Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
A Novel Drug Targeting Strategy for the Treatment of Inflammatory Bowel Disease: A Molecular Biopharmaceutical Approach (TARGETIBDBYPLA2)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Israel
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-05-01
End date: 2015-04-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

A molecular approach will be applied to mechanistically target drugs - by exploiting phospholipase A2 (PLA2) - to diseased tissues in inflammatory bowel disease (IBD). PLA2 hydrolyses the sn-2 fatty acyl bond of phospholipids (PL), liberating a fatty-acid and a lysophospholipid. We have shown that by substituting the sn-2 fatty-acid of the PL with a drug, PLA2 may be exploited as a prodrug activating enzyme, liberating the free drug from the PL-complex. Further, PLA2 affinity to the prodrug and the intestinal permeability of the whole prodrug can be manipulated by the conjugate design. PLA2 expression/activity has been shown to be significantly elevated in tissues of patients with IBD - both Crohn’s disease and ulcerative colitis. We posit that since the activation of the PL-drug conjugate is PLA2 mediated, increased PLA2 levels in the diseased tissue will lead to increased free drug in the actual diseased tissues, accompanied by decreased drug levels in non-diseased areas, resulting in extended therapeutic index and improved drug therapy. The proposed research will mechanistically facilitate specific targeting of 5-aminosalicylic acid (5ASA) for proof-of-concept. However, targeting of other drugs will be enabled by the core approach developed in this research. The specific aims are: 1) to design and synthesize a library of PL-5ASA conjugates with different linkers between the PL and the drug moiety; 2) to evaluate the PLA2-mediated activation and the intestinal permeability of the prodrugs (enabling the design/synthesis of optimal conjugates), thereby to identify the most promising prodrugs; and 3) to develop an IBD rat model, to quantify PLA2 expression/activity in diseased vs. control animals, and to evaluate the leading PL-5ASA conjugates for in-vivo drug targeting, pharmacokinetics and pharmacodynamics vis-à-vis other 5ASA products. The findings will significantly improve drug therapy in IBD patients, enabling higher efficacy and lower toxicity profiles.

Keywords: inflammatory bowel diseases,drug targeting,prodrug approach,phospholipid-drug conjugate,phospholipase a2 overexpression
Effect of controlled hyaluronan synthesis on the stemness of aged mesenchymal stem cells (HYALSTEMAGE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Austria,Austria
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-04-01
End date: 2014-03-31
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 2
Project status: CLOSED

Hyaluronan (HA), a linear polysaccharide in the extracellular matrix (ECM) of higher animals is a key player in tissue remodelling. Mesenchymal stem cells (MSC) exhibit multipotential differentiation capacities and are therefore of high clinical importance. Novel cell therapeutic approaches based on the differentiation and regeneration potential of MSC have been developed and successfully applied in numerous clinical studies. The stemness of MSC is described by their ability to form colonies and to differentiate into mesenchymal tissues. Prior clinical applications MSC are propagated in vitro to increase the number of multipotential cells and thereby maximising the chance of a therapeutic success. So far however, cell expansion can only be achieved at the expense of MSC stemness and diminished multipotentiality. The aim of this project is to unravel forces that drive these detrimental processes during MSC propagation. In particular, the proposed work addresses alterations in HA content of the extracellular matrix during cultivation. Depending on the HA length, cell proliferation and differentiation is either inhibited or promoted. High molecular weight HA restrains cell division whereas short HA fragments are shown mitotic. Hyaluronan synthases (HAS) generate the unbranched biopolymer at the plasma membrane. HAS are differentially expressed when comparing young against aged cells. In particular HAS3 was found to be upregulated in senescent fibroblasts and MSC. The goal of this project is to investigate the role of HAS3 during MSC ageing and to rate whether elevated levels of HA production advances the progression of cell senescence. We hypothesise that controlling the HA content in the pericellular space may not only allow to decelerate the progression of MSC senescence but also to yield sustained fitness of expanded MSC for therapeutic applications.

