Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Molecular Basis of Mammalian Egg-Sperm Interaction (GAMETE RECOGNITION)

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: Sweden
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1499281.6
EU funding (EUR): 1499281.6
Participants: 1
Project status: CLOSED

At the dawn of the 21st century, our knowledge of the molecular mechanism of mammalian fertilization remains very limited. Different lines of evidence indicate that initial gamete recognition depends on interaction between a few distinct proteins on sperm and ZP3, a major component of the extracellular coat of oocytes, the zona pellucida (ZP). On the other hand, recent findings suggest an alternative mechanism in which cleavage of another ZP subunit, ZP2, regulates binding of gametes by altering the global structure of the ZP. Progress in the field has been hindered by the paucity and heterogeneity of native egg-sperm recognition proteins, so that novel approaches are needed to reconcile all available data into a single consistent model of fertilization. Following our recent determination of the structure of the most conserved domain of sperm receptor ZP3 by X-ray crystallography, we will conclusively establish the basis of mammalian gamete recognition by performing structural studies of homogeneous, biologically active recombinant proteins. First, we will combine crystallographic studies of isolated ZP subunits with electron microscopy analysis of their filaments to build a structural model of the ZP. Second, structures of key egg-sperm recognition protein complexes will be determined. Third, we will investigate how proteolysis of ZP2 triggers overall conformational changes of the ZP upon gamete fusion. Together with functional analysis of mutant proteins, these studies will provide atomic resolution snapshots of the most crucial step in the beginning of a new life, directly visualizing molecular determinants responsible for species-restricted gamete interaction at fertilization. The progressive decrease of births in the Western world and inadequacy of current contraceptive methods in developing countries underscore an urgent need for a modern approach to reproductive welfare. This research will not only shed light on a truly fundamental biological problem, but also constitute a solid foundation for the reproductive medicine of the future.

Keywords: mammalian fertilization,egg-sperm interaction,zona pellucida,infertility,contraception
Coordination Action in support of the implementation of a Joint Programming Initiative for Combating Neurodegenerative Diseases, in particular Alzheimer’s disease (JUMPAHEAD)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Coordination and support actions
Countries involved: France,United Kingdom,Germany,Germany,Ireland,Netherlands,Italy,Türkiye,Spain,Hungary,Sweden,Slovakia
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-09-01
End date: 2014-08-31
Duration (months): 48.0
Total project cost (EUR): 2618089.66
EU funding (EUR): 2000000.0
Participants: 13
Project status: CLOSED

The objective of the Coordination Action JUMPAHEAD is to support the implementation of the pilot Joint Programming Initiative on combating neurodegenerative diseases, in particular Alzheimer’s disease (JPND). Neurodegenerative disorders are incurable and debilitating conditions that result in progressive degeneration or death of nerve cells. Of these, the dementias are responsible for the greatest burden of disease, and today in Europe over 7 million people suffer from Alzheimer's disease and related disorders, with this figure expected to double by 2020 as the European population ages. Although our understanding of the mechanisms of neurodegenerative disease has greatly improved over the past few years, there is no effective treatment able to stop or even slow down the deterioration of brain functions associated with these disorders. To tackle this pan-European health and societal challenge more effectively, 22 EU countries have launched the JPND. This is an innovative programme based on a common vision to improve the impact of their combined research effort to accelerate progress towards new treatments, identify preventative strategies, and improve patient care. JUMPAHEAD will build the foundations for this initiative by supporting the development and implementation of a Strategic Research Agenda, as well as its dissemination and evaluation. This will be achieved under the direction of the JPND Management Board. The output of JUMPAHEAD over its 36 month duration will include innovative ways of pooling national expertise and resources and the establishment of closer and robust research collaborations among the participating States in the field of neuro-degeneration research. JUMPAHEAD will contribute to the European Research Area by addressing fragmentation and improving integration of national research programmes to offer a competitive and attractive image of European research prosecuted for the greatest benefit of Europe’s populations and economies.

