Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Membrane sensors in the Arf orbit (ARFMEMBRANESENSORS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: France
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2015-04-30
Duration (months): 48.0
Total project cost (EUR): 1997321.0
EU funding (EUR): 1997321.0
Participants: 2
Project status: CLOSED

Cellular organelles are continuously remodelled by numerous cytosolic proteins that associate transiently with their lipid membrane. Some distort the bilayer, others change its composition, extract lipids or bridge membranes at distance. Previous works from my laboratory have underlined the importance of membrane sensors, i.e. elements within proteins that help to organize membrane-remodelling events by sensing the physical and chemical state of the underlying membrane. A membrane sensor is not necessarily of well-folded domain that interacts with a specific lipid polar head: some intrinsically unfolded motifs harboring deceptively simple sequences can display remarkable membrane adhesive properties. Among these are some amphipathic helices: the ALPS motif with a polar face made mostly by small uncharged polar residues, the Spo20 helix with several histidines in its polar face and, like a mirror image of the ALPS motif, the alpha-synuclein helix with very small hydrophobic residues. Using biochemistry and molecular dynamics, we will compare the membrane binding properties of these sequences (effect of curvature, charge, lipid unsaturation); using bioinformatics we will look for new motifs, using cell biology we will assess the adaptation of these motifs to the physical and chemical features of organelle membranes. Concurrently, we will use reconstitution approaches on artificial membranes to dissect how membrane sensors contribute to the organization of vesicle tethering by golgins and sterol transport by ORP proteins. We surmise that the combination of a molecular ¿switch¿, a small G protein of the Arf family, and of membrane sensors permit to organize these complex reactions in time and in space.

Keywords: lipid membrane,amphipathic helix,membrane curvature,membrane tethering,sterol transport,alps motif,synuclein,phosphatidic acid
Regulation of gene expression in mammalian mitochondria (GENEMIT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Germany,Sweden
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 3110000.0
EU funding (EUR): 3110000.0
Participants: 2
Project status: CLOSED

The mitochondrial network produces the bulk part of the energy mammalian cells need through the oxidative phosphorylation process. The importance of mitochondria is underscored by the fact that deficient oxidative phosphorylation causes a wide number of genetic diseases. It is also heavily implicated in age-associated disease and ageing. Expression of mammalian mtDNA is of key importance for maintaining mitochondrial oxidative phosphorylation but studies of the poorly understood regulation of mammalian mitochondrial gene expression offer substantial experimental challenges. In the late 1990s, we felt that the challenges associated with understanding mammalian mtDNA gene expression could only be tackled by a broad interdisciplinary scientific approach. We therefore started collaboration between the Larsson (expertise in mouse genetics, in vivo physiology and cell biology) and Gustafsson laboratories (expertise in biochemistry, recombinant in vitro systems, structural biology) that has been ongoing for more than a decade. The success of this collaborative effort is documented by many joint publications in high-profile journals. Most importantly, we have together molecularly defined the basal mtDNA transcription initiation machinery and discovered a novel repressor, MTERF3, of mtDNA transcription. In this proposal, we present a series of unpublished results showing quite unexpected complexity in the regulation of mtDNA expression. An important part of our proposed work will be to establish how the different levels of regulation of mtDNA gene expression communicate to achieve a coordinated response to physiological stimuli.

Keywords: mitochondria,biochemistry,in vitro system,mouse model
Evolution of Pathogen and Host Diversity (DIVERSITY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2017-05-31
Duration (months): 72.0
Total project cost (EUR): 1670632.0
EU funding (EUR): 1670632.0
Participants: 1
Project status: CLOSED

The study of host-pathogen systems is of central importance to the control of infectious disease, but also provides unique opportunities to observe evolution in action. Many pathogen species have diversified under selection pressures from the host; conversely, genes that are important in host defence also exhibit high degrees of polymorphism. This proposal divides into two parts: (1) the evolution of pathogen diversity under host immune selection, and (2) the evolution of host diversity under pathogen selection. I have developed a body of theoretical work showing that discrete population structures can arise through immune selection rather than limitations on genetic exchange. The predictions of this framework concerning the structure and dynamics of antigenic, metabolic and virulence genes will be empirically tested using three different systems: the bacterial pathogen, Neisseira meningitidis, the influenza virus, and the malaria parasite, Plasmodium falciparum. The current theory will also be expanded and modified to address a number of outstanding questions such whether it can explain the occurrence of influenza pandemics. With regard to host diversity, we will be attempting to validate and extend a novel framework incoporating epistatic interactions between malaria-protective genetic disorders of haemoglobin to understand their intriguing geographical distribution and their mode of action against the malarial disease. We will also be exploring the potential of mechanisms that can organise pathogens into discrete strains to generate patterns among host genes responsible for pathogen recognition, such as the Major Histocompatibility Complex. The co-evolution of hosts and pathogens under immune selection thus forms the ultimate theme of this proposal.