Keywords: mesenchymal stem cells,hyaluronan,hyaluronan synthase,ageing,senescence,cell therapy,extracellular matrix
Angiogenesis Research to Improve Therapies for Vascular Malformations (CVM THERAPY)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Israel
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-03-15
End date: 2015-03-14
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Congenital Vascular Malformations (CVM) are a group of diseases characterized by an inborn, localized defects of vascular morphogenesis. Occurring mainly on the face or other highly visible part of the body, the presence of CVM can cause emotional and social problems. Moreover, some malformations are painful or even life-endangering. Current treatments do not achieve optimal or long-lasting results. Thus, there is a pressing need for therapies that are more effective for these disfiguring lesions. Currently, the cellular components of the CVM have not been isolated and analyzed, and there is no animal model for most CVM. One attractive treatment strategy is to induce transdifferentiation of the endothelial cells (ECs) of the lesion. Transdifferentiation is the reprogramming of one specialized cell type into another, without reversion to pluripotent cells. The goal of my research is to isolate and characterize the EC, the major cellular component of the vascular malformations in order to develop targeted therapy for these lesions. EC and pericytes will be isolated from CVM tissues. We will perform extensive mutational analysis and epigenetic profiling of these primary cells in order to identify any abnormalities in their developmental path. Also, using novel techniques derived from the stem cell field, I will aim at inducing transdifferentiation of the l EC by forced expression of transcription factor pools. My hypothesis is that reprogramming the EC lining the vasculature of the lesion to a mesenchymal phenotype will lead to obstruction of these vessels and cessation of blood flow, resulting in significant improvement. Importantly, insights gained from this research will have wide implications for the vascular biology field. Thus, this project is novel and innovative. Having both extensive research experience with the study of angiogenesis and clinical expertise in Dermatology, I’m well-suited for the conduction of this project.

Keywords: health sciences,congenital vascular malformations,angiogenesis,endothelial cells,transdifferentiation,epigenetics
Correlative Super Resolution and Real-Time Imaging of Herpes Virus Infection (CSRR)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-03-01
End date: 2015-02-28
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Fluorescence imaging is a powerful technique that has transformed our understanding of biology. Recently, a number of techniques have been developed that overcome one of the fundamental limitations of fluorescence imaging, namely the diffraction limit. With these techniques, it is now possible to resolve sub-cellular architecture in multiple colors and 3D with unprecedented detail. However, the main limitation of these techniques has been the slow acquisition times making it difficult to study dynamic processes. Since biological samples are inherently highly dynamic, this limitation is a major hurdle that needs to be overcome. I will develop a correlative fluorescence imaging technique that combines the capabilities of super resolution and real-time imaging. With this correlative technique it will be possible to observe the dynamics of a biological sample in real-time and subsequently “freeze” the dynamics (by fixation or low temperature) at a time of interest to obtain a super resolution image. The dynamics can therefore be correlated with ultrastructural information, combining the capabilities of real-time and super resolution imaging. I will apply this correlative imaging technique to study infection mechanism of Herpes Simplex Virus (HSV). HSV is a medically important virus that infects neurons and epithelial cells. Besides the health hazards that it poses, HSV also has important implications in gene therapy. However, the details of HSV infection mechanism remain poorly understood. Since HSV infection involves dynamic interactions between virus particles and sub-cellular components, both of which are tens of nanometers in length scale, this is an ideal model system in which the correlative super resolution and real-time imaging technique will lead to important insights that were previously unattainable.

Keywords: biophysical techniques,cell biology,virology,microscopy,nanobiotechnology
FISCAL POLICY AND INFORMAL ECONOMY OVER THE BUSINESS CYCLE (FISINF)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Türkiye
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-03-01
End date: 2015-02-28
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The proposed project aims to understand whether and how informal sector affects behavior of fiscal policy over the business cycle and then develop an economic model using the state of the art techniques of dynamic macroeconomics that incorporates fiscal policy and informal economy. This model will be used to analyze various effects of the presence of an informal sector in European countries, specifically how it affects the cyclicality of fiscal policy and thereby economic growth and aggregate productivity over the business cycle.The proposed project is original and innovative in two major dimensions: (1) methodologically, it will advance the literature on cyclicality of fiscal policy and informal economy (2) the developed model will be used to analyze important policy issues for Europe that are not discussed at length previously.

