Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Immunoglobulin IgY pseudomonas A clinical trial for cystic fibrosis treatment (IMPACTT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Sweden,Germany,Denmark,Lithuania,Germany,Sweden,France,Italy
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2011-01-01
End date: 2016-12-31
Duration (months): 72.0
Total project cost (EUR): 7055166.59
EU funding (EUR): 5376180.0
Participants: 10
Project status: CLOSED

Cystic Fibrosis (CF) is a chronically debilitating and life threatening medical condition. Respiratory insufficiency and complications of chronic lung infection lead to long term reduction in quality of life and health and even to premature death. Chronic bacterial infections with Pseudomonas aeruginosa (PA), Staphylococcus aureus and Haemophilus influezae are typical for CF and repeated courses of antibiotics in heavy doses has more than doubled the median survival age. No preventive or eradicative treatments of PA infection in the lungs exist today. The most significant bacterial pathogen associated with CF pulmonary disease is PA. PA is an opportunistic, life-threatening gram-negative bacteria which produces various immune modulatory products enabling it to survive in the lungs and cause morbidity and mortality. CF patients are particularly at risk of infection due to the viscous mucus lining their airways, which compromises their respiratory function. The European Medicines Agency granted “Anti-pseudomonas IgY” an Orphan Drug Designation in September 2008, and paediatric CF product development was encouraged. The IMPACTT project will perform a clinical phase III trial, to demonstrate the critical preventive and therapeutic effects of this pioneering intervention therapy for the fatal chronic infection of Pseudomonas aeruginosa in CF patients. The project mobilises the critical mass of experts from academia, patient organisations, clinical trials managers, clinicians and industry aiming to eradicate PA infection in CF patient lungs and thereby alleviate the negative impact of PA on the quality of life of CF patients and their families. Despite good results with antibiotics, continuous pulmonary deterioration and death of the CF patient is a reality. Alternative therapeutic strategies are badly needed. Our phase I and II clinical studies prove that a single daily gargle with the proposed Anti-Pseudomonas IgY solution significantly improves the condition.

Keywords: clinical trial,cystic fibrosis,anti-pseudomonas igy
The economic evaluation of end of life care (ECONENDLIFE)

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: United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2015-09-30
Duration (months): 54.0
Total project cost (EUR): 999177.0
EU funding (EUR): 999177.0
Participants: 1
Project status: CLOSED

Making choices about the health care that we provide in society is a fundamental and unavoidable issue. Economic evaluation aids this decision-making by supplying information about costs and benefits of different interventions. For end of life care, however, current evaluative frameworks are inadequate because they focus only on health and only on the patient. Amartya Sen’s capability approach offers an alternative and appropriate framework for evaluating end of life care and this programme aims to build on my ground-breaking work in the application of Sen’s approach to measurement within economic evaluation. Six key tasks will be undertaken: (i) defining the ‘end of life’ period using semi-structured interviews with key stakeholders; (ii) assessing the construct validity and sensitivity to change of a descriptive system for evaluating capabilities related to end of life care; (iii) eliciting values for this descriptive system from the general public and patients at the end of life using the best-worst scaling technique; (iv) developing a descriptive system to evaluate the impact on families’ capabilities of end of life care, using in-depth interviews to develop conceptual attributes; (v) conducting exploratory theoretical and methodological work on weighting across measures; and (vi) exploring views of the public and key stakeholders about appropriate decision-rules for end of life care, using a combination of focus groups and in-depth interviews. The work involves frontier research at the interface between health, economics and human development. It will address the significant methodological issues associated with the economic evaluation of end of life care and so advance the state-of-the-art to a point where robust economic evaluation of end of life care is feasible.