Keywords: pathogen evolution,host resistance genes,immune selection
Vocal template computations in the songbird brain (VOTECOM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Switzerland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-11-30
Duration (months): 66.0
Total project cost (EUR): 2011440.0
EU funding (EUR): 2011440.0
Participants: 1
Project status: CLOSED

Song learning in oscine birds shares several characteristics with human language learning: it relies on social interaction, active participation, and error feedback, and must take place within a critical period. Songbirds learn their songs from a tutor: they memorize a template of tutor song and compare their own song to that template until a good match is achieved. The existence of a song template in the songbird brain has been clearly demonstrated in deafening, isolation, and lesion experiments, and therefore the songbird is one of the best animal models for unravelling neural principles of template-based vocal learning. Currently we know very little about neural mechanisms in the brain that support template-based learning. In songbirds, our knowledge about the template is limited to behavioural aspects that favour or hinder faithful imitation and to evidence about the brain areas in which the template is stored. Elusive about the template remains its neural representation, as well as the manner in which it is used for evaluating the plastic juvenile songs. Here we propose for the first time a set of experiments aimed at identifying neural mechanisms of template computations including template storage, template recall, and template-based evaluation of auditory feedback. We test the hypothesis that during singing, juvenile birds recall a memory of tutor song and use that memory to analyze and evaluate their own songs. In the zebra finch, our goal is to find a neural correlate of this memory trace in higher auditory association areas. We believe that our studies will provide fundamental insights into how the brain monitors its behavioral output and compares it to some desired output, for which a sensory template has been memorized.

Keywords: zebra finch,sleep,learning,language,memory
Melanopsin-based vision in health and disease (MELOVISION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2017-04-30
Duration (months): 72.0
Total project cost (EUR): 2499636.0
EU funding (EUR): 2499636.0
Participants: 1
Project status: CLOSED

It is now >10 years since the remarkable discovery that photoreception in the mammalian retina occurs outside of rod and cone cells. In that time we have learnt a great deal about the melanopsin expressing retinal ganglion cells (mRGCs) that provide this non-rod non-cone photoreception, and about their extensive contribution to sub-conscious light responses. However, one idea that has persisted is that these mRGCs play little if any role in visual perception. Exciting new data challenge that view. Thus, we have recently described an extraordinarily extensive mRGC input to the primary visual pathway. This provides ~40% of neurones in the mouse visual thalamus with melanopsin signals, superimposed upon more conventional visual information. The discovery of this unexpected sensory input to the mammalian visual system raises several important questions: What does it contribute to vision? How is the melanopsin signal brought to the thalamus and how is it propagated/processed through higher visual centres? Does melanopsin help people with retinal degeneration (in which mRGCs long outlive rods and cones) to see? Could optimising melanopsin vision offer a new strategy for improving vision in these people? We propose addressing these questions by using state-of-the-art neurophysiological and anatomical techniques in mice. Our overarching objectives are Objective 1: What does melanopsin contribute to vision? Objective 2: How is melanopsin vision impacted by retinal degeneration?

Keywords: retina,vision,melanopsin,chronobiology,circadian
Cancerbiome: Characterization of the cancer-associated microbiome (CANCERBIOME)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Germany
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-07-01
End date: 2016-06-30
Duration (months): 60.0
Total project cost (EUR): 2233740.0
EU funding (EUR): 2233740.0
Participants: 1
Project status: CLOSED

Deep environmental sequencing (metagenomics) will be used to characterize microbial communities associated with 3 different cancer types: cervical cancer, oral squamous cell carcinoma and colorectal cancer. For all 3 types, non-invasive molecular diagnostics and prognostics are feasible via utilization of vaginal, oral and faecal samples, respectively. The project consequently aims to identify microbial markers in these ¿readouts¿ that correlate with cancer presence or progression. Microbial markers can be individual species or specific community compositions, but also particular genes or pathways. The microbial communities will be sampled locally at tumor surfaces and in healthy control tissues. After DNA extraction and sequencing, a complex bioinformatics pipeline will be developed to characterise the microbiomes and to identify the cancer-specific functional and phylogenetic markers therein. For colorectal cancer, the project intends to go into more details in that it tries i) to establish a correlation of microbiota with cancer progression and it ii) explores differences between distinct cancer subtypes. For each of the 3 cancer types, at least two samples from 40 individuals will be sequenced (as well as controls) at a depth of at least 5Gb each using Illumina technology. This is expected to be sufficient for the identification of microbial markers and also allows superficial genotyping of the individuals at ca 2-3x coverage as a by-product (the samples will contain considerable amounts of human DNA). Further analyses will be designed to study the potential of certain microbial species or community compositions to enhance or even cause one or more of the 3 cancers. The discovery of such causations will open up research towards directed antimicrobial treatment.

