Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Nuclear foundations of cellular potency (NUCLEARPOTENCY)

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-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2018-01-31
Duration (months): 72.0
Total project cost (EUR): 1496000.0
EU funding (EUR): 1496000.0
Participants: 2
Project status: CLOSED

A fundamental question in biology is to understand the mechanisms underlying cell plasticity. Such plasticity or potency is essential to form multiple cell types upon differentiation. In mammals, upon fertilization and fusion of the gametes –two highly differentiated cells- intense chromatin remodeling and epigenetic reprogramming, the reversion into an undifferentiated state, are essential to restore full developmental potency (totipotency). Subsequent development and differentiation are accompanied with progressive loss of plasticity. The transition between totipotency and the gradual loss of plasticity is thought to be regulated by yet-unknown epigenetic mechanisms. The embryonic chromatin displays unique features compared to differentiated cells, including the lack of ‘conventional’ heterochromatin. We hypothesise that the transition from a totipotent state to a differentiated one is regulated by changes in chromatin states, particularly by de novo acquisition of heterochromatin domains. This project is designed to reveal the nuclear foundations of totipotency by determining the molecular mechanisms underlying the establishment of heterochromatin and their functional role in maintaining totipotency using the mouse embryo as model. We will do this by: i)determining the functional relationship of heterochromatin and nuclear architecture ii)by determining the effects of artificially inducing heterochromatin on cell potency during development and iii)by determining the mechanisms that regulate heterochromatin formation in the embryo. We anticipate that our studies will unravel fundamental mechanims on how chromatin states regulate cell potency during reprogramming. By uncovering such mechanisms, we expect to reveal new insights that will be useful to induce epigenetic reprogramming of differentiated cells. Our results will therefore lead to key contributions in the fields of stem cell, developmental biology, human reproduction, chromatin biology and epigenetics.

Keywords: epigenetics,cell potency,mouse embryo,chromatin,heterochromatin,genome reprogramming,histone
Advanced Immunization Technologies (ADITEC)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Denmark,United Kingdom,Germany,France,United Kingdom,Italy,Switzerland,France,Sweden,Netherlands,United States,Netherlands,Austria,Netherlands,Switzerland,Iceland,Ireland,Sweden,Austria,United Kingdom,Belgium,Italy,Norway,Netherlands
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2017-09-30
Duration (months): 72.0
Total project cost (EUR): 41115267.95
EU funding (EUR): 29980670.0
Participants: 52
Project status: CLOSED

Vaccines so far have been developed mostly by following an empiric approach. To prevent and possibly cure unresolved and emerging infectious diseases we need to fully exploit the potential of the human immune system. Progress in science and technology makes it possible to achieve what was previously deemed impossible. The scope of this project is to produce knowledge necessary to develop novel and powerful immunization technologies for the next generation of human vaccines. This goal requires a multidisciplinary approach in which diverse but complementary scientific disciplines and technologies converge. Therefore some of the most competitive European research groups from public institutions and biotechs have agreed to join forces in ADITEC, together with top US groups on systems biology and adjuvants to support this enterprise. A systems biology approach will be used to study licensed and experimental vaccines in patient characterization studies and in clinical trials, to investigate the effect of adjuvants, vectors, formulations, delivery devices, routes of immunization, homologous and heterologous prime–boost schedules, as well as the impact of host factors such as age, gender, genetics and pathologies. Animal models will be used to complement human studies, and to select novel immunization technologies to be advanced to the clinic. To address these issues in a coordinated manner, ADITEC is organised on a matrix structure in which research themes and experimental approaches feed into each other. Training curricula will be created to impact on the formation of the next generation of EU researchers in the field. ADITEC scientists and institutions are part of the “Sclavo Vaccines Association” (SVA), which is dedicated to vaccines and vaccine research. SVA, acting as the coordinating institution, guarantees the long-term commitment and sustainability of this initiative, beyond the duration of ADITEC itself.

