Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Differentiation and role of Natural Killer cell subsets (DIRONAKI)

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: France
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-12-31
Duration (months): 72.0
Total project cost (EUR): 1340757.0
EU funding (EUR): 1340757.0
Participants: 1
Project status: CLOSED

NK cells are innate lymphocytes that play a role in the early response against intracellular pathogens and against tumors. Several NK cell subsets have been described in peripheral organs that correspond to discrete stages of in vivo maturation. How NK cells differentiate from early precursors and what are the specific functions of each NK cell subset are unresolved issues. Here, we propose a three-aim program to address these questions. First, we want to revisit the partition of the NK cell population that is currently based on surface markers of undefined function by looking at the expression of transcription factors (TF) essential for NK cell development and maturation, such as T-bet and Eomes, using novel TF reporter mice. This strategy should also allow us to identify very early steps of NK cell development (NK cell progenitors) that remain ill defined. Second, we will try and identify molecular mechanisms that induce transition between NK cell maturation stages. For this we will take advantage of a previous gene profiling analysis that pointed at several pathways and TF that were highly regulated during NK cell maturation. The role of these pathways and TF in the differentiation of NK cells will be measured using a novel Cre/lox system allowing NK-specific gene deletion. Detailed analysis of mouse mutants will be used to delineate the role of selected genes and pathways in NK cell differentiation. Third, we will compare patterns of migration, cytokine secretion, in vivo cytotoxicity and global gene expression by individual NK cell subsets during an airway infection by Influenza to get insight on the specific functions of NK cell subsets during immune responses. Altogether, the results of this study should provide developmental, molecular and functional evidences to support the physiological relevance of NK cell subsets. This may improve strategies that aim at manipulating NK cell function for the benefit of patients with cancer or chronic infectious diseases

Keywords: natural killer cells
New Oral Nanomedicines: Transporting Therapeutic Macromolecules across the Intestinal Barrier (TRANS-INT)

Framework: FP7 — Cooperation
Programme: Nanosciences, Nanotechnologies, Materials and new Production Technologies - NMP
Destination: Nanosciences and Nanotechnologies
Action type: Collaborative project
Countries involved: Spain,Ireland,Belgium,France,United Kingdom,Italy,France,Germany,Spain,Sweden,France,Switzerland,Ireland,Hungary
Call:  (FP7-NMP-2011-LARGE-5, 2011)
Start date: 2012-05-01
End date: 2017-04-30
Duration (months): 60.0
Total project cost (EUR): 10748102.64
EU funding (EUR): 8000000.0
Participants: 18
Project status: CLOSED

Despite the increasing number of macromolecules with potential impact in the treatment of devastating systemic diseases, these therapies have failed to deliver on their expectations because they cannot be administered in the fashion which is most cost efficient and has the highest patient compliance: the oral route. The availability of an oral form of administration could lead to a great improvement of classical therapies and it would also make a high number of new therapies feasible. To make this happen, the final objective of Trans-INT is to design nanocarriers specifically adapted to deal with the gastrointestinal ecosystem and use them for the development of new oral nanomedicines for diseases with high socioeconomic impact (i.e. metabolic diseases, pain medication). The concept behind TRANS-INT is the rational design of oral nanomedicines based on safety, mechanistic, bioengineering (multifunctional nanocarriers: high payload, drug protection, efficient drug transport, controlled release) and pharmaceutical technology criteria (scalable technology and stability). The project will start with nanocarrier platforms on which the partners have IPR and freedom to operate: nanocapsules, nanoparticles, micelles made of combinations of lipids, polypeptides and polysaccharides, continue with the optimization and redefinition of selected nanocarriers. It is expected to end with (i) at least one oral nanocarrier prototype with a comprehensive GLP-tox package, which could be applied for the delivery of a high number of peptide molecules, (ii) at least one nanomedicine fulfilling target product profile criteria, with a comprehensive preclinical evaluation package, (iii) substantial integrative knowledge on the feasibility and potential of oral nanocarriers and nanopharmaceuticals. TRANS-INT is expected to have a great impact no only from the new therapies/patients perspective but also from the innovation and EU industrial development perspective.

