Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Molecular mechanisms of persistent antigenic stimulation in cytomegalovirus infection (CMVAGSTIMULUS)

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: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2016-09-30
Duration (months): 66.0
Total project cost (EUR): 1498456.0
EU funding (EUR): 1498456.0
Participants: 1
Project status: CLOSED

Cytomegalovirus (CMV) is a ubiquitous herpesvirus, latently persisting in the majority of the adult population worldwide. In these hosts, CMV-specific memory cells dominate the immune memory compartment. It follows that CMV-specific T-cells dominate the memory compartment of the majority of the human population worldwide. I propose to define within this project the molecular mechanisms driving the inflation of CMV-specific T-cells. My central hypothesis is that expression levels of CMV peptides during latency, along with the avidity of T-cell receptors for peptide MHC complexes, define the amplitude of T-cell responses. A corollary hypothesis is that vigorous T-cell responses in CMV infection are defined by factors that drive CMV gene expression during latency, such as inflammatory stimuli. This hypothesis will be verified in a model of in vivo CMV latency and immune monitoring. We will benefit from state-of-the-art inducible genetic systems, where recombinant mouse CMV will be deployed in transgenic mice. In latently infected mice, we will induce or suppress the expression of immunodominant CMV genes, and define downstream effects on T-cell response kinetics. In parallel, we will define the T-cell responses to high and low avidity peptides. Understanding the mechanisms driving the strong T-cell response to CMV is of outstanding biological and clinical relevance. If strong T-cell responses may be redirected to target heterologous antigens of interest, CMV-based vaccine vectors might potentially allow the development of HIV or tumor vaccines. On the other hand, it is speculated that the control of latent CMV may overcommit the aging immune system and exhaust the T-cell repertoire. Given the CMV pervasiveness, discerning the mechanisms of its T-cell induction may define novel molecular targets for rejuvenation strategies. In either case, the proposed research has groundbreaking potential in the field of infection and immunity.

Keywords: cytomegalovirus,t-lymphocyte,latency,recombinant dna,mirna,cre-recombinase
Physiology of the adult carotid body stem cell niche (CBSCS)

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: Spain
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1476000.0
EU funding (EUR): 1476000.0
Participants: 1
Project status: CLOSED

The discovery of adult neural stem cells (NSCs) has broaden our view of the physiological plasticity of the nervous system, and has opened new perspectives on the possibility of tissue regeneration and repair in the brain. NSCs reside in specialized niches in the adult mammalian nervous system, where they are exposed to specific paracrine signals regulating their behavior. These neural progenitors are generally in a quiescent state within their niche, and they activate their proliferation depending on tissue regenerative and growth needs. Understanding the mechanisms by which NSCs enter and exit the quiescent state is crucial for the comprehension of the physiology of the adult nervous system. In this project we will study the behavior of a specific subpopulation of adult neural stem cells recently described by our group in the carotid body (CB). This small organ constitutes the most important chemosensor of the peripheral nervous system and has neuronal glomus cells responsible for the chemosensing, and glia-like sustentacular cells which were thought to have just a supportive role. We recently described that these sustentacular cells are dormant stem cells able to activate their proliferation in response to a physiological stimulus like hypoxia, and to differentiate into new glomus cells necessary for the adaptation of the organ. Due to our precise experimental control of the activation and deactivation of the CB neurogenic niche, we believe the CB is an ideal model to study fundamental questions about adult neural stem cell physiology and the interaction with the niche. We propose to study the cellular and molecular mechanisms by which these carotid body stem cells enter and exit the quiescent state, which will help us understand the physiology of adult neurogenic niches. Likewise, understanding this neurogenic process will improve the efficacy of using glomus cells for cell therapy against neurological disease, and might help us understand some neural tumors.