Keywords: pilot joint programming initiative,neurodegenerative diseases,alzheimer,strategic research agenda
Analysis of flow regulated angiogenesis during zebrafish development (ZEBRAFISHANGIO)

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: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2015-09-30
Duration (months): 60.0
Total project cost (EUR): 1423000.0
EU funding (EUR): 1423000.0
Participants: 1
Project status: CLOSED

Angiogenesis, or the sprouting of blood vessels from pre-existing ones is a key process in shaping the vasculature. So far, angiogenesis research has mainly focused on identifying genetic players. My proposed research takes a completely novel approach towards understanding angiogenesis by addressing the question how physiological factors, such as changes in blood flow dynamics, influence endothelial biology. I will furthermore address the question if there is an interaction between genetic and physiological influences during angiogenesis. My proposed research will tackle these outstanding questions in endothelial biology using several cutting edge technologies. First, I will perform long term time lapse imaging of the growing vasculature using 2-Photon microscopy. Second, I will use an innovative methodology employing zinc finger nuclease mediated gene targeting to rapidly generate mutant zebrafish in genes implicated in mediating the effects of hemodynamics on angiogenesis. Third, I will laser ablate individual blood vessels in living zebrafish embryos to alter blood flow patterns and study the influence of those changes on angiogenesis. These challenging technological advancements will make it possible for the first time to understand how physiological factors aid in shaping the forming vascular system. These findings will have broad applicability to angiogenic processes in many different vascular beds and developmental time points. Importantly, the mechanisms at play during vascular development in the embryo are reactivated in the adult in situations of pathological angiogenesis, such as tumor progression or ischemia. Therefore, applying this knowledge to angiogenesis occuring in pathological settings will provide us with new avenues for improved disease treatments.

Keywords: zebrafish,angiogenesis,chemokines,hemodynamics,zinc finger nucleases,transgenesis,2-photon microscopy
Sensory-motor circuits in marine zooplankton and early evolution of the nervous system (PROTOBRAIN)

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: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2015-09-30
Duration (months): 60.0
Total project cost (EUR): 1270800.0
EU funding (EUR): 1270800.0
Participants: 1
Project status: CLOSED

Animal nervous systems evolved in a marine environment at the dawn of animal life, and diversified during the Cambrian explosion', one of the most spectacular events in the history of life. Remarkably little is known about early stages of the evolution of neuronal circuits and nervous systems. Simple marine planktonic organisms, in particular ciliated larvae of various marine invertebrates, can give us insights into how simple nervous circuits of marine organism function and may have evolved. The proposed project aims at investigating the nervous system of ciliated animal larvae using an integrative approach combining the fields of molecular biology, neurobiology, behaviour, marine ecology and evolution. As such, the project aims at pioneering an entirely new field of interdisciplinary investigations, the neurobiology of marine zooplankton. We will use a cultured marine annelid as our main model species, and several 'satellite' species to give a comparative perspective to our investigations. Our objective is to understand the anatomy and function of neuronal circuits that regulate the planktonic migration of ciliated zooplankton larvae. We will be able to address this at various levels, linking molecules to neuron types, neurons to larval behaviours and behaviours to marine ecology. Our aim is to get the first detailed systems level understanding of the nervous system of a marine ciliated larva.

Keywords: evo-devo,marine zooplankton,sensory-motor circuits,genomics,comparative neurobiology,nervous system and eye evolution
More Medicines for Tuberculosis (MM4TB)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Switzerland,Sweden,Italy,United Kingdom,United Kingdom,France,Russian Federation,Italy,Slovakia,Hungary,India,Italy,Spain,Spain,Germany,France,South Africa,United States
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2011-02-01
End date: 2016-07-31
Duration (months): 66.0
Total project cost (EUR): 16698641.15
EU funding (EUR): 11873052.0
Participants: 27
Project status: CLOSED

