Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Protein assembly: From the molecular scale to the mesoscale with super-resolution imaging (PALMASSEMBLY)

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: Switzerland
Call:  (ERC-2009-StG, 2009)
Start date: 2009-12-01
End date: 2015-11-30
Duration (months): 72.0
Total project cost (EUR): 1542518.0
EU funding (EUR): 1542518.0
Participants: 1
Project status: CLOSED

Cellular responses to external signals begin at the plasma membrane, where the dynamic assembly of receptors can regulate cellular activity. Membrane-enveloped viruses, including the human immunodeficiency virus (HIV) also assemble at the plasma membrane, exploiting mechanisms evolved for cellular trafficking. However, our physical paradigm for how proteins form mesoscale assemblies is far from complete. While the organization and dynamics of membrane proteins are heterogeneous, commonly used fluorescence-based measurements lack information at the molecular scale. In contrast, single molecule measurements limited to looking at only a few molecules in a given cell lack ensemble information. Thus, the study of protein assembly has been limited by a lack of spatially resolved, dynamic information on ensembles of molecules. We will use super-resolution fluorescence imaging techniques combined with live cell imaging and single molecule tracking to determine how the dynamics of protein assembly are coordinated. The long-term goal of my research is to use quantitative fluorescence methods to identify the physical mechanisms for protein transport and organization in cells. The objective of this proposal is to establish quantitative models of protein assembly in two specific biological systems which were selected for the distinct characteristics of their assembly, and their relevance to human health. This will test the central hypothesis that molecular assembly is enhanced by the organization of the plasma membrane in the form of cytoskeletal elements and protein-lipid platforms. This interdisciplinary research will provide an experimental foundation for a statistical description of the cell, whose behaviour is embedded in protein organization and dynamics.

Keywords: super-resolution imaging,protein assembly,protein transport,anomalous diffusion
Temperature perception and signal transduction in plants (TEMPEST)

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: United Kingdom,United Kingdom
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2015-02-28
Duration (months): 64.0
Total project cost (EUR): 1699508.4
EU funding (EUR): 1699508.4
Participants: 2
Project status: CLOSED

We seek to understand how plants perceive temperature. Being sessile organisms, plants are acutely sensitive to changes in ambient temperature, and are able to detect and respond to a change of as little as one degree Celsius. To directly address how plants sense temperature change, we have devised and implemented a novel forward genetic screen for mutants impaired in their ability to detect temperature correctly. Initial results demonstrate an interesting connection between chromatin structure and temperature sensing, which we are able to show is conserved within eukaryotes. Understanding the molecular basis of temperature perception is of interest from both a fundamental scientific perspective as well as having implications for understanding how plants (which comprise more than 1.25 trillion tonnes of biomass) will respond to climate change. The distribution and flowering time of wild plants has already been measurably altered by climate change, and this will become more dramatic under projected changes. Knowing the mechanisms of temperature perception will facilitate crop-breeding programs as well as provide important knowledge for predicting future effects of climate change. To this end, we propose a multi-disciplinary program exploiting two powerful model systems, Arabidopsis thaliana and Brachypodium distachyon, to address 5 key questions: 1. What is the molecular basis for temperature perception? 2. How is the temperature transcriptome coordinately regulated? 3. How are the flowering time pathways regulated by temperature? 4. How do plants adapt to different climates?

Keywords: arabidopsis thaliana,brachypodium distachyon,temperature perception,flowering time
Novel tools for real time monitoring and quantification of protein aggregation in Parkinson s disease and related neurodegenerative disorders (NOVEL TOOLS IN PD)

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: Switzerland
Call:  (ERC-2009-StG, 2009)
Start date: 2009-12-01
End date: 2014-11-30
Duration (months): 60.0
Total project cost (EUR): 1495400.0
EU funding (EUR): 1495400.0
Participants: 1
Project status: CLOSED

To understand the molecular basis of any biological process, it is critical that one is not only able to visualize and monitor molecular events that underlie this process, but also to possess the tools to manipulate these events in a spatial and temporal fashion both in and out of the cell. The overall objective of this proposal is to apply chemical biology approaches to allow real time monitoring of protein aggregation and to dissect the role of specific disease-associated post-translational modifications, phosphorylation, nitration, and truncation on the structure, aggregation, and biochemical properties of monomeric a-syn in health and disease. To achieve these goals, we plan to use a combination of organic chemistry, molecular biology, proteomics, protein engineering, and semisynthetic strategies to facilitate site-specific introduction of post-translational modifications that can be masked and activated in a controllable manner, both inside and outside living cells. Modified synthetic ±-syn will be introduced into primary neurons and cellular models of synucleinopathies and the consequences of masking or activating specific modifications will be assessed using biochemical, immunofluorescence, and live imaging techniques (Specific Aim 1). The absence of specific molecular probes that allow in vivo monitoring and quantitative measurement of toxic misfolded and aggregation intermediates represents a major impediment to understanding the relationship among protein misfolding, post-translational modification, protein aggregation, neurodegeneration, and cell death in PD and other neurodegenerative disorders. To address this challenge, we plan to develop and characterize novel antibodies that target different species along the amyloid formation pathway of ±-syn (Specific Aim 2).

