium proposes a natural succession of four experimental strategies. Fist, we will DISCOVER and unveil novel miRs and components of their biogenesis machinery and investigate links between these molecules and human cancers. Secondly, we will CONNECT the information obtained on deregulated miRs with known cellular pathways involved in cancer, such as the p53 tumour suppressor pathway. This will be conducted using both forward experimentations, in which targets mRNA are experimentally identified for a number of miR aetiologically related to cancer, and reverse experimentations in which mouse models and cell lines with abrogated tumour suppressor pathways or activated oncogenes are used. To establish a causal relationship between dysregualted miRs and cancer development we will MODEL the tumorigenic processes in mice lacking or overexpressing particular miRs. Finally, since the specificity and potency of some miRs suggest that they might be promising as THERAPEUTIC agents, these models will be used in conjunction with other cancer models to explore miR-based therapeutic strategies.

Keywords: ncrnas,micrornas,cancer,mouse models,p53,therapy
Empowering Biomedical and Bioengineering SMEs to promote participation in FP7 projects (SM-BIO-POWER)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Coordination and support actions
Countries involved: Israel,Germany,United Kingdom,Lithuania,Italy,Lithuania,Germany,Switzerland,United Kingdom
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-09-01
End date: 2011-06-30
Duration (months): 34.0
Total project cost (EUR): 1229011.2
EU funding (EUR): 1129999.0
Participants: 11
Project status: CLOSED

The SM-BIO-POWER project aims to stimulate, promote and support the participation of high-tech, research intensive SMEs operating in the medical technology and biomedical engineering sectors of the health field for long term research interest and increased participation in the context of FP7 European Research activities. The proposed project is largely based on the outcomes and the experience gained in a previous project (ETI-CT-2005-023401-SME-MPOWER) running since November 2005 and ending October 2007 (coordinated by Fraunhofer Institute for Factory Automation and Operation). The objective of the predecessor project (&quot;the predecessor&quot; from here on) was to “demonstrate how high-tech SMEs can be empowered long-term for international R&amp;D activities, and enhance the number of SME driven innovation projects in the context of European Research through the creation of a uniquely resourced pan-European Learning Community of Innovation Coaches and SME Intermediaries”. This was done with specific, while not exclusive focus is the Manufacturing Sector. Core members of the predecessor are also core members in this proposal. They will provide the infrastructure that has been developed and the accumulated experienced gained in the predecessor for the benefits of this project. As a result, this project will be mainly targeting deployment of the suggested processes, rather than developing them. The project is aiming at dealing with two painful problems that creates a substantial gap between the Framework Programme structure and rules on one hand, and the ability of the SMEs to respond/deal and comply with these regulations in a timely and efficient fashion, on the other hand.

Keywords: peer-net coaching sme promotion self-sustained biomedical bioengineering
Pathophysiology and natural course of autoimmune adrenal failure in Europe (EURADRENAL)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Norway,Sweden,Italy,United Kingdom,Germany,Poland,Sweden,United Kingdom,Switzerland,United Kingdom
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-04-01
End date: 2012-03-31
Duration (months): 48.0
Total project cost (EUR): 3968171.0
EU funding (EUR): 2999931.0
Participants: 12
Project status: CLOSED

Autoimmune Addison’s disease (AAD) is an endocrine disease resulting from the immune system’s destruction of hormone producing cells in the adrenal cortex. Diagnosis is frequently first established after a life-threatening adrenal crisis, often resulting in untimely fatalities. The disease is rare, more common in women than in men, and also affects children. AAD very frequently occurs with other autoimmune diseases, such as type 1 diabetes mellitus, autoimmune thyroid disease and/or premature ovarian failure. Based on a European network of patient registry and biobanks, a translational approach using genetics, immunology, clinical management, and epidemiology, the project aims to unravel the pathogenesis and natural course of AAD, ultimately to improve diagnosis and treatment as well as to offer strategies for disease prevention. The consortium capitalises on the joint cutting edge expertise of leading European investigators covering all these fields. Exploiting these resources, we will describe the natural course of the disease with focus on factors limiting quality of life, and identify and characterise the disease-causing genes, using the corresponding disease in a spontaneous dog model and a gene targeted mouse model. In parallel, the cellular and molecular mechanisms of autoimmunity directed at the adrenal cortex will be unravelled both in humans with ADD and in the genetic mouse model. Together, these efforts will increase our still incomplete understanding of pathogenic pathways operational in AAD and pave the way for new therapies of this debilitating disorder. Moreover, clinical studies will be performed to evaluate more physiological and personalised treatment with cortisol also aimed at prevention. As an autoimmune model disease the results of the project will not only lead to the development of novel diagnostic and therapeutic interventions for Addison patients, but also increase our understanding of the pathogenesis of autoimmune diseases in general.

