Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Targeting the Notch Protease Interface (NOTCH PROTEOLYSIS)

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: Netherlands,Netherlands
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2014-02-28
Duration (months): 66.0
Total project cost (EUR): 1200000.0
EU funding (EUR): 1200000.0
Participants: 2
Project status: CLOSED

NOTCH signaling is a highly conserved short-range signaling pathway involved in virtually every aspect of embryonic development and controls homeostatic self-renewal in many adult tissues. Germ line mutations in the NOTCH pathway cause several hereditary diseases, and somatic mutations are found in cancer. NOTCH pathway activity is governed by ligand induced proteolytic cleavage of the receptor in the extracellular domain by a metalloprotease. This cleavage is required for the consecutive transmembrane cleavage by the γ-secretase complex leading to the release of the intracellular domain that mediates target gene activation. The precise mechanism that confers ligand regulated NOTCH proteolysis is unresolved but involves a ligand-induced conformational change. Virtually nothing is known on how conformational changes render the NOTCH receptor susceptible to proteolysis and which proteases are involved. Human cancer prone NOTCH1 receptor mutations are characterized by increased metalloprotease dependent cleavage and signaling activity. Here I hypothesize that these oncogenic mutations lead to exposure of buried scissile bonds that facilitate proteolysis. Since metalloprotease cleavage of NOTCH receptors is the regulatory event in NOTCH cascade activation, inhibition of this protease activity may find therapeutic application in diseases with deregulated NOTCH signaling such as cancer. Novel technologies and reagents are needed to gain further insight into the NOTCH-protease interface to accelerate drug target discovery and validate their use in pre-clinical models for cancer where deregulated protease activity plays crucial roles in disease progression.

Keywords: metalloprotease,cancer biology,non-invasive imaging,activity based protein profiling,loss of function,proteomics,small molecules,mouse models,antibodies
Non-classical interacting random walks (NCIRW)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Mathematical foundations
Countries involved: Germany
Call:  (ERC-2007-StG, 2007)
Start date: 2008-10-01
End date: 2014-09-30
Duration (months): 72.0
Total project cost (EUR): 500000.0
EU funding (EUR): 500000.0
Participants: 1
Project status: CLOSED

The proposed project deals with various topics in the area of random walks (RWs) which interact with their own history and/or a possibly non-homogeneous, random environment. Such models arise from physics and other natural sciences as simplified models of complex phenomena and have recently attracted a lot of attention. They include: (a) Self-interacting RWs, i.e. RWs with memory, for example excited RWs, self-avoiding RWs, and RWs arising from two dimensional statistical mechanics models like Lorentz lattice gas models. (b) RWs in random media, for example RWs in random environments (RWRE), RWs on percolation clusters, and RWs in random potentials. Some of the problems to be considered concern recurrence and transience properties, laws of large numbers, ballistic versus sub-ballistic behavior, zero-one laws, scaling properties, other asymptotic properties, the relation between quenched and annealed behavior and monotonicity properties.

Keywords: self-interacting random walks,random walks in random media
Combinatorial methods, from enumerative topology to random discrete structures and compact data representations. (EXPLOREMAPS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Mathematical foundations
Countries involved: France
Call:  (ERC-2007-StG, 2007)
Start date: 2008-07-01
End date: 2013-06-30
Duration (months): 60.0
Total project cost (EUR): 750000.0
EU funding (EUR): 750000.0
Participants: 1
Project status: CLOSED

Our aim is to built on recent combinatorial and algorithmic progress to attack a series of deeply connected problems that have independantly surfaced in enumerative topology, statistical physics, and data compression. The relation between these problems lies in the notion of "combinatorial map", the natural discrete mathematical abstraction of objects with a 2-dimensional structures (like geographical maps, computer graphics' meshes, or 2d manifolds). A whole new set of properties of these maps has been uncovered in the last few years under the impulsion of the principal investigator. Rougly speaking, we have shown that classical graph exploration algorithms, when correctly applied to maps, lead to remarkable decompositions of the underlying surfaces. Our methods resort to algorithmic and enumerative combinatorics. In statistical physics, these decompositions offer an approach to the intrinsec geometry of discrete 2d quantum gravity: our method is here the first to outperform the celebrated "topological expansion of matrix integrals" of Brezin-Itzykson-Parisi-Zuber. Exploring its implications for the continuum limit of these random geometries is our great challenge now. From a computational geometry perspective, our approach yields the first encoding schemes with asymptotically optimal garanteed compression rates for the connectivity of triangular or polygonal meshes. These schemes improve on a long series of heuristically efficient but non optimal algorithms, and open the way to optimally compact data structures. Finally we have deep indications that the properties we have uncovered extend to the realm of ramified coverings of the sphere. Intriguing computations on the fundamental Hurwitz's numbers have been obtained using the ELSV formula, famous for its use by Okounkov et al. to rederive Kontsevich's model. We believe that further combinatorial progress here could allow to bypass the formula and obtaine an elementary explanation of these results.