Keywords: amyloid,truncation,phosphorylation,nitration,contrast agents,imaging,mri,phage display,antibodies
The role of protein-tyrosine phosphatases in breast development and cancer (PTPSBDC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Switzerland
Call:  (ERC-2009-StG, 2009)
Start date: 2010-02-01
End date: 2015-01-31
Duration (months): 60.0
Total project cost (EUR): 1571364.8
EU funding (EUR): 1571364.8
Participants: 2
Project status: CLOSED

Each year 1.1 million new cases of breast cancer will occur among women worldwide and 400,000 women will die from this disease. Although progress has been made in understanding breast tumor biology, most of the relevant molecules and pathways remain undefined. Their delineation is critical to a rational approach to breast cancer therapy. This proposal focuses on the role of the under-explored family of protein-tyrosine phosphatases (PTPs) in the normal and neoplastic breast. Virtually all cell signaling pathways are modulated by reversible protein tyrosine phosphorylation, which is regulated by two classes of enzymes: protein-tyrosine kinases (PTKs) and PTPs. Not surprisingly, tyrosine phosphorylation has an important role in breast development and cancer. Whereas the role of specific PTKs, like the HER2 receptor, in breast cancer is well studied, almost nothing is known about the function of specific PTPs in this disease. Our preliminary data suggest that PTP1B has an important role in breast differentiation and that both PTP1B and SHP2 play positive roles in breast cancer. The two predominant goals of this proposal are: First, to delineate the role of PTP1B and other PTPs in normal breast development and differentiation; second, to address the roles of PTP1B and other PTPs in the maintenance of breast cancer and metastasis and to assess their merits as drug targets. These studies not only use state-of-the-art ex vivo and in vivo models for studying breast pathophysiology, but also cross the boundaries between the developmental and cancer research fields and between basic science and clinical applications. Our research should ultimately lead to the rational design of targeted therapies that will improve the clinical management of patients with breast cancer.

Keywords: breast development breast cancer protein-tyrosine phosphatases
'Systems' study of cellular growth, shape and polarity (SYSGRO)

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
Call:  (ERC-2009-StG, 2009)
Start date: 2010-02-01
End date: 2016-01-31
Duration (months): 72.0
Total project cost (EUR): 1697400.0
EU funding (EUR): 1697400.0
Participants: 1
Project status: CLOSED

A major challenge of modern biology is to elucidate how cellular structure and function result from the systemic action of the genome and proteome. In this proposal, we describe an integrated approach combining high-content and quantitative microscopy, systematic gene knockouts, and computational/theoretical methods to carry out the most detailed systemic study of three key aspects of cell physiology: growth, shape and polarity. We will use the fission yeast Schizosaccharomyces pombe as experimental model organism. The haploid fission yeast with its relative genomic simplicity, genetic tractability, uniform size and shape, and well-characterized, conserved and simple growth and polarization machinery is ideal for this study. A better understanding of the systemic regulation of those processes is likely to contribute in the long run to the development of better strategies to fight cellular pathologies associated with many diseases, such as cancer.

Keywords: high-content,microscopy,image processing,cell growth,cell shape,cell polarity
Integrative structure and function study of the bacterial and human protein synthesis machinery. (TRANSLATIONMACHINERY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: France
Call:  (ERC-2009-StG, 2009)
Start date: 2009-12-01
End date: 2014-11-30
Duration (months): 60.0
Total project cost (EUR): 1690000.0
EU funding (EUR): 1690000.0
Participants: 1
Project status: CLOSED