Keywords: health economics,end of life care
Dissecting a Novel Mechanism of Cell Motility (DOME)

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: France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1437693.0
EU funding (EUR): 1437693.0
Participants: 1
Project status: CLOSED

Cell motility is essential for many biological processes, including development and pathogenesis. Thus, the molecular mechanisms underlying this process have been intensively studied in many cell systems, for example, leukocytes, amoeba and even bacteria. Intriguingly, bacteria are also able to move across solid surfaces (gliding motility) like eukaryotic cells by a process that has remained largely mysterious. The emergence of bacterial cell biology: the discovery that the bacterial cell also has a dynamic cytoskeleton and specialized subcellular regions now provides new research angles to study the motility mechanism. Using cell biology approaches, we previously suggested that the mechanism may be akin to acto-myosin-based motility in eukaryotic cells and proposed that bacterial focal adhesion complexes also power locomotion. In this project, we propose two complementary research axes to define both the mechanism and its spatial regulation in the cell at molecular resolution. Using the model motility bacterium Myxococcus xanthus, we first propose to develop a “toolbox” of biophysical and cell biology assays to analyze the motility process. Specifically, we will construct a Traction Force Microscopy assay designed to image the motility forces directly by live moving cells and use microfluidics to quantitate the secretion of a mucus that may participate directly in the motility process. These assays, combined with a newly developed laser trap system to visualize dynamic focal adhesions in the cell envelope, will be instrumental not only to define new features of the motility process, but also to study the function of novel motility genes which may encode the components of the elusive motility engine. This way, we hope to establish the mechanism and structure function relationships within an entirely novel motility machinery. In a second part, we propose to investigate the mechanism that controls a polarity switch, allowing M. xanthus cells to change their direction of movement. We have previously shown that dynamic motility protein pole-to-pole oscillations convert the initial leading cell pole into the lagging pole. Here, we propose that like in a eukaryotic cells, a bacterial counterpart of small GTPases of the Ras superfamily, MglA controls the polarity cycle. To test this hypothesis, we will study both the MglA upstream regulation and the MglA downstream effectors. We thus hope to establish a model of dynamic polarity control in a bacterial

Keywords: bacteria,cytoskeleton,motility,cell polarity,small gtpase
Single-molecule analysis of DNA polymerase in vitro and in vivo: a machine in action (POLMACHINE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: ERC Starting Grant Interdisciplinary Panel
Countries involved: United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-02-01
End date: 2016-01-31
Duration (months): 60.0
Total project cost (EUR): 1493413.0
EU funding (EUR): 1493413.0
Participants: 1
Project status: CLOSED

DNA polymerases are dynamic molecular machines that faithfully copy genetic information during DNA replication and DNA repair. DNA polymerases use the information in a DNA template strand to synthesize a complementary copy by adding nucleotides to the 3 -end of a DNA primer. Extensive analysis has provided information on the structural organization of polymerases and led to proposals of a general scheme for nucleotide addition. However, there are many unanswered questions; we cannot really claim that we understand how the polymerase machine works in detail and how its function is modulated by its substrates, or by the intracellular environment of cells. One of the main reasons lies in the fact that crystal structures cannot directly capture the dynamics of multi-step processes, since the structures are static snapshots of structural states. Another limitation arises from the difficulty of interpreting biochemical studies of complex mechanisms, because of complications due to ensemble- and time-averaging of the observed signals. We propose to overcome these limitations by studying DNA synthesis by a proofreading DNA polymerase (Pol I) through direct, real-time observation of its movements and interactions at the single-molecule level. We will study mechanisms of fidelity through comparisons involving mutant polymerases, mispaired nucleotides, or partially mispaired DNA, and make comparisons with RNA polymerases. We will also study the conformation and subcellular localisation of Pol I in bacterial cells. Our specific aims are: 1. To study conformational transitions of the DNA polymerase I fingers subdomain 2. To study translocational dynamics of DNA polymerase I on DNA substrates 3. To study the coupling of DNA polymerase I motions during nucleotide addition 4. To study conformational dynamics of DNA polymerase I during nick translation 5. To study the subcellular localization and conform

Keywords: dna polymerase,molecular machines,mechanism,protein dynamics,molecular motions,conformational changes,single-molecule studies,fret,super-resolution imaging,sub-cellular localization
Role of Endoplasmic Reticulum Stress in dendritic cells and immune-mediated lung diseases (ERSTRESS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Belgium
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2015-11-30
Duration (months): 60.0
Total project cost (EUR): 1499580.0
EU funding (EUR): 1499580.0
Participants: 1
Project status: CLOSED

