Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Neurocomputational determinants of decision urgency in humans (URGENCY)

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: United Kingdom
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-06-30
Duration (months): 66.0
Total project cost (EUR): 1182176.0
EU funding (EUR): 1182176.0
Participants: 1
Project status: CLOSED

A central question in the behavioural, cognitive and neural sciences is how humans choose between available alternatives (Does this patient have flu, or meningitis? Should I go on holiday to Spain, or Scotland?). However, much less attention has been devoted to the question of when an agent should decide. Longer deliberation is more likely to lead to better decisions (because it allows greater accumulation of decision-relevant evidence) but it also incurs a cost (because it delays reinforcement, and increases the chance that deadlines will be missed). Humans adjust their decision strategy to match the urgency with which a decision should be made, but how they do so is unknown. In the proposed research, we ask how humans compute the urgency associated with simple perceptual categorisation judgments, and use functional brain imaging to identify neural circuits involved in these computations. Our approach to this question is grounded in formal mathematical models of the decision process, allowing us to compare human performance to that of an ideal observer that computes decision urgency in order to maximise economic outcome. Using tools from experimental psychology, we measure the sensitivity of healthy individuals to quantities that are relevant for computing decision urgency. We will then use functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to ask where they are encoded in the human brain. Subsequently, we turn our attention to individuals who are prone to make impulsive decisions, using individual difference and pharmacological manipulations. We ask which decision-relevant information is computed inappropriately in impulsivity, and use fMRI and MEG to ask which brain regions may be responsible for atypical computations. This new ‘computational neuropsychiatry’ approach will allow us to move towards a neural and computational account decision-making deficits in disorders such as addiction and ADHD.

Keywords: decision-making,categorisation,impulsivity,reward,functional magnetic resonance imaging (fmri),magnetoencephalography (meg),visual perception,ideal observer.
MEIOtic inSIGHT: Deciphering the engine of heredity (MEIOSIGHT)

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
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1492663.0
EU funding (EUR): 1492663.0
Participants: 1
Project status: CLOSED

Meiosis is an essential stage in the life cycle of sexually-reproducing organisms. Indeed, meiosis is the specialized cell division that reduces the number of chromosomes from two sets in the parent to one set in gametes, while fertilization restores the original chromosome number. Meiosis is also the stage of development when genetic recombination occurs, thus being the heart of Mendelian heredity. Increasing our knowledge on meiotic mechanisms, in addition to its intrinsic interest, may have also important implications for agriculture and medicine. In the last decade Arabidopsis emerged as one of the prominent models in the field of meiosis. Indeed, the meiotic field benefits greatly from a multi-model approach with several kingdoms represented, highlighting both conserved mechanisms and variation around the theme. Arabidopsis did not emerge only as a representative of its phylum, but is also a very good model to study meiosis in general, notably because of the possibility of large scale genetic studies and the availability of large mutant collections and wide range of molecular and cytological tools. In this project we aim to use original approaches to decipher much further meiotic mechanisms, by isolating a large number of novel genes and characterizing their functions in an integrated manner. To identify new meiotic functions, we will use innovative genetic approaches. The first work package is based on a new suppressor screen strategy, taking advantage of a unique and favourable situation in Arabidopsis. The second is an unprecedented screen that exploits the fact that we can now synthesize haploids in a higher eukaryote. The third work package aims to fully exploit the available transcriptome data. In the fourth work package we will use these new genes to deeply decipher the meiotic mechanisms in an integrated manner.

Keywords: meiosis,recombination,sister chromatid cohesion,cell cycle
Specificity of Rc3h1/2 proteins in post-transcriptional control of immunity and autoimmune disease (RC3H1/2-SPECIFICITY)

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-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1392400.0
EU funding (EUR): 1392400.0
Participants: 2
Project status: CLOSED