The aim of the project is to understand key steps in the molecular mechanisms of protein synthesis across species. The structure and function of pro- and eukaryotic (including human) ribosomes, those cellular nano-machineries that catalyse the decoding of genes, will be studied through an integrative, interdisciplinary structural biology approach. Since in the cell the ribosome is regulated by transiently binding protein and RNA factors, we plan the reconstitution and structural investigation of ribosome complexes in functionally defined states with regulatory proteins and messenger RNAs (mRNA). Four work packages will form the basis of the investigation, (i) the role of mRNA structure in gene expression in pro- and eukaryotes, (ii) the mechanism of translation initiation in prokaryotes as important antibiotic targets, (iii) the high-resolution structure of the human ribosome, and (iv) the architecture of eukaryotic polysomes, the functional protein synthesis entities of living cells. The complexes will be studied using a comprehensive approach which will incorporate biochemistry, structural biology, biophysics and bio-informatics, with cryo-electron microscopy and X-ray crystallography forming the core. The dynamic aspects of the protein synthesis machinery such as structural and functional transitions will be investigated by separation of multiple states through advanced image processing procedures, molecular dynamics simulations and by exploring new developments in optical imaging. Collaborations with leading laboratories have been set up in order to create an efficient framework for which the host institute provides an outstanding infrastructure. The project will provide fundamental knowledge on the mechanism of gene expression regulation at the level of protein synthesis contributing in the long term to the development of new drugs.

Keywords: integrative structural biology,molecular machineries
Mechanisms of retrotransposition in humans and consequences on cancer genomic plasticity. (RETROGENOMICS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: France
Call:  (ERC-2009-StG, 2009)
Start date: 2010-01-01
End date: 2014-12-31
Duration (months): 60.0
Total project cost (EUR): 1874000.0
EU funding (EUR): 1874000.0
Participants: 1
Project status: CLOSED

Retrotransposons are a class of highly repetitive sequences, which are very abundant in the human genome. They disperse by an RNA-based copy-and-paste mechanism, called retrotransposition. This process can drive profound genome rearrangements. Although generally silent, they are expressed in germ cells, in the early embryo, and in embryonic stem cells, which occasionally results in genetic diseases. Retrotransposons are also massively re-expressed in the large majority of cancers, but the importance and consequences of retrotransposition in human tumors have been poorly studied. Somatic retrotransposition is difficult to track in human tissue due to the highly repetitive and dispersed nature of these elements. Thus the questions we wish to address in this research proposal are the following: (i) What cellular pathways control retrotransposon copy number? This will be achieved by combining functional genomics and proteomics approaches to identify positive and negative regulators of retrotransposition in humans. (ii) What are the molecular mechanisms of retrotransposons replication? To answer this question, we will develop a cell-free assay that will contain the complete retrotransposition machinery. (iii) How retrotransposons participate in the normal and pathological remodeling of the human genome? To this purpose we are currently developing innovative approaches to track retrotransposition events in clinical samples, especially in tumor samples. Since LINE-1 elements (L1) are the most active and autonomous retroelements in our genome, we focus, at the moment, our investigations on this family. Understanding how the activity of retrotransposons is controlled will impact our knowledge of the mechanisms that lead to new genetic diseases or to cancer progression. Since mobile genetic elements are becoming important tools in insertional mutagenesis or gene-transfer technologies in mammals, our work should also help to improve their use in mammalian functional genomics.

Keywords: transposable elements,retrotransposon,reverse transcriptase,ribonucleoprotein,genome plasticity
Support to the Chair and Vice-Chairs of the ERC Scientific Council 2009 (ERCSC-CHAIRS-SUP2009)

Framework: FP7 — Cooperation
Programme: General Activities
Destination: General Activities
Action type: Coordination and support actions
Countries involved: United Kingdom
Call:  (FP7-Adhoc-2007-13, 2007)
Start date: 2009-01-01
End date: 2010-02-28
Duration (months): 14.0
Total project cost (EUR): 296006.0
EU funding (EUR): 296006.0
Participants: 1
Project status: CLOSED

The proposed project aims to support the ScC Chair and Vice-Chairs in the efficient and timely achievement of the ScC objectives in 2009. It will support and assist Professor F.C. Kafatos (Chair of the ERC ScC), Dr. D. Esteve (Vice-Chair of the ERC ScC) and Professor H. Nowotny (Vice-Chair of the ERC ScC) in their diverse responsibilities which include the achievement of efficient and effective functioning of the ScC as a policy making body, its integrated operation together with the ERC’s Dedicated Implementation Structure (DIS), and effective interfacing with the scientific community, other funding agencies and the political institutions of the European Union and beyond. The project will provide, for a period of one year, local administrative, operational and advisory support, ranging from secretarial tasks to assistance in developing policy papers and outreach material and analyzing the results from the funding calls, related to the mission of the Chair and Vice-Chairs of the ERC ScC. The impact of the project will be to ensure an efficient and well-managed operation of the ERC ScC. By providing high-level local support for the EcC Chairman who is based at Imperial College London (UK), and the two Vice-Chairs who are based at Commissariat Energie Atomique (CEA) in Saclay (France) and Wiener Wissenschafts Forschungs und Technologiefonds (WWTF) in Vienna (Austria) respectively, the project will complement the activities of and allow efficient interfacing with the DIS. Overall, the project is expected to contribute significantly to the implementation of the Ideas specific programme. The proposed project will be a continuation and expansion of the ongoing project "ERCSC-CHAIR-SUP 2008—Support to the Chair of the ERC Scientific Council 2008" Project No. 225646.