Keywords: enumeration,enumerative topology,random discrete structures,design and analysis of algorithms,data structures
Deeply Supercooled Liquid Water (SULIWA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Condensed matter physics
Countries involved: Austria
Call:  (ERC-2007-StG, 2007)
Start date: 2008-08-01
End date: 2013-07-31
Duration (months): 60.0
Total project cost (EUR): 1389238.0
EU funding (EUR): 1389238.0
Participants: 1
Project status: CLOSED

Water is ubiquitous and so an understanding of water’s anomalous liquid state is crucial for such diverse fields as protein biochemistry, meteorology or astrophysics. A postulated first order phase transition between two distinct one-component liquids at low temperatures is believed to be the key to many riddles in contemporary science: a “fragile” liquid of high density and a “strong” liquid of low density. At higher temperatures the phase boundary might end in a speculative second critical point in supercooled water. Unfortunately it has not been possible so far to support/falsify these hypotheses with direct experiments because of fast crystallization of the liquid(s) in the relevant portion of the phase diagram, which is called "no man's land". Therefore, experiments to test the hypothesis were previously done in the non-crystalline, solid state (“amorphous water”) at temperatures well below the "no man's land". More than 20 years ago liquid-like relaxation was measured on heating glassy water at 1 bar to 136 - 150 K, i.e., to temperatures slightly below crystallization, which is still discussed controversially. Recently we managed to observe liquid-like properties on heating high density amorphous ice (HDA) under isobaric conditions at pressures up to 1 GPa above its glass-liquid transition at a temperature slightly below the "no man's land" without observing significant crystallization. These findings open the exciting possibility to characterize (e.g., by dilatometry, thermal analysis and dielectric spectroscopy) deeply supercooled liquid water both at ambient and high pressure conditions and to check if water indeed shows a first order liquid-liquid phase transition between two distinct liquids. This will unravel the question how many liquids and how many corresponding amorphous states there are in water, and if VHDA discovered by us in 2001 shows a polyamorphic transition to HDA, or if it is simply annealed HDA.

Keywords: glass-liquid transition
Intraspecific Diversity and Adaptability of Fucus vesiculosus at range limits (IDA)

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: Germany
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2007-10-01
End date: 2012-03-09
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 2
Project status: CLOSED

Intraspecific genetic diversity is the ‘raw material’ that allows species to adjust to a changing world. For predictions of the effects of Global Change, it is crucial to know if low genetic diversity is a result of local adaptation (i.e. if a species has experienced strong selection), or if other processes are responsible. The Baltic Sea is an extreme marine environment and its extreme temperature and salinity gradients are likely to be strong selective forces. A recent review revealed that for many Baltic Sea species, intraspecific genetic diversity was lower than in the North Sea or Atlantic. It remains unknown, however, if genetic diversity declines with increases in environmental stress and/or if marginal populations (assumed to experience highest selection) show the lowest genetic diversity. The proposed research focuses on the selective forces behind diversity loss in the bladder-wrack, Fucus vesiculosus L., a canopy forming keystone species in the Baltic Sea. On the other hand, ecological consequences (i.e. population adaptability) of a changed diversity at distributional edges will be examined. We will study changes in genetic diversity associated with various stresses by first examining the population genetic diversity and structure of F. vesiculosus along the environmental gradients in the Baltic Sea, focusing on latitudinal edges, edges within estuaries and edges on slopes. Secondly, we will conduct laboratory experiments that challenge germlings of F. vesiculosus with different stresses (temperature, salinity, light and nutrient levels). The fitness of different genotypes will be examined under different environments and interactions between factors will be tested. Additionally, genetic diversity of germling populations will be varied to test whether more diverse populations are more tolerant to stress. Finally, in collaboration with other laboratories we will search for genetic polymorphisms that are directly linked to genes with putative function.