We are constantly protected by our adaptive immune system. Its functioning requires precise control of gene expression in lymphocytes, since deregulation can cause autoimmune diseases (affecting ~5% of our population) as well as allergic reactions (~9-16%, with increasing incidence). Post-transcriptional control of gene expression is crucial in many immune decisions, however the determinants of specificity in this type of regulation are less well defined. The recently described Rc3h1 or Roquin protein prevents the development of autoimmune disease in mice. Rc3h1 destabilizes the mRNA of the inducible costimulator (ICOS), a co-receptor on T cells. ICOS is critical in the germinal center reaction in which T cell help selects B cells making high affinity antibodies. However, the molecular interactions of this posttranscriptional regulation and the pathways that specify such repressor/target relations are unsolved, and they are the focus of my work in this proposal. Rc3h1 is an essential factor of peripheral T cell tolerance, whereas the role of its paralog Rc3h2 has not been addressed. We have recently shown that Rc3h1 is an RNA binding-protein that recognizes the 3’UTR of ICOS mRNA. Our preliminary data suggest that Rc3h2 is co-expressed in T cells and binds ICOS mRNA indistinguishably in vitro, however it does not repress ICOS. Major challenges are therefore to define how the Rc3h1/2 proteins recognize cis-elements in the RNA, which cofactors they require for repression and how these proteins exert diverse functions. My project proposes to pursue three aims: (1) to describe Rc3h1/2 target recognition in the T cell transcriptome, (2) to globally identify the essential genes in this pathway of post-transcriptional repression and (3) to analyze redundant and unique roles of Rc3h1 and Rc3h2 proteins in the mouse embryo, the hematopoietic system and in models of immunity and spontaneous development of autoimmune disease.

Keywords: autoimmunity,germinal center reaction,rna/protein interaction,post-transcriptional repression,p body function,costimulation
International Research Consortium on Dengue Risk Assessment, Management, and Surveillance (IDAMS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,United Kingdom,United Kingdom,Switzerland,Switzerland,Malaysia,Indonesia,Cuba,Brazil,United Kingdom,Ghana,Venezuela, Bolivarian Republic of,Bangladesh,Mexico,United States,El Salvador,Netherlands
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-09-01
End date: 2017-02-28
Duration (months): 66.0
Total project cost (EUR): 7706132.79
EU funding (EUR): 5999213.0
Participants: 18
Project status: CLOSED

The overall concept of this research project is to assemble a consortium of international experts working together to develop new and innovative tools to be applied to the control of dengue in a global context. The core of the application focuses on parallel strategies aimed at: • improving diagnosis and clinical management of dengue through two linked work packages designed a) to identify readily available clinical and laboratory parameters and/or viral and immunological markers, that differentiate between dengue and other common febrile illness within 3 days of fever onset, and b) to identify any of the available markers that are predictive of the likelihood of evolving to a more severe disease course • assessing the risk of dengue spread though linked work packages focused on a) mapping and modelling techniques to define the current extent of dengue disease globally and to evaluate possible scenarios of spread or risk to previously uninfected regions in the future, and b) developing effective and affordable early warning and outbreak response systems. These four work packages are supported by a fifth work package dedicated to networking and translational activities to ensure that outputs from the various research activities are used to maximal advantage.

Keywords: dengue,control,diagnostic tools,clinical management,surveillance,modelling,risk of spread,asia,latin america,africa,networks
From Genome Integrity to Genome Plasticity: Dynamic Complexes Controlling Once per Cell Cycle Replication (DYNACOM)

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: Greece
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1531000.0
EU funding (EUR): 1531000.0
Participants: 1
Project status: CLOSED

Accurate genome duplication is controlled by multi-subunit protein complexes which associate with chromatin and dictate when and where replication should take place. Dynamic changes in these complexes lie at the heart of their ability to ensure the maintenance of genomic integrity. Defects in origin bound complexes lead to re-replication of the genome across evolution, have been linked to DNA-replication stress and may predispose for gene amplification events. Such genomic aberrations are central to malignant transformation. We wish to understand how once per cell cycle replication is normally controlled within the context of the living cell and how defects in this control may result in loss of genome integrity and provide genome plasticity. To this end, live cell imaging in human cells in culture will be combined with genetic studies in fission yeast and modelling and in silico analysis. The proposed research aims to: 1. Decipher the regulatory mechanisms which act in time and space to ensure once per cell cycle replication within living cells and how they may be affected by system aberrations, using functional live cell imaging. 2. Test whether aberrations in the licensing system may provide a selective advantage, through amplification of multiple genomic loci. To this end, a natural selection experiment will be set up in fission yeast . 3. Investigate how rereplication takes place along the genome in single cells. Is there heterogeneity amongst a population, leading to a plethora of different genotypes? In silico analysis of full genome DNA rereplication will be combined to single cell analysis in fission yeast. 4. Assess the relevance of our findings for gene amplification events in cancer. Does ectopic expression of human Cdt1/Cdc6 in cancer cells enhance drug resistance through gene amplification? Our findings are expected to offer novel insight into mechanisms underlying cancer development and progression.