Keywords: oral administration,intestinal barrier,peptides,nanocarriers
Variability in the mutation rate of RNA viruses (VIRMUT)

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: Spain,Spain,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): 1432021.0
EU funding (EUR): 1432021.0
Participants: 3
Project status: CLOSED

RNA viruses are the fastest evolving entities in nature. Such rapid evolution is explained by their mutation rates, which are orders of magnitude higher than those of DNA organisms. The error-prone replication of RNA viruses also has public-health implications related to pathogenesis, antiviral research, or viral emergence. However, current mutation rate estimates vary by more than 100-fold across different RNA viruses and sometimes over one order of magnitude for the same virus, and the causes of this variation remain poorly understood. Here, we plan to investigate variability in the mutation rate of RNA viruses at different levels. First, polymorphic sites in viral polymerases could produce populations with heterogeneous mutation rates, and the spread of genotypes with altered mutation rates might influence viral fitness and disease progression. Second, spontaneous mutations might occur preferentially at some regions of the viral genome, and these mutational hotspots could match genome regions where the selective pressure imposed by the host is strongest, thereby increasing viral adaptability. Third, RNA viruses with different types of genomes, such as single-stranded versus double-stranded RNA or sense versus anti-sense genome polarity might differ in their susceptibility to nucleic-acid damage or host-mediated editing and thus, in their mutation rate. Fourth, RNA viruses with larger genomes might have evolved increased replication fidelity to compensate for their greater genetic load. To address these issues, we will use several biomedically relevant and/or model viruses, including HIV-1, hepatitis C virus, a rotavirus, a coronavirus and a bacteriophage. The experimental procedures will include in vitro replication fidelity assays, ex vivo infections using cell cultures, and analysis of patient samples by next-generation sequencing. This thorough and multilevel approach may reveal previously unrecognized mechanisms for generating diversity in RNA viruses.
Understanding the Long-Term fate of geologically stored CO2 (ULTIMATECO2)

Framework: FP7 — Cooperation
Programme: Energy
Destination: CO2 capture and storage technologies for zero emission power generation
Action type: Collaborative project
Countries involved: France,Germany,United Kingdom,Germany,France,Denmark,Italy,France,Netherlands,Netherlands,Switzerland,United Kingdom
Call:  (FP7-ENERGY-2011-1, 2011)
Start date: 2011-12-01
End date: 2015-11-30
Duration (months): 48.0
Total project cost (EUR): 5331268.0
EU funding (EUR): 4026120.0
Participants: 13
Project status: CLOSED

ULTimateCO2 will 1) significantly advance our knowledge of specific processes that could influence the long-term (LT) fate of geologically stored CO2 and 2) yield validated tools for predicting LT storage site performance. The 4-year collaborative programme will cover detailed lab, field and modelling studies of the main physical & chemical processes involved and their impacts in the LT: a) trapping mechanisms in the reservoir (structural, dissolution, residual, mineral), b) fluid-rock interactions and effects on mechanical integrity of fractured caprock and faulted systems and c) leakage due to mechanical & chemical damage in the well vicinity. Integration of the results will enable an assessment of overall LT behaviour of storage sites at regional scale in terms of efficiency & security, also including other important aspects, e.g. far-field brine displacement and fluid mixing. The LT prediction of CO2 evolution during geological storage will thus become more robust, not only by addressing the uncertainty associated with numerical modelling, but also by applying realistic contexts and scales. The latter will be ensured through close collaboration with at least two demonstration sites in deep saline sandstone formations: the onshore NER300 Ouest Lorraine candidate in France (ArcelorMittal GeoLorraine) and the offshore EEPR Hatfield site in UK (National Grid). ULTimateCO2 will develop recommendations for operators and regulators to enable a robust demonstration of the assessment of LT storage site performance. Scientific knowledge on the LT efficiency and safety of CO2 storage will be disseminated widely to a broad audience, so that not only operators of demo sites will benefit, but also other stakeholder groups, including policy makers and regulators, storage developers, investors, the scientific community, and representatives of the general public (NGOs and CCS initiatives), thus helping to improve public understanding.