The More Medicines for Tuberculosis (MM4TB) consortium evolved from the highly successful FP6 project, New Medicines for TB (NM4TB), that delivered a candidate drug for clinical development two years ahead of schedule. Building on these firm foundations and exploiting its proprietary pharmacophores, MM4TB will continue to develop new drugs for TB treatment. An integrated approach will be implemented by a multidisciplinary team that combines some of Europe's leading academic TB researchers with two major pharmaceutical companies and four SMEs, all strongly committed to the discovery of anti-infective agents. MM4TB will use a tripartite screening strategy to discover new hits in libraries of natural products and synthetic compounds, while concentrating on both classical and innovative targets that have been pharmacologically validated. Whole cell screens will be conducted against Mycobacterium tuberculosis using in vitro and ex vivo models for active growth, latency and intracellular infection. Hits that are positive in two or more of these models will then be used for target identification using functional genomics technologies including whole genome sequencing and genetic complementation of resistant mutants, yeast three hybrid, click chemistry and proteomics. Targets thus selected will enter assay development, structure determination, fragment-based and rational drug design programs; functionally related targets will be found using metabolic pathway reconstruction. Innovative techniques, based on microfluidics and array platforms, will be used for hit ranking, determining rates of cidality and confirming mechanism of action. Medicinal chemistry will convert leads to molecules with drug-like properties for evaluation of efficacy in different animal models and late preclinical testing.

Keywords: tuberculosis,drug discovery
Understanding the basis of cerebellar and brainstem congenital defects: from clinical and molecular characterisation to the development of a novel neuroembryonic in vitro model (CBCD)

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: Italy
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-08-01
End date: 2018-03-31
Duration (months): 80.0
Total project cost (EUR): 1367960.0
EU funding (EUR): 1367960.0
Participants: 3
Project status: CLOSED

Cerebellar and brainstem congenital defects (CBCDs) are heterogeneous disorders with high pre-and post-natal mortality and morbidity. Their genetic basis and pathogenetic mechanisms are largely unknown, hampering patients’ diagnosis and management and family counselling. This project aims at improve current understanding of primary CBCDs through a multidisciplinary approach combining innovative clinical, neuroimaging, molecular and functional studies, that will be articulated in four workpackages: WP1- Clinical and neuroimaging studies: collection of detailed data and biological samples from a large cohort of patients covering a broad spectrum of CBCDs, neuroimaging classification based on magnetic resonance imaging and tractography, genotype-phenotype correlates and follow-up studies. WP2 - Molecular studies on mendelian CBCDs: high-throughput resequencing of ciliary genes to identify pathogenic mutations and genetic modifiers in patients with ciliopathies, identification of novel disease genes, mutation analysis of genes causative of other mendelian CBCDs. WP3 - Molecular studies on sporadic CBCDs: identification of cryptic chromosomal rearrangements by high resolution SNP-array analysis, selection and mutation analysis of candidate genes mapping to the rearranged regions. WP4 - Functional studies: optimisation of a novel neuroembryonic in vitro model derived from mouse embryonic stem cells, to test the role of known and candidate disease genes (from WP2 and 3) on cerebellar and brainstem development, define the pathways in which they are involved and the effect of disease-causative mutations. This project is expected to improve the current CBCD nosology, identify novel genes and mechanisms involved in cerebellar and brainstem development that are responsible for mendelian or sporadic defects, expand the available tools for pre- and post-natal diagnosis and identify clinical-genetic correlates and prognostic indexes.

Keywords: cerebellum,brainstem,congenital defects,mutation screening,copy number variations,linkage,genotype-phenotype correlates,stem cells,ciliopathies
Spatiotemporal regulation of chromosome segregation fidelity (PRECISE)

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: Portugal
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1485097.0
EU funding (EUR): 1485097.0
Participants: 1
Project status: CLOSED