Keywords: vaccines,genomics,adjuvants,systems biology,immunization technologies,human immunology
Algal Bloom Dynamics: From Cellular Mechanisms to Trophic Level Interactions (INFOTROPHIC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: Israel
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1999648.0
EU funding (EUR): 1999648.0
Participants: 1
Project status: CLOSED

Marine phytoplankton are the basis of marine food webs and are responsible for nearly 50% of the global annual carbon-based primary production. Since phytoplankton exert such a global-scale influence on climate, we are interested in understanding what controls their cell fate during bloom “boom and bust” dynamics. Despite their importance, the molecular basis for their ecological success is still in its infancy. In recent years, the wealth of genomic information from marine microbes, coupled with molecular resources and analytical tools, provide an unprecedented opportunity to address fundamental questions about their unique evolutionary history and ecological role. Nevertheless, there is a critical need to “decode” the genomic resources and translate them into cellular mechanisms, community structure and, eventually, to their role in ecosystem function. This proposed research aims to provide novel insights into the role of a chemical-based “arms race” that mediates and structures the microbial interactions in the marine environment. We will dissect unexplored signaling pathways employed by phytoplankton during sensing and acclimation to changes in their environment. Our overarching objective is to unravel the role of infochemicals and related gene products in regulating phytoplankton surveillance systems in response to environmental stress conditions. We will focus on the three major biotic interactions of key dominant algal groups in the oceans; intercellular signaling in diatoms, host-virus interactions in coccolithophores and predator-prey interactions. We will provide a suite of cellular probes and metabolic biomarkers that will allow in situ detection of chemical signaling and biotic interactions in the oceans and will highlight their role in shaping microbial food webs. Our vision is to provide novel cellular concepts and molecular tools to the link between the intricate mechanisms of cell signaling and stress response, and large biogeochemical cycles.

Keywords: phytoplankton,marine virology,stress responses,signal transduction,oxidative stress,chemical signaling,molecular ecology,marine microbiology
Nanotechnology based cochlear implant with gapless interface to auditory neurons (NANOCI)

Framework: FP7 — Cooperation
Programme: Nanosciences, Nanotechnologies, Materials and new Production Technologies - NMP
Destination: Nanosciences and Nanotechnologies
Action type: Collaborative project
Countries involved: Switzerland,Germany,Sweden,Finland,Israel,Austria
Call:  (FP7-NMP-2011-SMALL-5, 2011)
Start date: 2012-09-01
End date: 2015-08-31
Duration (months): 36.0
Total project cost (EUR): 4914955.0
EU funding (EUR): 3599853.0
Participants: 9
Project status: CLOSED

Over 60 million of citizens in the EU suffer from hearing loss with its associated restrictions. In severe cases, hearing can only be restored by surgically implanting a neuroprosthesis called cochlear implant, which directly stimulates the auditory nerve. The bottleneck for optimal stimulation is caused by the anatomical gap between the electrode array and the auditory neurons in the inner ear. As a consequence, current devices are limited through (i) low frequency resolution, hence poor sound quality and (ii), strong signal amplification, hence high energy consumption responsible for significant battery costs and for impeding the development of fully implantable systems. Recent findings indicate that auditory nerve fibres can grow under neurotrophin stimulation towards the electrodes, which opens the door to address all issues simultaneously. NANOCI aims at developing a neuroprosthesis with a gapless interface to auditory nerve fibres. The neurites will be attracted and guided by an innovative, nanostructured gel matrix containing diffusible and surface-bound neurotrophic compounds towards the functionalized, neurotrophic electrode array surface. The long-lasting operation without interface degradation, reduced biofouling and improved conductivity will be achieved by nanostructuring the array surface using (i) various functional nanomaterials, including carbon nanotubes, combined with (ii) structuration methodologies such as ion implantation and sacrificial nanoparticle embedding in parylene, SOLID (solid on liquid deposition) encapsulation, and sonochemistry. Components will be validated using appropriate bioassays including human auditory neurons in vitro. In parallel, software models will be developed to exploit the bidirectional, gapless interface. Fusing all developments, an animal-grade, pilot nanoCI-device is manufactured and tested in vivo. This will allow to assess the feasibility of a future, cost-efficient, and fully implantable neuroprosthesis with substantially increased sound quality.