Keywords: cell cycle,licensing,dna replication,genomic integrity,gene amplification,functional imaging,modelling,fission yeast,human cells,cancer
Neuromodulation of Oxygen Chemosensory Circuits in Caenorhabditis elegans (ELEGANSNEUROCIRCUITS)

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: Austria
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-06-30
Duration (months): 66.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

An animal’s decision on how to respond to the environment is based not only on the sensory information available, but further depends on internal factors such as stress, sleep / wakefulness, hunger / satiety and experience. Neurotransmitters and neuropeptides in the brain modulate neural circuits accordingly so that appropriate behaviors are generated. Aberrant neuromodulation is implicated in diseases such as insomnia, obesity or anorexia. Given the complexity of most neural systems studied, we lack good models of how neuromodulators systemically affect the activities of neural networks. To overcome this problem, I propose to study neural circuits in the nematode C. elegans, which is a genetically tractable model organism with a simple and anatomically defined nervous system. I will focus on the neural circuits involved in oxygen chemosensory behaviors. Worms can smell oxygen and they use this information to navigate through heterogeneous environments. This enables them to find food and to engage in social interactions. Oxygen chemosensory behaviors are highly modulated by experience and nutritional status, but the underlying mechanisms are not understood. I established behavioral assays that allow studying the modulation of oxygen behaviors in a rigorously quantifiable manner. I also acquired expertise in micro-fabrication technologies and developed imaging devices to measure the activity of neurons in live animals. The first two aims of this proposal focus on the application of these technologies to study (A) how neuropeptides mediate experience dependent modulation of oxygen chemosensory circuits; and (B) how food availability and nutritional status modulate the same neural circuits. Aim (C) is an innovative engineering approach in which I will develop new microfluidic technologies that allow the simultaneous recording of oxygen evoked behaviors and neural activity. This will be beneficial for aims A and B and will pave way for new future research directions.

Keywords: neural circuits behavior chemosensation chemotaxis oxygen neuromdulation neuropeptides neurohormones satiety neuroimaging bioengineering lab-on-a-chip microfluidics
Linking neural circuits to visual guidance in flying flies (FLYVISUALCIRCUITS)

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: Austria
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-12-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 2
Project status: CLOSED

The brain of a fly is capable of steering the animal through a complex environment at high relative speeds, avoiding stationary obstacles and moving predators. Because it is relatively easy to study how flies do this at several levels, from the behavioral to the cellular, fly vision has long been recognized as an ideal system to address a fundamental question in neuroscience- how does the distributed activity of neurons orchestrate animal-environment interactions to result in successful coordinated behavior? This work addresses this basic question with two related studies. The first concerns higher levels of visual processing and behavior. Do flies build a neural representation of nearby objects or, alternatively, is flight governed by a direct coupling of visual input into motor commands? The second identifies specific neurons responsible for visual guidance behaviors. This work involves the establishment of a new research activity in the EU by a Principal Investigator who is moving from a third country (the US) into the EU. It uses a unique high-throughput, virtual reality free flight arena in which flies are tracked in realtime by a computer vision system. With this technology, physically unmanipulated and unrestrained flies are automatically and repeatedly presented with arbitrary visual stimuli projected on the arena walls and floor. Thousands of digitized 3D flight trajectories are gathered, and behavioral experiments using this system will be combined with targeted genetic manipulation of the nervous system and analyzed to reveal the magnitude and reliability of effects. This will be accomplished by using molecular genetic techniques to selectively perturb individually identified neurons in the brain and measuring the effect on flight control in response to precisely specified visual stimuli. Thus, by utilizing controlled stimulus conditions and measuring behavioral responses in detail, the results will show the contribution of individual neurons to behavior.