Keywords: co2 storage,long-term fate,brine displacement,trapping mechanisms,fault mechanical integrity,well interface leakage,uncertainty assessment,demonstration sites
Bridging spatial and temporal resolution gaps in the study of cell division (DIVIMAGE)

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: Austria
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-03-01
End date: 2017-02-28
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Cell division underlies the growth and development of all living organisms. Following partitioning of bulk cytoplasmic contents by cleavage furrow ingression, dividing animal cells split by a distinct process termed abscission. Whereas a number of factors required for abscission have been identified in previous studies, it is not known by which mechanism they mediate fission of the intercellular bridge between the nascent sister cells. Here, we will establish correlative workflows of time-lapse imaging, super resolution fluorescence microscopy, electron tomography, and electrophysiological assays to bridge spatial and temporal resolution gaps in the study of abscission. We will further develop computational tools for image-based RNAi screening. With this, we aim to: 1) elucidate how membrane and cytoskeletal dynamics coordinately split the intercellular bridge; 2) uncover the signaling pathways controlling abscission timing. Failure in abscission can lead to aneuploidy and cancer. Elucidating its mechanism and temporal control is therefore of general biological and medical relevance. The computational and correlative imaging methods developed in this project will further provide the research community new possibilities for mechanistic studies in intact cells.

Keywords: cell division,cytokinesis,abscission,escrt-iii,spastin,live-cell imaging,super-resolution microscopy,electron tomography,rnai screening
Yeast symbionts of malaria vectors: from basic research to the management of malaria control (SYMBIOVEC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Italy
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-06-01
End date: 2017-05-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Advances in biotechnology propose innovative tools particularly relevant for public health application by genetic manipulation of microbial symbionts of arthropod vectoring disease. The symbiont engineering prevents the transmission of pathogens to human by interfering with their stage within the arthropod, thorough the expression of anti-pathogen effector molecules. This approach, defined paratransgenesis is simpler than the proposed engineering of the vector itself (transgenesis) and implies minor applicative and ethical concerns. Identification of good candidate for paratransgenesis has opened the way towards the investigation of microbes residing in the arthropod body, particularly those localised within the gut that often represents the locale in which pathogens transit or develop. Good paratransgenic candidates were already identified in the bug vectoring Chagas disease in South America and in the tse-tse fly vectoring sleeping sickness in Africa. As regard mosquitoes, responsible of tens of human infections including malaria, some interesting bacteria have been recognized as candidates for genetic manipulation, even if the ability of recombinant strains to cure mosquito has not been demonstrated yet in the field. Bacteria can be easily isolated, modified and reintroduced in the mosquito but secretion of antagonists by prokaryotic cell can represent a matter difficult to resolve. In this context endosymbiotic yeasts seem to be very appealing. Their genetic and cellular complexity makes yeasts as ideal tools for manipulation and bypasses many difficulties relative to the recombinant products releasing. On these bases, I have recently begun a study on the yeast microflora in mosquito. Particularly, I investigated the relationship between the yeast endosymbiont Pichia anomala and malaria vectors. Considering the special features of this yeast, I propose its use as paratransgenic tool for malaria control.

Keywords: mosquito-borne disease,malaria,pichia anomala
A Treatment-Oriented Research Project of NCL Disorders as a Major Cause of Dementia in Childhood (DEM-CHILD)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,Finland,United Kingdom,Italy,Germany,United Kingdom,Germany,India,Germany,Germany,Germany
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2014-09-30
Duration (months): 36.0
Total project cost (EUR): 3971419.6
EU funding (EUR): 2998795.0
Participants: 13
Project status: CLOSED

The DEM-CHILD project focusses on the main cause for childhood dementia in Europe, the neuronal ceroid lipofuscinoses (NCLs). The NCLs are neurodegenerative diseases characterized by dementia, blindness, epilepsy and physical decline leading to an early death of the patients. Since no cure is currently available, these disorders represent a serious social, medical, and economic challenge. To date, eight NCL genes have been characterised. There is evidence suggesting that further gene loci remain to be identified. NCLs are under-diagnosed in many countries around the world as there is an overall lack of research, early diagnosis, treatment and expert availability. Furthermore, due to their broad genetic heterogeneity it is difficult to collect large numbers of genetically similar patients. As such, large therapeutic studies required for advances in treatment are difficult to initiate. The DEM-CHILD project will combine the expertise of (i) recognized European research teams with (ii) high-technology SMEs, and will (iii) collaborate with Indian experts on the following objectives: (1) High-technology SMEs will develop innovative cost- and time-effective testing and screening methods for all NCLs in order to ensure early diagnosis and thereby prevention. (2) DEM-CHILD will collect the world’s largest, clinically and genetically best characterised set of NCL patients in order to study disease prevalence and precisely describe the natural history of the NCLs leading to the development of an evaluation tool for experimental therapy studies. (3) Novel biomarkers and modifiers of NCL will be identified to support the development of innovative therapies. (4) Focussing on the development of therapies for NCLs caused by mutations in intracellular transmembrane proteins, two complementary therapeutic strategies will be used and compared in eye and brain of mouse models: a) viral-mediated gene transfer and b) neural stem cell-mediated delivery of neuroprotective factors.