Keywords: cochlear implant,gapless interface,neuroprosthesis,nanostructuration of surface,biofunctionalization,nanoparticles,hearing loss,modelling,bidirectional implant,stem cells,antifouling surface
Role of Secondary Sensory Cortices in Emotional Memory Storage/Retrieval (RSSCEMSR)

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: Italy
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1116000.0
EU funding (EUR): 1116000.0
Participants: 1
Project status: CLOSED

Sensory stimuli, like odors, sound and colors, acquire positive or negative value through their association with rewards or punishments, a process called “emotional learning”. Although we know a great deal about how the brain analyses sensory information, we know relatively little about how sensory representations become linked with values and where such emotional memory is stored. Recently, we have demonstrated that higher order sensory cortices are necessary for the long-term storage of aversive memories. We hypothesized that such cortices represent the link between the neural sites that elaborate the physical features of sensory stimuli and the areas elaborating affective information. The present study is aimed at elucidating this issue. First, we will investigate if sensory cortices are mainly involved in the storage of aversive memories or alternatively if they participate also to the encoding of hedonic memories, i.e. if the brain normally uses higher order sensory cortices in order to allocate emotional positive as well negative memories. Then, we will address the crucial issue of whether and how these areas encode the emotional meaning that sensory stimuli acquire with the experience. Finally, we will study the functional dialogue that may occur during emotional memory storage/retrieval between sensory cortices and subcortical nuclei. To tackle these topics, we will employ a multidisciplinary approach made of the combination of behavioural, electrophysiological, immunohistochemical and confocal analyses. In our aim, the results obtained will provide new and important information about the brain circuitry that stores affective memories. In particular, they could led to the idea that higher-level sensory cortices encode the emotional value acquired by sensory stimuli and thus through their connections with other cortical and subcortical centres they enable identical sensory stimuli to trigger different emotional responses depending on past emotional experience

Keywords: emotional learning and memory,sensory cortex
Molecular and Structural Biology of Bacterial Transformation (MOLSTRUCTTRANSFO)

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-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1405149.0
EU funding (EUR): 1405149.0
Participants: 1
Project status: CLOSED

A common form of gene transfer is the vertical gene transfer between one organism and its offspring during sexual reproduction. However, some organisms, such as bacteria, are able to acquire genetic material independently of sexual reproduction by horizontal gene transfer (HGT). Three mechanisms mediate HGT in bacteria: conjugation, transduction and natural transformation. HGT and the selective pressure exerted by the widespread use antibiotics (in medicine, veterinary medicine, agriculture, animal feeding, etc) are responsible for the rapid spread of antibiotic resistance genes among pathogenic bacteria. In this proposal, we focus on bacterial transformation systems, also named competence systems. Natural transformation is the acquisition of naked DNA from the extracellular milieu. It is the only programmed process for generalized genetic exchange found in bacteria. This highly efficient and regulated process promotes bacterial genome plasticity and adaptive response of bacteria to changes in their environment. It is essential for bacterial survival and/or virulence and greatly limits efficiency of treatments or vaccine against some pathogenic bacteria. The architecture and functioning of the membrane protein complexes mediating DNA transfer through the cell envelope during bacterial transformation remain elusive. We want to decipher the molecular mechanism of this transfer. To attain this goal, we will carry out structural biology studies (X-ray crystallography and high resolution electron microscopy) as well as functional and structure-function in vivo studies. We have the ambition to make major contributions to the understanding of bacterial transformation. Ultimately, we hope that our results will also help to find compounds that could block natural transformation in bacterial pathogens.

Keywords: bacterial secretion. dna transport. electron microscopy.
Evaluation of Osteoarthritis Progression in a Patient-Specific Manner using Magnetic Resonance Imaging and Computational Modeling (OAPROGRESS)

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: Finland
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1303056.0
EU funding (EUR): 1303056.0
Participants: 1
Project status: CLOSED

Background Osteoarthritis (OA) is one of the most prevalent disorders of the musculoskeletal system. In OA, articular cartilage degenerates and its structure and mechanical properties change, but monitoring or predicting the progression of OA has not been possible. Magnetic resonance imaging (MRI) is a potential tool for the imaging of joint tissues, estimating cartilage structure and diagnostics of OA, whereas joint loading and estimation of stresses/strains within joint tissues necessitates computational modeling. It would be a major breakthrough if one could develop a technique where, based on MRI and computational modeling, prediction and evaluation of OA progression of a patient under a certain loading condition would be possible. Objectives 1) to combine MRI with computational modeling for the estimation of stresses and possible failure points within human knee joints, and 2) to develop second generation adaptive models of articular cartilage for the prediction of altered tissue structure and composition during OA progression. For the model validation, cartilage structure, composition and biomechanical properties as well as cell responses in situ are characterized. At the end of the project these main aims will be merged 3) to estimate the effect of loading on cartilage degeneration during the progression of OA in a patient-specific manner. Significance Combining MRI information of joint tissues with computational modeling, we develop a tool to evaluate the effect of different interventions on stresses in human joints. By combining this tool with an adaptive model that can estimate the effect of loading on cartilage composition and structure, we hope to be able to predict changes in cartilage properties during OA progression in a patient-specific manner several years ahead. This would help in decision making of clinical treatments and interventions (conservative or surgical) for the prevention or further progression of OA.