Keywords: neurobiology,behavior,drosophila,vision,virtual reality,genetics,neural inactivation,psychophysics,neuroanatomy,machine learning,computer vision,spatial memory
The Ecology of Antibiotic Resistance (ARISE)

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: 2012-09-01
End date: 2018-08-31
Duration (months): 72.0
Total project cost (EUR): 1900000.0
EU funding (EUR): 1900000.0
Participants: 1
Project status: CLOSED

Main goal. We aim to understand the puzzling coexistence of antibiotic-resistant and antibiotic-sensitive species in natural soil environments, using novel quantitative experimental techniques and mathematical analysis. The ecological insights gained will be translated into novel treatment strategies for combating antibiotic resistance. Background. Microbial soil ecosystems comprise communities of species interacting through copious secretion of antibiotics and other chemicals. Defence mechanisms, i.e. resistance to antibiotics, are ubiquitous in these wild communities. However, in sharp contrast to clinical settings, resistance does not take over the population. Our hypothesis is that the ecological setting provides natural mechanisms that keep antibiotic resistance in check. We are motivated by our recent finding that specific antibiotic combinations can generate selection against resistance and that soil microbial strains produce compounds that directly target antibiotic resistant mechanisms. Approaches. We will: (1) Isolate natural bacterial species from individual grains of soil, characterize their ability to produce and resist antibiotics and identify the spatial scale for correlations between resistance and production. (2) Systematically measure interactions between species and identify interaction patterns enriched in co-existing communities derived from the same grain of soil. (3) Introducing fluorescently-labelled resistant and sensitive strains into natural soil, we will measure the fitness cost and benefit of antibiotic resistance in situ and identify natural compounds that select against resistance. (4) Test whether such “selection-inverting” compounds can slow evolution of resistance to antibiotics in continuous culture experiments. Conclusions. These findings will provide insights into the ecological processes that keep antibiotic resistance in check, and will suggest novel antimicrobial treatment strategies.

Keywords: microbial community,evolution
Pathogen and commensal immunity compared in a reversible infection model that uncouples immunity from pathogen immune evasion (REVERSIBLEINFECTION)

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: Switzerland
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1499992.0
EU funding (EUR): 1499992.0
Participants: 1
Project status: CLOSED

The research described in this proposal will use a novel reversible intestinal infection model developed in my laboratory (Hapfelmeier et al., 2010. Science 328:1705-1709) for the detailed study of the differences between intestinal commensal and pathogen induced immunity. In my earlier work this system allowed fully reversible intestinal exposure of germ-free animals with live bacteria so that the commensal-induced immunity could be uncoupled from persistent bacterial colonization. This permitted detailed quantitative and temporal analysis of host responses to encounter of live commensal bacteria. In the presented research project the reversible bacterial colonization model will be extended to produce a model of reversible intestinal infection with intestinal pathogenic bacteria to uncouple pathogen immunity from pathogen immune evasion. Most microbes we encounter are commensal bacteria that benignly colonize the intestinal lumen. The immune system is well adapted for commensal mutualism, and mutualism breakdown, as in inflammatory bowel disease, is relatively rare. In contrast, pathogenic bacterial encounters less frequent and countered with anti-pathogen immune defense and inflammation. During infection, the host-pathogen relationship is a competition between anti-bacterial immunity and pathogen immune evasion – the latter is well-studied, the former largely in systems where the pathogen proliferates and immune evasion overlays immunity. There is the need to experimentally uncouple pathogen immunity and pathogen immune evasion. Our novel approach permits a detailed comparative analysis of pathogen and commensal immune induction and will shed new light on the mechanisms of pathogen versus commensal immune recognition. This knowledge is critical for the design of efficient bacterial vaccines and the understanding of the abnormal immune responses directed against commensal microbes in chronic inflammatory diseases.

Keywords: mucosal pathogenic bacteria,commensal bacteria,iga,mucosal,immunity,immune evasion