Keywords: childhood dementia,neurodegeneration,lysosomal storage disorders,neuronal ceroid lipofuscinoses,viral-mediated gene transfer therapy,neural stem cell-mediated delivery of neuroprotective factors
Nuclear Dynamic, Organization and Genome Stability (NDOGS)

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: 2012-02-01
End date: 2018-01-31
Duration (months): 72.0
Total project cost (EUR): 1499863.0
EU funding (EUR): 1499863.0
Participants: 1
Project status: CLOSED

The eukaryotic genome is packaged into large-scale chromatin structures occupying distinct domains in the cell nucleus. Nuclear compartmentalization has recently been proposed to play an important role in genome stability but the molecular steps regulated remain to be defined. Focusing on Double strand breaks (DSBs) in response to which cells activate checkpoint and DNA repair pathways, we propose to characterize the spatial and temporal behavior of damaged chromatin and determine how this affects the maintenance of genome integrity. Currently, most studies concerning DSBs signaling and repair have been realized on asynchronous cell populations, which makes it difficult to precisely define the kinetics of events that occur at the cellular level. We thus propose to follow the nuclear localization and dynamics of an inducible DSB concomitantly with the kinetics of checkpoint activation and DNA repair at a single cell level and along the cell cycle. This will be performed using budding yeast as a model system enabling the combination of genetics, molecular biology and advanced live microscopy. We recently demonstrated that DSBs relocated to the nuclear periphery where they contact nuclear pores. This change in localization possibly regulates the choice of the repair pathway through steps that are controlled by post-translational modifications. This proposal aims at dissecting the molecular pathways defining the position of DSBs in the nucleus by performing genetic and proteomic screens, testing the functional consequence of nuclear position for checkpoint activation and DNA repair by driving the DSB to specific nuclear landmarks and, defining the dynamics of DNA damages in different repair contexts. Our project will identify new players in the DNA repair and checkpoint pathways and further our understanding of how the compartmentalization of damaged chromatin into the nucleus regulates these processes to insure the transmission of a stable genome.

Keywords: dna repair,recombination,nhej,nuclear organization,chromatin dynamics
Mammalian Origin of replication – Genome-wide Mapping and Regulation (ORIGINOME)

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: 2011-12-01
End date: 2016-11-30
Duration (months): 60.0
Total project cost (EUR): 1499523.2
EU funding (EUR): 1499523.2
Participants: 1
Project status: CLOSED

Very little is known about the global organization and regulation of the replication program. Recent advances in genomic methods allow the genome-wide description of the time of replication in mammals. Nevertheless, the spatial information about replication initiations (origin of replication) is still sparse. Such information is crucial for studying mechanistic aspects of replication regulation since the time of replication is determined mainly by the time each origin is activated. In Originome I propose to develop novel genome-wide approaches that will allow origin mapping both in the cell population and the single cell levels. Applying these methods to multiple tissues, growth conditions and organisms, will put me in an excellent position for studying the regulation of the replication machinery. I am planning to combine bioinformatics, comparative genomics and reverse genetics tools to decipher the cis-acting elements that participate in the regulation of the replication program. Successful mapping of origins and characterization of their mode of regulation have broad implications not only in the field of DNA replication. First, replication stress is one of the initial causes of cancer. Therefore, I am planning to decipher the changes in the replication program that occur in response to stress in order to better understand the transformation process. Second, better understanding of replication regulation will allow studying systematically the association between time of replication, transcription and chromatin structure. Taken together, by moving the field of DNA replication from a descriptive into a mechanistic stage, Originome will set the stage for a variety of experimental approaches for deciphering replication organization and its effects on transcription, chromatin structure and cancer transformation.

Keywords: origin of replication,time of replication,optical mapping,recombineering,genome-wide approaches