Keywords: articular cartilage,knee joint,osteoarthritis,magnetic resonance imaging,computational modeling,fibril reinforced,adaptation,degeneration,microscopy,mechanical testing,chondrocytes
Evolution and Development of Bacterial Communication (EVODEVOQUORUM)

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: Israel
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1497996.0
EU funding (EUR): 1497996.0
Participants: 1
Project status: CLOSED

Bacterial cooperation underlies many bacterial traits of practical interest. Many social traits of bacteria are regulated by inter-cellular signalling pathways, generally known as quorum sensing (QS). QS has been proposed as novel target for anti-virulence treatment. To this aim, there is a need to better understand the mechanisms of QS and their social and evolutionary impact. While the basic schemes of a single quorum sensing pathway acting in homogenous conditions are well understood, the system’s level function of QS regulatory networks can only be appreciated by considering the role phenotypic and genetic variability has on shaping the network’s structure and function. Phenotypic variability in complex communities may arise from division of labour between cells and environmental gradients and substantially impact the way cells secrete and interpret QS signals. Genetic variability in QS networks may lead to multiple social relations between cells of different genotypes including cross-talks, interception, manipulation and quenching of signals. This will affect the population structure and performance. The proposed project will study the function of QS signalling in heterogeneous communities. Phenotypic variability and its impact on QS function will be studied in a spatially inhomogeneous cooperating system. Genetic variability will be studied at the macro and micro-scales in a bacterial species showing rapid diversification of their QS networks. Finally, we will rationally design strains with superior ‘cheating’ strategies that can invade and eliminate a cooperative population. Throughout this project, we will use a combination of experimental techniques from microbiology, socio-biology, genetics and microscopy together with mathematical analysis tools from systems biology, population genetics and game theory, to study bacterial cooperation and its dependence on the underlying communication network, social complexity and environmental variation.

Keywords: microbial genetics,phenotypic variability,genetic variability,social evolution,quorum sensing,time-lapse microscopy,microbial development,synthetic biology,ecology.
Reprogramming cell identity to develop new therapies against Inherited Metabolic Disorders of the liver (RELIEVE-IMDS)

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-2011-StG_20101109, 2011)
Start date: 2012-12-01
End date: 2017-11-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Liver diseases are becoming one of the most common causes of mortality in developing countries, and orthotopic liver transplantation is the only available treatment. However, this procedure carries implies indefinite immunosupression treatment associated with heavy side effects and eventual rejection. Furthermore, an increasing number of patients die while on the liver transplant waiting list due to the shortage of donor livers. Hepatocyte transplantation recently became an alternative to transplantation for the treatment of life-threatening Ineherithed Metabolic Diseases (IMDs) of the liver. However, this approach is also hampered by the lack of donors and by the difficulty in expending hepatocytes in vitro. Therefore, developing alternative source of hepatocytes represents a major challenge for the regenerative medicine field. Pluripotent stem cells generated from reprogrammed somatic cells (human Induced Pluripotent Stem Cells or hIPSCs) represent an advantageous solution since they can proliferate indefinitely in vitro while maintaining their capacity to differentiate into a broad number of cell types including hepatocytes. In addition, hIPSCs could enable the production of patient specific cells fully immuno-compatible with the original donor thereby avoiding the need for immune suppressive treatment. Here, we propose to systematically address the limitations preventing the use of hIPSCs for cells based therapy of IMDs. We will first develop novel methods to generate “better” hIPSCs fully compatible with clinical applications and to differentiate them into adult hepatocyes. In parallel, we will establish a novel approach for editing the mammalian genome and to correct the genetic defects associated with IMDs. Finally, we will validate the safety and the functionality of hIPSCs derived hepatocytes in vivo. Overall this comprehensive study will aim to provide the first proof of principle that hIPSCs could be useful in novel therapies against IMDs.

Keywords: pluripotent stem cells,reprogramming,differentiation and transdifferentiation,liver,hepatocytes.