Keywords: microsatellites,genetic diversity,range limit,selection experiment
Exploring mechanism in chemical biology by high-throughput approaches (CHEMBIOMECH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physical and Analytical Chemical sciences
Countries involved: United Kingdom
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2013-08-31
Duration (months): 60.0
Total project cost (EUR): 563848.0
EU funding (EUR): 563848.0
Participants: 1
Project status: CLOSED

In the biomedical sciences, where endless combinatorial diversity of genes, proteins and synthetic molecules is involved, miniaturisation has not simply allowed an increase in the speed at which experiment can be performed: it has given birth to new areas such as combinatorial chemistry and biology, proteomics, genomics, and more recently, systems and synthetic biology. In all these areas, the synthesis, assay and analysis of large molecular ensembles has become the essence of experimental progress. However, it is the systematic analysis of the enormous amounts of data generated that will ultimately lead to an understanding of fundamental chemical and biological problems. This proposal deals with approaches in which libraries of molecules are employed to give such mechanistic insight – into how enzyme catalysis is brought about in proteins and polymeric enzyme models and into the molecular recognition and cell biology of drug delivery reagents. In each case considerable technical challenges are involved in the way diversity is brought about and probed: ranging from either using the tools of synthetic chemistry to using gene repertoires in emulsion microdroplet reactors with femtolitre volumes, handled in microfluidic devices.

Keywords: directed evolution,display technologies,genotype-phenotype linkage,microfluidics,enzyme mechanism,enzyme models,physical-organic chemistry,organic mechanism,protein engineering
Advancing Understanding of Carbon Cycling and Coloured Dissolved Organic Matter Dynamics in European Wetlands & Coastal Ecosystems through integration of observations and novel modelling approaches (ECODOM)

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: Greece
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2008-05-01
End date: 2012-04-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

This proposal aims at facilitating an efficient and lasting re-integration of Dr Maria Tzortziou in the Hellenic Center for Marine Research (HCMR). The main goal is to initiate a competitive and interdisciplinary research program at HCMR that will advance our understanding of the role that wetlands and tidal marshes play in dissolved organic matter (DOM) dynamics, carbon cycling, photochemistry, biogeochemistry, and water quality changes in coastal margin ecosystems. Specific objectives of the research initiated with EcoDOM include: (i) Characterize landscape-scale variation in the quantity and quality of the dissolved organic compounds exported from different wetlands and coastal tidal marshes in SE Europe, and understand implications of such variation for estuarine biogeochemistry, ecosystem productivity, and water optics. (ii) Develop novel and improved modelling approaches for describing and predicting effects of photochemical processes on DOM quality and degradation. Accurate quantitative description of these effects is prerequisite for improving the accuracy of more general biogeochemical/ecological models of carbon cycling. (iii) Apply a novel radiative transfer model to examine the effects of wetland DOM inputs on underwater light fields. (iv) Link the proposed work to remote sensing applications by developing bio-optical relationships between remotely sensed quantities, DOM optical properties and biogeochemical variables in coastal waters. EcoDOM research is highly relevant to the European Union policy making and research initiatives for increased understanding and modelling of climate-related biogeochemical cycles in European wetland ecosystems and sustainable management of EU’s coastal natural resources. The HCMR Institute of Inland Waters is committed to absorb the research initiated in the proposed project by offering job stability through long-term research scientist appointments to Dr Tzortziou with the conclusion of the project.

Keywords: carbon cycle (climate change),wetland ecosystems (climate change),coastal zone ecosystems (climate change),biochemical and hydrological cycles,applied optics,remote sensing,algorithms
Trancriptional control of dendritic arbors morphology in pathogeny and therapy of neuropsychiatric diseases. (PSYCHIAPROTEGENOMIC)

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-2007-4-3-IRG, 2007)
Start date: 2007-09-03
End date: 2012-02-02
Duration (months): 53.0
Total project cost (EUR): 110416.67
EU funding (EUR): 110416.67
Participants: 1
Project status: CLOSED