Keywords: macroeconomics,economic policy,cyclical economics
HUMAN INDUCED PLURIPOTENT STEM CELLS AS A MODEL TO STUDY METABOLIC INHERITED LIVER DISEASES (IPSMILD)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-12-01
End date: 2014-11-30
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

Familial hypercholesterolemia type IIa (FH) is a life-threatening disease caused by mutations on the Low Density Lipoprotein Receptor (LDLR). While drug treatments reduce the level of circulating cholesterol in heterozygote patients (1:500) with variable efficiency, homozygote patients (1:106) can only be treated by bimonthly apheresis, an invasive procedure. Hepatocytes are the only cells capable to internalize and degrade cholesterol. We previously shown that we were able to generated iPS from normal human fibroblasts and differentiated them into hepatocyte-like cells. Our aim is to develop preclinical tools and models to study human monogenic liver metabolic diseases and evaluate the ex vivo gene/cell therapy approaches. Our study will be focused on patient specific model for FH. In addition to reproducing the pathology in vitro with hepatocyte-like cells-derived from heterozygote and homozygote FH patients, this model will allow us to study the impact of LDLR mutations on cholesterol homeostasis in a human context. At a more long-term, FH-derived hepatocytes should represent alternative tools for drug screening in an actual current context in which there are no cellular models displaying features of hepatocytes. They will enable testing the efficacy of new drugs on cholesterol pathway and their effects on the specific disease-related hepatocyte phenotype (cell differentiation and proliferation). Finally, this model will provide a tool to evaluate autologous gene/cell therapy with iPS-derived hepatocyte-like cells.

Keywords: natural sciences
Ultrafast Charge Transfer in ion-atom collision investigated by Molecular Quantum Dynamics Methods (DYNAMICOL)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Poland
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-03-01
End date: 2013-02-28
Duration (months): 24.0
Total project cost (EUR): 30000.0
EU funding (EUR): 30000.0
Participants: 1
Project status: CLOSED

The aim of the proposed project is to complete, maximize and enhance the scientific and management competencies gained by the applicant during the previous MC Fellowship, which she performed in Germany. The experience and complementary skills gained during the Fellowship are crucial for establishing herself as an independent scientist in the field of the ultrafast dynamics. The financial contribution of the European Reintegration Grant will support a young researcher with her effort to set up her own research group in Poland.The DYNAMICOL project is devoted to the study of the dynamics of charge transfer (CT) processes taking place in a collision in the femto and attosecond time scales. The development of the ultrashort pulses produced by free-electron lasers and high harmonic generation has opened up the way to a new chemistry showing enormous possibility to observe the nuclear and electron motion in realm time. However, the dynamics of CT in the eV range of energy has been only scarcely investigated. DYNAMICOL aims at analyzing the mechanism of CT during an ion-atom collisions. Novel time-dependent wave packet propagation methods developed by the applicant to follow the attosecond nuclear motion involved in the collision at low energies will be applied. The methodology will be applied to the interactions between carbon ions, Cq+ (q=2,3,4,6), with H/He atoms. Firstly, to study the molecular structure of the systems, detailed knowledge of the potentials energies and non-adiabatic couplings between the states involved in the process will be obtained by using high level ab initio methods. Secondly, the dynamics of the process in ultrafast domain will be studied by the nuclear wave packet propagation methods. The simulations will be performed, as a first step in 1D, and second, in 2D. Combining these two possibilities, we will obtain anisotropic features of the global 3D collision process at low-energies, directly comparable with experiments.

Keywords: charge transfer,ultrafast dynamics,ab initio quantum chemistry methods,time-dependent electronic density,ion-atom collisions
Psoriatic Arthrtis and Coronary Artery Disease (PACAD)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Iceland
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-12-01
End date: 2015-06-30
Duration (months): 43.0
Total project cost (EUR): 89583.33
EU funding (EUR): 89583.33
Participants: 1
Project status: CLOSED