Keywords: adrenal,autoimmune,polyendocrine,addison's diseaes
Engineering zinc fingers to target cancer hub genes (ZINC-HUBS)

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: United Kingdom,Spain
Call:  (ERC-2007-StG, 2007)
Start date: 2008-10-01
End date: 2014-09-30
Duration (months): 72.0
Total project cost (EUR): 1327689.0
EU funding (EUR): 1327689.0
Participants: 2
Project status: CLOSED

For the last ten years, protein engineering technologies have been developed to make zinc finger peptides to recognise a wide variety of user-defined DNA sequences. This has enabled the construction of synthetic transcription factors that can upregulate or repress target genes at will. More recently, synthetic zinc fingers have been linked to nucleases to direct double stranded breaks at desired loci within genomes. These breaks increase the efficiency of homologous recombination so that, by providing an exogenous repair sequence, it is possible to repair or mutate endogenous genes. Although zinc finger engineering has reached a state of maturity, there are very few groups in the world who have the technical know-how to adopt this technology, and this has delayed general uptake. We will use the expertise we have developed, in both zinc finger engineering and gene repair, to construct zinc finger proteins to recognise some of the most highly-connected (and widely-studied) genes in biology. This will serve as a toolkit for the research community to target hub genes and either mutate or repair them. As a starting point we propose to target the following hub genes: TBP (TATA-binding protein), p53, p300, RXR, pRB, RelA, c-jun, c-myc, and c-fos. These genes are the most connected hubs in the human transcription factor network (TRANSFAC 8.2 database) and their mutants are associated with a variety of diseases. We will engineer and characterise zinc finger proteins that recognise these DNA sequences in vitro and induce gene repair in vivo. For example, this will allow cancer cell lines to have particular oncogenes repaired or mutated, within the context of all the other mutations that have been accrued during the process of oncogenesis. This will help to characterise the contribution of network nodes and hubs to the observed phenotypes. Ultimately, some of the gene repair peptides we create will have therapeutic potential, as well as providing tools for systems biology.

Keywords: systems biology synthetic biology
Novel MS-based strategies to Discover and Evaluate Cancer Biomarkers in urine: Application to Diagnosis of Bladder Cancer (DECANBIO)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,Greece,Switzerland,Spain,Luxembourg,Germany
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-03-01
End date: 2012-07-31
Duration (months): 53.0
Total project cost (EUR): 3910866.56
EU funding (EUR): 2907412.0
Participants: 9
Project status: CLOSED

In clinical studies, proteomics and transcriptomics allow the comparison of samples from different patients and hold special promise for the discovery of novel biomarkers and the development of “personalized medicine” approaches. Yet, translating recent discoveries into daily medical practice takes time and despite intensified researchers’ interest and investments, the rate of introduction of novel biomarkers in clinical practice is extremely disappointing. The main aim of DECanBio is to implement a strategy for protein biomarker discovery and validation relying on the use of “state of the art” mass spectrometry instrumentation for quantitative analysis of proteins. For the first time, the potential of MRM-Mass Spectrometry (MRM-MS) will be tested in the scope of a large scale validation protocol of cancer protein biomarkers. This analysis will be performed in parallel to the application of miniaturized high-throughput ELISA tests for protein quantification. DECanBio strategy will be applied to issues related to bladder cancer. Specifically, a restricted number of urinary protein biomarkers enabling the detection of recurrences during the monitoring period of patients treated for bladder tumour will be validated. The work will be performed in priority for the follow-up of low-grade superficial bladder tumours (Ta stage), which, after initial resection (without BCG therapy), are likely to evolve towards remission, recurrence, or progression to a high-grade tumor. The MRM and ELISA tests developed herein aim at the high-throughput quantification of these markers in urine. Collectively, the project has the ambition to settle a whole experimental pipe-line, from the search for new bladder cancer biomarker candidates, to their thorough evaluation and validation in clinical environment. We anticipate that the tools and knowledge that will be developed here will greatly facilitate translational studies for other diseases as well.

Keywords: biomarkers,proteomics,transcriptomics,bladder cancer,diagnosis,elisa,mass spectrometry,electrophoresis
OrganoCATAlytic approaches towards easily synthesized, economical, and high yielding oseltamivir derivatives (CATAFLU.OR)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Italy,Slovakia,Germany,China,Finland
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-04-01
End date: 2011-09-30
Duration (months): 42.0
Total project cost (EUR): 2965217.05
EU funding (EUR): 2300000.0
Participants: 7
Project status: CLOSED

Despite widespread immunization, influenza still kills thousand of people, and costs to US, Europe and Asia enormous amount of money in term of healthcare expenses and productivity losses. While immunization remains an important approach to prevent influenza, small-molecule antiviral agents represent a novel opportunity for effective prevention and therapy of flu. Inhibitors of neuraminidase, essential enzyme for viral replication in all three classes of influenza viruses, has been recently found. Two of these inhibitors have reached the market, namely, zanamivir (GSKBs Relenza (1) in July 1999, and oseltamivir phosphate (Gilead Bs Tamiflu (2), also marketed by Roche) in October 1999. The recent healthy problem related to avian flu, has increase the public demand for stockpiles of Tamiflu, both as a reasonable frontline therapy against a possible flu pandemic and as a preventive agent. However, natural sources of drug (Shikimic acid) are scarcely, and increasing demand for oseltamivir phosphate has placed further pressure on Roche and the chemical community in general to develop new routes to the drug that do not involve complex natural products. In addition, the described synthesis are expensive and difficult. Moreover, in this synthesis use of hazardous azide-based reagents was necessary. New routes to Tamiflu have been recently described, but more than 12 steps in one case and 17 in another are needed. In order to find new drug candidates, cut the drug costs and improving availability as well as efficiency, new chemical synthesis are necessary. We propose a new domino reaction based on an organocatalytic approach to the synthesis of new Tamiflu derivatives. The chemistry involved in this project is easy to perform, and well adapt to industrial contest. Moreover, new chemical structures will be prepared and evaluated as potential drug against virulent and mutated flu viruses.