My overall aim is to understand the physiologic and medical importance of lung dendritic cells (DC) and to define the suitability of inhibitors of their function for the treatment of inflammatory lung diseases like asthma and COPD. Lung dendritic cells (DC) play crucial roles in the regulation of lung immunity. We still do not fully understand how they get activated in response to different types of environmental triggers like allergens, cigarette smoke and pathogens. Although recognition of conserved motifs by pattern recognition receptors on DCs could be a key event, these stimuli are also accompanied by accumulation of unfolded proteins in the endoplasmic reticulum (ER). Cells respond by mounting the unfolded protein response (UPR) that acts to ameliorate protein folding, but intersects with metabolism, induction of alarm signals and cellular suicide mechanisms. I hypothesize that the presence of unfolded proteins and ER stress in DCs is a crucial endogenous danger signal that is vital to understanding their biology and their involvement in inflammatory lung diseases. My specific aims are to : 1.define the fine tuning of ER stress pathways in various lung DC subsets in health and disease 2. define the specific role of ER stress proteins XBP1, JIK and ORMDL3 in DCs 3. test if interfering with ER stress pathways alters the course of inflammatory lung disease To approach these aims, I have developed mouse models of lung disease that are centered around lung DCs and where ER stress pathways can be genetically deleted. Using a combination of cell biological and immunological techniques I hope to achieve definitive answers as to how ER stress pathways regulate the function of DCs. Manipulation of ER stress pathways by drugs will have a major impact on very common diseases like diabetes, cardiovascular and neurodegenerative disease. Through the current proposal, I hope to extend this exciting field to lung biology.

Keywords: dendritic cells,danger signals,asthma
Priming epithelial cell activation to regenerate the lung (PEARL)

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-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 1291670.0
EU funding (EUR): 1291670.0
Participants: 1
Project status: CLOSED

Chronic obstructive pulmonary disease (COPD), a global health problem, will be the third leading cause of death by 2020. No effective therapy exists for COPD, which is characterized by a progressive loss of lung tissue, in particular functional alveolar epithelium, due to the inability of the lung to regenerate. Thus, regeneration of functional lung tissue would be a tremendous step forward, which has not been demonstrated as of yet. The alveolar epithelium is essential for normal lung function and composed of alveolar type I (ATI) and type II (ATII) cells. ATII cells serve as progenitors for alveolar epithelial restoration via differentiation into ATI cells. Induction of lung regeneration requires a tight interplay between initiating and differentiating factors acting on the alveolar epithelium. The overall aim of this proposal is to explore the regenerative potential of the adult human lung, driven by the alveolar epithelium. We will utilize an ex vivo lung regeneration model, characterize ATI/II cells in diseased lungs, and explore novel initiating and differentiating factors in vivo and ex vivo. WNT/²-catenin signaling is a promising initiating factor for lung regeneration. We have recently demonstrated a crucial role of WNT/²-catenin signaling in alveolar epithelial cell repair in lung disease. Further, embryos lacking WNT2/2b expression exhibited complete lung agenesis, demonstrating the requirement of WNT/²-catenin signaling in lung generation. We will explore WNT/²-catenin signaling in ATI/II cells, and the regenerative potential thereof. We will analyze the ATI/II cell phenotype in mouse and human COPD specimen, to identify novel differentiation factors facilitating lung regeneration. We will consolidate our findings by testing the therapeutic applicability of initiating and differentiating factors in COPD in our ex vivo human lung regeneration model. This will lead to reliable and validated results that will be successfully translated into the clinic.

Keywords: chronic lung disease,alveolar epithelial cell activation,wnt-beta catenin signaling,human ex vivo lung regeneration model
Cold Carbon Catabolism of Microbial Communities underprinning a Sustainable Bioenergy and Biorefinery Economy (3CBIOTECH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Ireland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 1499796.82
EU funding (EUR): 1499796.82
Participants: 1
Project status: CLOSED