Neuropsychiatric disorders affect 25% of the population sometime during their life. Aberrant dendritic arbors appear in mental disorders. Although the psychopathological mechanisms are not completely understood, it has been suggested that changes in gene expression contribute to the development and therapy. Several evidences, including the applicant own studies, suggest that misregulation of Sp4 transcription factor could be involved in the pathogenesis and therapy of affective disorders by controlling dendritic patterning. The applicant will explore the possibility that Sp4 and other transcriptional regulators might be altered in postmortem human brains of patients with mental disorders. This research pretends also to investigate the capability to regulate dendritic development by altered novel factors and psychotropic treatment. This project we will test the hypothesis that mood stabilizer and antipsychotic drug leads to a physiological dendritic patterning, in part, through the stabilization/activation of Sp4 transcription factor which leads to changes in expression of genes important for the pathogenesis and therapy of neuropsichiatric disorders. To address that hypothesis (a) we will study whether the levels of Sp4 transcription factor protein or other factors are altered in postmortem brain tissue from patients with schizophrenia or affective disorders. (b) We will perform a novel quantitative proteomic approach (SILAC) and gene expression arrays in postmortem brain of neuropsychiatric patients and whether the new hits module dendritic patterning. (c) And also, we will study the effect of mood stabilizers and antipsychotics on dendritic morphology by Sp4-dependent mechanism. These studies will give a new insight in the transcriptional programs controlled by lithium which may regulate dendritic morphology and, will provide the regulation of Sp4 u others factors as a possible mechanism involved in the pathogenesis and therapy of neuropsychiatric disorders.
An investigation of the middle atmosphere response to impulsive ozone perturbations (ARIA)

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: Italy
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2007-10-01
End date: 2010-09-30
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

We propose to investigate the impact of impulsive ozone perturbations on the middle atmosphere. Impulsive perturbation experiments of increasing complexity will be performed on a stratosphere-mesosphere model and the radiative and dynamical response systematically investigated under a range of conditions. Satellite observations of transient ozone changes retrieved with a new 2-dimensional algorithm will be compared to reanalysis data and model results. The comparison will help identifying sources of atmospheric variability and estimating the characteristics of extreme responses, aiding current global circulation models and our understanding of observed climate change. The project aims at developing a common strategy for analysing and interpreting model results, reanalysis data and short term satellite observations, identifying meaningful diagnostics to be used in dynamically controlled regions of the atmosphere where large non-linear responses can arise. An interdisciplinary approach is needed and it is possible coupling the expertise of the candidate on model perturbation experiments and transient phenomena developed during the previous EU Research Training Network, with the state-of-the-art MIPAS/ENVISAT retrieval capabilities and chemistry knowledge of the host institute. The continuation and extension of close collaborations developed with other members of the previous network will guarantee a continuous interaction with experts of middle atmospheric modelling, stratosphere-troposphere coupling, ion-chemistry modelling and transient luminous events.

Keywords: middle atmosphere ozone perturbations variability modelling mipas satellite
Global Optimization Methods in Computer Vision, Pattern Recognition and Medical Imaging (GLOBALVISION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Materials and Synthesis
Countries involved: Sweden
Call:  (ERC-2007-StG, 2007)
Start date: 2008-07-01
End date: 2013-06-30
Duration (months): 60.0
Total project cost (EUR): 1440000.0
EU funding (EUR): 1440000.0
Participants: 1
Project status: CLOSED

Computer vision concerns itself with understanding the real world through the analysis of images. Typical problems are object recognition, medical image segmentation, geometric reconstruction problems and navigation of autonomous vehicles. Such problems often lead to complicated optimization problems with a mixture of discrete and continuous variables, or even infinite dimensional variables in terms of curves and surfaces. Today, state-of-the-art in solving these problems generally relies on heuristic methods that generate only local optima of various qualities. During the last few years, work by the applicant, co-workers, and others has opened new possibilities. This research project builds on this. We will in this project focus on developing new global optimization methods for computing high-quality solutions for a broad class of problems. A guiding principle will be to relax the original, complicated problem to an approximate, simpler one to which globally optimal solutions can more easily be computed. Technically, this relaxed problem often is convex. A crucial point in this approach is to estimate the quality of the exact solution of the approximate problem compared to the (unknown) global optimum of the original problem. Preliminary results have been well received by the research community and we now wish to extend this work to more difficult and more general problem settings, resulting in thorough re-examination of algorithms used widely in different and trans-disciplinary fields. This project is to be considered as a basic research project with relevance to industry. The expected outcome is new knowledge spread to a wide community through scientific papers published at international journals and conferences as well as publicly available software.

Keywords: computer vision,object recognition,inverse problems,optimization,reconstruction problems,image analysis