Keywords: influenza,tamiflu,neuraminidase inhibitors,influenza pandemic,shikimic acid,oseltamivir phosphate,new drugs,organocatalysis
European initiative to improve knowledge, treatment and survival of haemophagocytic syndromes in children (CUREHLH)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,Italy,Germany,Germany,United Kingdom,Sweden,France,Italy,Italy
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-06-01
End date: 2011-05-31
Duration (months): 36.0
Total project cost (EUR): 3917550.34
EU funding (EUR): 2994942.0
Participants: 9
Project status: CLOSED

Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening inherited immune disorder of early childhood characterised by an uncontrolled immune response. Three disease causing genes have been identified in about half of the patients. Diagnosis is difficult, pathophysiology poorly understood, and treatment unsatisfactory with about 40% of the children dying from treatment failure or toxicity. All European scientists active in research and treatment of HLH have joined in a consortium to enforce collaboration, combine the various expertises, and provide access to material and data. In vitro studies and several murine models for HLH and diseases predisposing to HLH, will be used to get more insight into the pathophysiology of the diverse genetic defects. Studies will address the role of triggers and antigen-presenting cells, the influence of cytokines in the initiation and propagation of the uncontrolled immune response, the interaction of immune effector cells and soluble factors, and the mechanism of cytotoxicity in lymphocytes and natural killer cells. Data about geno-phenotype will be combined to evaluate how known and unknown genetic defects reflect on the clinical course and immunophenotype of the patients. A diagnostic algorithm, incorporating knowledge from the known defects, will be developed and optimised in all countries to facilitate earlier and reliable diagnosis, and to separate patients with unknown defects or acquired HLH. The identification of risk factors for treatment failure and toxicity will be used to design improved treatment strategies. An experimental treatment will be tested in a murine model and will be the basis for a less toxic treatment in the future. Earlier diagnosis, better insight into the pathophysiology, and development of less toxic treatments are the steps towards a higher cure rate in HLH. In a rare disease as HLH, only combined efforts on an European-wide level will be able to achieve these goals.

Keywords: haemophagocytosis,histiocytosis,immunodeficiency,genetic disease,children,murine model
The hidden life of our genes - the promise of epigenetics a 52 minutes documentary film for televisions. (EPIGENETIC FILM)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Coordination and support actions
Countries involved: France
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-01-01
End date: 2009-05-31
Duration (months): 17.0
Total project cost (EUR): 378663.0
EU funding (EUR): 375000.0
Participants: 1
Project status: CLOSED

The project aims at giving citizens accessible information on European research on Epigenetics which exerts genuine impacts on our everyday life but which is not yet well known of the general public. It consists in producing a 52' film and to disseminate this film toward european television channels. The film also aims at highlighting the important involvement of european research in this field and at helping the scientists who take an active part in european epigenetics network of excellence to get access to the audiovisual medias in order to deliver their message in a simple and attractive form.

Keywords: epigenetics - the epigenome network of excellence - documentary - television
Genetic Analysis of the host-pathogen interaction in tuberculosis (TB-EURO-GEN)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: United Kingdom,United Kingdom,Sweden,Germany,Germany
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-03-01
End date: 2011-08-31
Duration (months): 42.0
Total project cost (EUR): 3958636.8
EU funding (EUR): 2838264.0
Participants: 5
Project status: CLOSED

We propose to extend an existing collection of DNA extracts from TB patients and their corresponding TB DNA to establish the world’s largest resource of extracts from a population of TB patients and 5000 ethnically matched healthly controls. The bank will comprise 5000 DNA host DNA extracts paired the DNA and cultures of the strain of Mycobacterium tuberculosis causing their disease. We will perform a genome-wide scan to discover human genes predisposing to TB. We will then localise causal variants and study their role in a case-control population TB sample from another high incidence country in Africa ,Ghana. We will extensively characterise TB strains from a population in Russia using spoligotyping, minisatellite analysis, and SNP analysis of genes putatively associated with virulence and analyse the host-pathogen interaction identifying mycobacterial genes affecting the course of TB, the innate response to TB and outcome at a genetic level. Based on the existing collection of matched host-pathogen DNA we will perform functional experiments of the role of identified mycobacterial factors such as PE variants and the effect of this variation on aspects of innate immunity as influenced by newly-identified TB-associated genes.

Keywords: tuberculosis,human susceptibility,virulence gene polymorphisms