Keywords: stem cells,self-renewal,differentiation,neurogenesis,peripheral nervous system,cancer,neurodegeneration,neurological disease
Chromosome Segregation and Aneuploidy (LONGCHROM)

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: Spain
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-06-01
End date: 2017-05-31
Duration (months): 72.0
Total project cost (EUR): 1058610.0
EU funding (EUR): 1058610.0
Participants: 1
Project status: CLOSED

Accurate partitioning of the genetic material during cell division is critical for genetic stability. Defects in chromosome segregation produce aneuploidy, an unequal distribution of chromosomes between daughter cells, which is cause of developmental defects, and one of the cancer hallmarks. To ensure error-free transmission of chromosomes, feedback control systems verify that processes at each stage of the cycle have been completed before progression into the next stage. In particular, the spindle assembly checkpoint prevents initiation of anaphase until chromosomes attach properly to the spindle, whereas the NoCut checkpoint, which I identified, delays cytokinesis until chromosome segregation is complete. The discovery of NoCut, which is conserved from yeast to humans, reveals that eukaryotic cells monitor chromosome segregation during anaphase. The molecular mechanisms of this, and potentially other anaphase feedback controls remain obscure. The goal of this proposal is to achieve a detailed understanding of the mechanisms coordinating chromosome segregation and cytokinesis. Key to this task will be the experimental manipulation of chromosome architecture in budding yeast, which allows the generation of cells with extra long chromosome arms. Using this strategy, we have already uncovered one novel feedback system, which monitors axial chromosome compaction during anaphase. We will investigate this and other anaphase controls through a multidisciplinary approach, which combines genetic techniques with state-of-the-art live cell microscopy, genomics and proteomics. We will characterize the feedback mechanism controlling chromosome compaction, and the molecular basis of chromosome segregation errors during anaphase. The relevance of these novel processes will be confirmed by analysis of cell division in animal cells and in a Drosophila tumour model. These approaches will advance our understanding of how eukaryotic cells prevent aneuploidy and tumorigenesis.

Keywords: cytokinesis anaphase chromosome condensation
Multidrug resistance and the evolutionary ecology of insect immunity (EVORESIN)

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,United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2016-03-31
Duration (months): 66.0
Total project cost (EUR): 1292502.0
EU funding (EUR): 1292502.0
Participants: 2
Project status: CLOSED

I will investigate the hypothesis that antimicrobial peptides in insects deal with persistent infections and/or prevent the evolution of resistant bacterial mutants. This will be achieved by looking at two hitherto unrelated areas within a single conceptual and experimental framework: (a) how to prevent the evolution of bacterial resistance against antimicrobials? (b) Why is it adaptive for insects to exhibit long lasting costly immune responses? This research takes a novel approach to understand the evolution of drug resistance in pathogens, one of the most important applied evolutionary questions of our times. Insects produce potent antimicrobials that are considered as future novel antibiotic drugs and provide insight into a multidrug treatment shaped by natural selection. Elucidating the evolution of integrated immune responses will greatly enhance the understanding of immunity in insects, the most speciose metazoan taxon of great importance to human health (vectors) and nutrition (pollinators). I will use the beetle Tenebrio molitor to examine the temporal dynamics of an antibacterial response using proteomics. I will build on this using two series of experiments manipulating the antimicrobial response in-vivo, using RNAi gene knockdowns, and in in-vitro, using synthesised Tenebrio antimicrobials will be carried out. These experiments will investigate the response of the model pathogen Staphyloccocus aureus to the changes in the beetle s multidrug response. S. aureus resistance to these experimental selection arenas will be studied at the phenotypic and genomic level. The results from this research program will (a) inform antibiotic strategies in medical and veterinary science and (b) will change the way we understand the evolution of (insect) immunity

Keywords: resistance evolution,antibiotics,insect immunity
Deep Tissue Optoacoustic Imaging for Tracking of Dynamic Molecular and Functional Events (DYNAMIT)

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: 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): 1452650.0
EU funding (EUR): 1452650.0
Participants: 1
Project status: CLOSED