Background: Psoriatic arthritis is a multi-system auto-immune disease that affects approximately 0.15% of European populations. It can result in lost productivity and a decreased quality of life. The skin disease psoriasis is associated with cardiovascular disease. This is also true for rheumatoid arthritis. Initial data suggest an association between psoriatic arthritis and heart disease, but no population based studies exist. We propose a multi-disciplinary study combining advanced information technology and a collaboration between experts in cardiology and rheumatology. The proposed study is population based and addresses an important clinical question. Objective: To confirm and quantify the association between psoriatic arthritis and cardiovascular disease in the general population. Methods: Detailed population level data are available from the Icelandic Heart Association’s registry of every case of myocardial infarction occurring in the Icelandic population since 1981. We have previously compiled a list of all known cases of psoriatic arthritis in Iceland and propose linking this list to the heart disease registry. We will use statistical techniques including longitudinal data analysis to assess the risk of developing heart disease and cancer. To address confounding we will use two complimentary methods to compare the cardiovascular risk factor profiles of psoriatic arthritis patients to the general population. Benefits: The proposed project will improve the understanding of health risks associated with psoriatic arthritis. These risks can be taken into account when caring for these patients. Specifically, lifestyle modification and targeted screening can improve the survival and quality of life of cardiovascular patients. In addition to the scientific goals, this project will facilitate the reintegration of the applicant into the European and Icelandic research community, while bringing new research techniques and knowledge to the host institution.

Keywords: health sciences,psoriatic arthritis,myocardial infarction,cardiology,outcomes,health,population,epidemiology,public health,morbidity,mortality
Organizing the conference Week of Innovative Regions 2011 (WIRE2011)

Framework: FP7 — Capacities
Programme: Regions of Knowledge
Destination: Regions of Knowledge
Action type: Coordination and support actions
Countries involved: Hungary
Call:  (FP7-Adhoc-2007-13, 2007)
Start date: 2010-09-11
End date: 2012-02-10
Duration (months): 17.0
Total project cost (EUR): 442011.6
EU funding (EUR): 400000.0
Participants: 1
Project status: CLOSED

WIRE 2011 conference will bring together stakeholders from regional, national and European level research organizations, academia, and industry. WIRE 2011 and the preparation for the conference intends to gather reflections on the Europe 2020 strategy from the different institutional partners. Based on the three pillars of clusters, research and innovation policy, and research infrastructure, users’ oriented public approach should be developed during the preparation of the WIRE 2011. The conference could be a discussion forum where all stakeholders could present and discuss their specific ideas in order to create a regional framework for the future regional innovation concept. Based on the WIRE 2011 debate, the Debrecen Declaration will involve the main findings of the conference, and give an input for the Competitiveness Council meeting under the Polish Presidency.

Keywords: conference on cluster and research infrastucture cluster policy,esfri
The Moment of Truth for WIMP Dark Matter (WIMPS KAIROS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Fundamental constituents of matter
Countries involved: Netherlands
Call:  (ERC-2011-StG_20101014, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1248120.0
EU funding (EUR): 1248120.0
Participants: 1
Project status: CLOSED

Identifying Dark Matter is a top priority in Particle Physics and Cosmology. Among Dark Matter candidates, WIMPs (weakly interacting massive particles) play a special role, since they naturally arise from well motivated extensions of the standard model of particle physics. As I have argued in a recent \textsl{Nature} paper, with the advent of the Large Hadron Collider at CERN, and of a new generation of astroparticle experiments, the moment of truth has come for WIMPs, for we will either discover them in the next 5 to 10 years, or we will inevitably witness the decline of the WIMP paradigm. My collaborators and I have actually been preparing for this crucial moment for Dark Matter searches by setting up sophisticated statistical tools, strong connections with experimental collaborations, and an extensive expertise in theoretical models. We are now ready to perform the most complete analysis of Dark Matter data (from direct, indirect and accelerator searches, including all astrophysical uncertainties) in the framework of the most promising BSM (Beyond the Standard Model) theories, including Supersymmetry and Universal Extra Dimensions. Backed from a well established network of international collaborators, this project aims at becoming part of the theoretical backbone of astroparticle activities in Europe, and to exploit the data that will become available from the LHC at CERN, as well as from several infrastructures included in the ESFRI and ASPERA roadmaps, such as underground Dark Matter detectors and Neutrinos and Cherenkov Telescopes. No matter what the experimental results are, the impact on our understanding of the Universe will be dramatic, for we will either severely constrain possible extensions of the Standard Model, and push them to unnatural territory, or we will finally obtain incontrovertible for Dark Matter, therefore opening a new era in Particle Physics and Cosmology.

Keywords: astroparticle physics,wimps,dark matter searches