Keywords: european research council,scientific council,chair,vice-chairs,support
Neural mechanisms of action learning and action selection: from intent to habit (NEUROHABIT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Portugal
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2014-10-31
Duration (months): 60.0
Total project cost (EUR): 1526304.0
EU funding (EUR): 1526304.0
Participants: 2
Project status: CLOSED

In every day life, we constantly have to select the appropriate actions to obtain specific outcomes. Actions can be selected based on their consequences, for example when we press an elevator button to get to the particular floor where we live. This goal-directed behaviour is crucial to face the ever-changing environment but demands an effortful control and monitoring of the response; one way to balance the need for flexibility and efficiency is through automatization of recurring decision processes as a habit. Habitual responses no longer need the evaluation of their consequences, and can be elicited by particular situations or stimuli, for example when we press the button for our home floor in a building that we are visiting for the first time. There is growing evidence that the neural circuits underlying intentional or goal-directed actions are different from those underlying habits; associative corticostriatal circuits have been implicated in goal-directed actions, and sensorimotor circuits in habit formation. Dopamine (DA) has been implicated in both voluntary actions and habits. However, DA neurons from the VTA and the SNc project to different cortical and striatal regions, and the specific role of VTA and SNc DA in goal-directed actions and habits has not been clarified. We propose to: 1) use cell-type and region specific genetic manipulations to test if phasic firing in VTA or SNc DA neurons is necessary for goal-directed actions or habits, respectively, 2) generate cell-type specific channelrodhopsin transgenic mice to test if phasic DA neuron firing in these areas is sufficient to produce goal-directed actions or habits, and 3) selectively manipulate striatal neurons modulated by VTA or SNc phasic DA to test if they are necessary for goal-directed actions or habits. The dissection of the molecular and circuit mechanisms underlying goal-directed and habitual responses will be critical to understand decision-making, and the origins of compulsive behaviour.

Keywords: striatum,goal-directed,decision-making,dopamine,channelrodhopsin,in vivo recordings
Technologies for the cost-effective Flood Protection of the Built Environment (FLOODPROBE)

Framework: FP7 — Cooperation
Programme: Environment (including Climate Change)
Destination: Environmental technologies
Action type: Collaborative project
Countries involved: Netherlands,United Kingdom,France,Norway,France,Spain,Poland,France,Czechia,Czechia,Netherlands
Call:  (FP7-ENV-2009-1, 2009)
Start date: 2009-11-01
End date: 2013-10-31
Duration (months): 48.0
Total project cost (EUR): 4636982.0
EU funding (EUR): 3498727.15
Participants: 15
Project status: CLOSED

The principal aim of FloodProBE is to provide cost-effective means for the flood protection and damage mitigation in urban areas. To this end, FloodProBE will develop, test and disseminate technologies, methods, concepts and tools for risk assessment and mitigation, focussing particularly on the adaptation of new and existing buildings (retrofitting) and on infrastructure networks. The three main elements addressed by FloodProBE are (a) the vulnerability of critical infrastructure and high-density value assets, being the main originators of direct and indirect flood damage, (b) the reliability of urban flood defences by improving understanding and assessment of failure processes that have proven to be critical in recent flood events and (c) construction technologies and concepts for flood-proofing buildings and infrastructure networks to increase the flood-resilience of the urban system as well as for retrofit and repair of flood defences in the most economic and cost beneficial manner. The afore-mentioned elements will be integrated into state-of-the-art flood risk management strategies and will be developed, tested and validated via pilot study sites. A wide range of stakeholders will be involved in the project from the outset through an Associate Partner programme and by an external Advisory Board. This involvement will provide guidance on the project programme to directly meet industry needs, whilst also facilitating international dissemination, supporting uptake and implementation of project deliverables. The primary impact of FloodProBE will be a significant increase in the cost-effectiveness (i.e. performance) of investments in newly developed and existing flood protection and flood resilience measures. This will be achieved by focusing the research on “risk hotspots”, i.e. weak links in flood defence system performance and vulnerable assets, that, if damaged, cause very large direct and indirect adverse consequences (e.g. infrastructure networks).

Keywords: flood protection technology,vulnerability analysis,flood defences,building flood resilience,assessment methods and tools,construction technologies and concepts,urban areas