The ability to visualize biological processes in living organisms continuously, instead of at discrete time points, holds a great promise for studies of functional and molecular events, disease progression and treatment monitoring. Optical spectrum is particularly attractive for biological interrogations as it can impart highly versatile contrast of cellular and sub-cellular function as well as employ highly specific contrast agents and markers not available for other modalities. However, technical limitations arising from intense light scattering in living tissues bound the main-stream of high resolution optical imaging applications to microscopic studies at shallow depths that do not allow the exploration of the full potential of novel classes of agents for volumetric imaging of entire organs, small animals or human tissues. To overcome limitations of the current imaging techniques, this proposal aims to develop a novel high performance optoacoustic imaging technology and explore its groundbreaking potential for neuroimaging and monitoring of cardiovascular disease. I will undertake a substantial technological step that will bring optoacoustic imaging to a real time (video rate) high resolution performance level the like of which has not existed so far. The resulting technique will be able to image several millimeters to centimeters into living small animals and potentially humans, with both high spatial resolution and sensitivity, being independent of photon scattering. This will make it suitable for attaining high dynamic contrast in intact tissues and an ideal candidate for both intrinsic and targeted biomarker-based imaging. It is hypothesized that these unparalleled imaging capabilities will allow observations of new classes of dynamic interactions at different time scales, from relatively slow varying inflammation-related molecular events to video rate visualization of neuronal activity in deep brain regions, otherwise invisible with other imaging methods.

Keywords: optoacoustic imaging,dynamic interactions,cardiovascular imaging,molecular imaging,photoacoutics,neuroimaging,tomographic methods,optical imaging,image reconstruction,fast processing
Global Research in Paediatrics (GRIP)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Network of Excellence
Countries involved: Italy,United States,United Kingdom,Netherlands,United Kingdom,France,Italy,Netherlands,Spain,Poland,Switzerland,Finland,Netherlands,Canada,Japan,Switzerland
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2011-01-01
End date: 2017-06-30
Duration (months): 78.0
Total project cost (EUR): 12637322.83
EU funding (EUR): 9999999.79
Participants: 23
Project status: CLOSED

Paediatric drugs (PD) lack appropriate testing. Most drugs have inadequate information about dosing regimen, dose adjustment and how to administer them. These are longstanding problems that unquestionably require concerted efforts at the international level. Both the US and the EU have introduced paediatric legislation that facilitates participation of children in research and pharmaceutical innovation but initiatives are not always coordinated and often different approaches are used to deal with the same problems. The main aim of GRiP will be to implement an infrastructure matrix to stimulate and facilitate the development and safe use of medicine in children. This implementation entails active coordination of knowledge management efforts and integrated use of existing research capacity, whilst reducing the fragmentation and duplication of activities. The consortium will primarily focus on: 1) development of a Paediatric Clinical Pharmacology Training Program; 2) Validation and harmonisation of research tools specific for paediatrics; 3) Sharing of strategies and plans; 4) Use of ongoing/planned research studies to evaluate the feasibility of proposed research tools and strategies. GRiP brings together an exceptional range of high quality leaders and stakeholders that are very active in the context of EU and US paediatric medicines research. GRiP will mobilize 21 institutions as partners and at least another 16 major networks that represent several hundreds of clinical sites and a total of more than 1000 researchers across Europe, the US and Asia. The integration of the WHO, EMA and the NIH-NICHD associated networks, including the FDA, will be a major asset not just for an effective implementation of the network activities without duplication, but also for the rapid translation of GRiP deliverables into practice. This partnership will work closely with families to provide children with safe and effective medicines.

Keywords: paediatrics,research,international network,medicine,drug,clinical trial,paediatric regulation,training,neonates,databases
Passive membrane transport of organic compounds (PASSMEMBRANE)

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: United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2015-06-30
Duration (months): 55.0
Total project cost (EUR): 1193758.8
EU funding (EUR): 1193758.8
Participants: 1
Project status: CLOSED