At any given moment, 250 million cells are dividing in the human body through an essential process known as mitosis. Inaccuracy of mitosis leads directly to aneuploidy (gain or loss of chromosomes), a hallmark of several cancers and birth defects. Mitotic fidelity is controlled by the spindle assembly checkpoint (SAC), a signaling pathway that delays the progression of mitosis to ensure that all chromosomes are attached to mitotic spindle microtubules (MTs). Central to this activity, the kinetochore (KT), a minute structure on each replicated sister-chromatid, promotes the rapid turnover of MTs to correct potential attachment errors during early mitotic stages. Upon anaphase onset, the KT then switches to bind MTs with higher affinity, so that the energy derived from their depolymerizing plus ends helps driving chromosome motion to the poles. While the molecular basis of the KT-MT interface is only now starting to be elucidated, how the multiple KT activities are regulated throughout mitosis remains unknown. Here we propose to dissect from a molecular perspective how the interaction between spindle MTs and KTs controls chromosome segregation fidelity in space and time. For this purpose we will combine the power of biochemical analysis and genome-wide RNAi screens with the detailed functional investigation of already identified candidate genes using state-of-the-art live cell microscopy and pilot laser microsurgery tools in animal cells. Additionally, we have in place all the necessary conditions to investigate the physiological significance of chromosome segregation errors and evaluate respective outcomes using unique mammalian model systems. With this synergistic approach we aim to unveil the molecular routes of aneuploidygenesis and their implications to human health.

Keywords: mitosis,mitotic spindle,kinetochore,spindle checkpoint,error correction
Genetics of Resistance to Malaria Parasites in the Mosquito Anopheles gambiae (MALARES)

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: France,France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-06-01
End date: 2017-05-31
Duration (months): 72.0
Total project cost (EUR): 1489600.0
EU funding (EUR): 1489600.0
Participants: 2
Project status: CLOSED

Anopheles gambiae mosquitoes are major vectors of Plasmodium falciparum, a protozoan parasite that causes the most severe form of human malaria in Africa. With an estimated 250 million infected people every year and another 3.3 billion at risk, malaria remains one of the biggest scourges of humanity. One of the promising approaches to fight malaria is the control of vector competence that determines the ability of a mosquito to transmit the disease. The fact that mosquito strains that are resistant to the parasites can be selected indicates that genetic factors in mosquitoes limit parasite development. Here we propose to use laboratory infection models to decipher the complex genetic networks that sustain mosquito resistance to P. berghei and P. falciparum. In these models, genotype-to-genotype interactions and environmental variability are limited, two features that are essential to efficiently dissect the genetic control of a complex trait. The parallel identification of loci conferring resistance to P. berghei and to P. falciparum will be crucial to unravel the conserved and species-specific aspects of mosquito parasite interactions at the molecular level. We will further evaluate the contribution of the identified genes and networks to vector competence in natural mosquito populations. Because resistance naturally occurs in mosquito populations, this project has implications for the design of novel strategies and/or for the improvement of existing ones to reduce malaria transmission.

Keywords: malaria,anopheles gambiae,plasmodium,mosquito resistance
Charting the landscape of brain development by large-scale single-cell transcriptomics and phylogenetic lineage reconstruction (BRAINCELL)

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: Sweden
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1496032.0
EU funding (EUR): 1496032.0
Participants: 1
Project status: CLOSED

Embryogenesis is the temporal unfolding of cellular processes: proliferation, migration, differentiation, morphogenesis, apoptosis and functional specialization. These processes are well understood in specific tissues, and for specific cell types. Nevertheless, our systematic knowledge of the types of cells present in the developing and adult animal, and about their functional and lineage relationships, is limited. For example, there is no consensus on the number of cell types, and many important stem cells and progenitors remain to be discovered. Similarly, the lineage relationships between specific cell types are often poorly characterized. This is particularly true for the mammalian nervous system. We have developed (1) a reliable high-throghput method for sequencing all transcripts in 96 single cells at a time; and (2) a system for high-throughput phylogenetic lineage reconstruction. We now propose to characterize embryogenesis using a shotgun approach borrowed from genomics. Tissues will be dissected from multiple stages and dissociated to single cells. A total of 10,000 cells will be analyzed by RNA sequencing, revealing their functional cell type, their lineage relationships, and their current state (e.g. cell cycle phase). The novel approach proposed here will bring the powerful strategies pioneered in genomics into the field of developmental biology, including automation, digitization, and the random shotgun method. The data thus obtained will bring clarity to the concept of ‘cell type’; will provide a first catalog of mouse brain cell types with deep functional annotation; will provide markers for every cell type, including stem cells; and will serve as a basis for future comparative work, especially with human embryos.

Keywords: lineage reconstruction