The applicant will collaborate with Irish, European and U.S.-based colleagues to develop a sustainable biorefinery and bioenergy industry in Ireland and Europe. The focus of this ERC Starting Grant will be the application of classical microbiological, physiological and real-time polymerase chain reaction (PCR)-based assays, to qualitatively and quantitatively characterize microbial communities underpinning novel and innovative, low-temperature, anaerobic waste (and other biomass) conversion technologies, including municipal wastewater treatment and, demonstration- and full-scale biorefinery applications. Anaerobic digestion (AD) is a naturally-occurring process, which is widely applied for the conversion of waste to methane-containing biogas. Low-temperature (<20 degrees C) AD has been applied by the applicant as a cost-effective alternative to mesophilic (c. 35C) AD for the treatment of several waste categories. However, the microbiology of low-temperature AD is poorly understood. The applicant will work with microbial consortia isolated from anaerobic bioreactors, which have been operated for long-term experiments (>3.5 years), and include organic acid-oxidizing, hydrogen-producing syntrophic microbes and hydrogen-consuming methanogens. A major focus of the project will be the ecophysiology of psychrotolerant and psychrophilic methanogens already identified and cultivated by the applicant. The project will also investigate the role(s) of poorly-understood Crenarchaeota populations and homoacetogenic bacteria, in complex consortia. The host organization is a leading player in the microbiology of waste-to-energy applications. The applicant will train a team of scientists in all aspects of the microbiology and bioengineering of biomass conversion systems.

Keywords: biorefinerery,bioenergy,microbial ecology,methanogenesis,anaerobic digestion,diagnostic tools.
Mechanisms of the Development of ALLergy (MEDALL)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,Germany,Netherlands,Belgium,Finland,Poland,Norway,Austria,Switzerland,Sweden,Germany,Netherlands,United Kingdom,United States,Belgium,Denmark,Spain,Italy
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-12-01
End date: 2015-05-31
Duration (months): 54.0
Total project cost (EUR): 15659041.05
EU funding (EUR): 11990939.0
Participants: 23
Project status: CLOSED

Causes explaining the epidemic of IgE-associated (allergic) diseases are unclear. MeDALL (Mechanisms of the Development of Allergy) aims at generating novel knowledge on mechanisms of allergy initiation, in particular in childhood. To understand how a complex network of genetic and environmental factors leads to complex allergic phenotypes, a novel stepwise, large and integrative translational approach is needed. MeDALL includes experts in allergy, epidemiology, genetics, immunology, biology, animal models, biochemistry and systems biology combining strengths of ongoing EU projects. Classical phenotypes (expert-based) and novel phenotypes of allergy (hypothesis-free statistical modelling) are compared. Population-based data are collected from a cross-sectional study (Karelia) and existing birth-cohorts followed using a common protocol. IgE to foods and inhalants are tested using component-resolved diagnosis across Europe in populations. Biomarker profiles (“fingerprints”) are extensively assessed using epigenetics, targeted proteomics and unbiased transcriptomics in a subsample of the study population. Those associated with allergic phenotypes are validated in large study populations. Relevant fingerprints are combined into network biomarker phenotype “handprints” using a systems biology approach and validated in a sufficiently powered sample. Animal studies and in vitro human immunology reinforce the validation. This information coupled with classical and novel phenotypes characterize environmental protective and susceptibility factors of allergy and risk groups. Results are fitted into new integrative complex mathematical models to establish suitable biomarkers for early diagnosis, prevention and targets for therapy of allergy-associated diseases such as asthma and atopic dermatitis. Ethics and gender are considered. MeDALL aims at improving health of European citizens, Europe competitiveness and innovative capacity while addressing global health issues.

Keywords: allergy,asthma,atopic dermatitis,biomarkers,epidemiology,food allergy,ige,immunology,prevention,systems biology
Pharmacodynamic Approaches to Demonstration of Disease-Modification in Huntington’s Disease by SEN0014196 (PADDINGTON)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,United Kingdom,Italy,Poland
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-07-01
End date: 2013-12-31
Duration (months): 42.0
Total project cost (EUR): 8589885.35
EU funding (EUR): 5816313.6
Participants: 5
Project status: CLOSED

The Consortium will undertake clinical research activities aimed at ascertaining feasibility of a range of pharmacodynamic readouts for use in the clinical development of SEN0014196 to demonstrate the disease-modifying properties of the compound in Huntington’s Disease. SEN0014196 is a novel and selective SirT1 inhibitor, currently in Phase I clinical development, and enjoys Orphan Status in the EU as of September 2, 2009. A multi-factorial approach will be used, including assessment of both novel and compound-specific measures of molecular action as well as previously identified predictors of disease progression. The translational approaches addressed by this project are instrumental in the progression of SEN0014196 to clinical proof-of-concept and, if successful, will play a pivotal role in patient stratification and outcomes research. The Consortium will comprise four partners, all with a proven track-record in Research and Development in the Huntington’s Disease area. All Partners are based within the EU.