Passive transport through lipid membranes is ubiquitous and fundamental in living systems. The aim of this proposal is to create novel biotechnological tools to study permeation of organic compounds through lipid membranes and protein pores. In particular, I will focus on strategies employed by living organisms to optimize and regulate permeation directly through their membranes. The fundamental principles are probed by creating macroscopic model systems for biological channels and membranes. Simultaneously, new microfluidic tools will allow for a screening of biological relevant organic compounds. Biotechnological experiments investigating permeation of organic molecules into single uni-lamellar vesicles will challenge the dogma of protein controlled membranes transport. Indole, an important signaling molecule for E. coli, is an ideal candidate to demonstrate the feasibility of a novel assay based on a combination of four technologies. Microfluidics provide the controlled environment, holographic optical tweezers confine single vesicles in three dimensions to facilitate ionic current detection and simultaneous auto-fluorescence detection. This unique combination will yield a scalable technology platform to test membrane permeation. However, a deeper understanding of the molecular basis for these passive transport processes is still elusive. Theory predicts that binding potentials for molecules in a protein channel, passive transport can be optimized. Combining microfluidics with holographic optical tweezers provides the optimal means to test this quantitatively. These model experiments will prove that passive transport can be enhanced and optimized by introducing binding sites in protein channels and membranes. Furthermore, the results will guide future design of e.g. antibiotics, DNA vaccines and membrane permeating drugs and fundamentally change our understanding of passive membrane transport.

Keywords: biophysics,lipid membranes,nanopores,optical tweezers,microfluidics,vesicles,drug transport
Macromolecular machines that regulate mRNA poly(A) tails: mechanisms of polyadenylation and deadenylation (POLYAMECHANISMS)

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: United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2016-12-31
Duration (months): 72.0
Total project cost (EUR): 1124064.0
EU funding (EUR): 1124064.0
Participants: 1
Project status: CLOSED

The objective of my laboratory is to understand the mechanisms of mRNA polyadenylation and deadenylation, thereby providing fundamental insight into the regulation of eukaryotic gene expression. These objectives will be met through an integrated, multidisciplinary approach combining structural, biochemical, biophysical and yeast genetic techniques. Specifically, I propose to establish how mRNA poly(A) tail position and length are determined by the Cleavage and Polyadenylation Factor (CPF) and by the Ccr4-Not complex. Gene expression is tightly regulated, both spatially and temporally. Traditionally, this has been studied through transcription but more recent work has shown that post-transcriptional mechanisms play extensive roles. Many of these post-transcriptional functions are mediated by poly(A) tails which are found on almost all eukaryotic mRNAs. The CPF and Ccr4-Not complexes influence poly(A) tails to regulate mRNA stability and the efficiency of translation. They also mediate the periodic expression of cell cycle-related genes, microRNA-targeted gene silencing and expression of maternal masked mRNAs in oocyte development. My work will address many of these functions and will have broad-ranging biological and technological implications including: a better understanding of gene expression and the newly-emerging field of post-transcriptional regulation, the development of new technologies to study multi-protein complexes and the identification of potential therapeutic targets.

Keywords: mrna polyadenylation mrna deadenylation multi-protein complex
Soft, Slimy, Sliding Interfaces: Biotribological Properties of Mucins and Mucus gels (3S-BTMUC)

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: Denmark
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 1432920.0
EU funding (EUR): 1432920.0
Participants: 1
Project status: CLOSED

Mucins are a family of high-molecular-weight glycoproteins and a major macromolecular constituent in slimy mucus gels that are covering the surface of internal biological tissues. A primary role of mucus gels in biological systems is known to be the protection and lubrication of underlying epithelial cell surfaces. This is intuitively well appreciated by both science community and the public, and yet detailed lubrication properties of mucins and mucus gels have remained largely unexplored to date. Detailed and systematic understanding of the lubrication mechanism of mucus gels is significant from many angles; firstly, lubricity of mucus gels is closely related with fundamental functions of various human organs, such as eye blinking, mastication in oral cavity, swallowing through esophagus, digestion in stomach, breathing through air way and respiratory organs, and thus often indicates the health state of those organs. Furthermore, for the application of various tissue-contacting devices or personal care products, e.g. catheters, endoscopes, and contact lenses, mucus gel layer is the first counter surface that comes into the mechanical and tribological contacts with them. Finally, remarkable lubricating performance by mucins and mucus gels in biological systems may provide many useful and possibly innovative hints in utilizing water as base lubricant for man-made engineering systems. This project thus proposes to carry out a 5 year research program focusing on exploring the lubricity of mucins and mucus gels by combining a broad range of experimental approaches in biology and tribology.

Keywords: mucin,mucus gels,biotribology,lubrication,water lubrication