Keywords: human cancer microbiome
The role of myelinating glia in preserving axon function (AXOGLIA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Germany
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 2477800.0
EU funding (EUR): 2477800.0
Participants: 1
Project status: CLOSED

In the human brain, the 'bottleneck' of neuronal integrity are long axonal projections, which are often the first to degenerate in neuro-psychiatric diseases. We have discovered in mice that oligodendrocytes and Schwann cells are not only essential for the formation of myelin, but also for the functional integrity of axons and their long-term survival. However, the underlying molecular mechanisms have remained obscure. We propose to use experimental mouse genetics to study neuron-glia interactions and to identify axonal signals that control the normal behaviour of myelinating oligodendrocytes. We will then test our hypothesis that axons require oligodendrocytes not only for myelination, but also for the metabolic support of impulse propagation and fast axonal transport. Based on striking pilot observations, we will analyze the mechanisms by which ensheathing glial cells respond to axonal distress and ask in vivo whether they provide glycolysis end products to axonal mitochondria for energy production ('lactate shuttle'). We will also investigate whether myelin lipids are a readily accessible energy store in glia and explore a speculative hypothesis that N-acetyl aspartate is an aspartate-based shuttle of acetyl-CoA residues. If this proposal is successful, we will begin to understand the true function of oligodendrocytes in endogenous neuroprotection and as bystanders of neuronal disease and normal brain aging. This would initiate a paradigm shift for the role of myelinating glial cells, and could open the door for novel therapeutic strategies in a broad range of neurodegenerative diseases, which pose a major burden on the EC health care system.

Keywords: axonal transport,myelin sheath,neuropathy,leukodystrophy,adrenoleukodystrophy
The Impact of Privatization on the Mortality Crisis in Eastern Europe (PRIVMORT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: United Kingdom,United Kingdom,Hungary
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-09-01
End date: 2017-08-31
Duration (months): 72.0
Total project cost (EUR): 3483058.0
EU funding (EUR): 3483058.0
Participants: 4
Project status: CLOSED

After the collapse of Communism 3 to 7 million ¿excess deaths¿ occurred, comparable to the toll exacted by Stalin. While public health research has uncovered a great deal about the proximal causes of these deaths, identifying alcohol and psychosocial stress as key causes, incredibly few studies have attempted to address the variation in these proximal causes. Why did people in some countries start to abuse alcohol much more and experience greater stress than in others? A recent article in The Lancet by the PI linked radical privatization policies to increased mortality via increased unemployment using longitudinal cross-national statistics. This article generated great controversy, and soon a critics claimed that with different specifications the model was not sufficiently robust, or that the cross-national data could conceal an ecological fallacy or miss another cause. Our study will provide decisive evidence on this debate by proposing a new methodology for studying the impact of economic policies on public health, and in so doing advancing an emerging new research tradition we call the Political Economy of Public Health. We will do this by way of developing an innovative methodology of establishing a convenience cohort study, based on the Brass indirect method traditionally used by demographers in countries without reliable vital registration data. The Brass method uses interviews with random population samples to collect data on deaths of their relatives to estimate key population mortality parameters. Our innovation is to select one-company towns that were privatized in a radical way, and matching them with towns which had a different privatization experience. In this way we can generate micro-data to test the privatization thesis. We will also be able to measure the importance of occupation on mortality. This new research method promises new tools to study the impact of large-scale politicaal, economic and organizational change on population health.

Keywords: privatization mortality post-communism
Molecular Nanotechnology for Life Science Applications: QUantitative Interactomics for Diagnostics, PROteomics and QUantitative Oncology (QUIDPROQUO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: Italy
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-07-01
End date: 2016-06-30
Duration (months): 60.0
Total project cost (EUR): 2979700.0
EU funding (EUR): 2979700.0
Participants: 2
Project status: CLOSED

The main goal of this proposal is to introduce innovative devices and protocols (based on nano- manipulation, the response of micro-(nano-)mechanical oscillators and nano-fluidics) to carry out, precise, high throughput, high sensitivity, and low cost interactomic measurements. We aim at measuring, in parallel, the concentration of up to several proteins or non-coding RNA molecules, in samples down to the single cell level, following the real time concentrations of several biomarkers in patient-derived samples down to femto-molar concentrations, and single-circulating-tumor-cell resolution. We plan to develop our program a) by applying the principles and practice of intrinsically differential measurements, e.g. by building a self-assembled nano-devices that provide robust outputs measurable with topographic AFM imaging, electrochemical measurements, or gel electrophoresis, and b) by using the vertical equivalent of cantilever oscillators (pillars) that we plan to use as quartz “microbalances” that are 10,000 time more sensitive than cantilevers w. r. t. measurable min. mass and 100 time more sensitive w. r. t. dilution. The proposal’s core strategy is to exploit the PI’s expertise in innovative instrumentation and his integrated physical chemistry know-how, leading a highly multi-disciplinary staff to closely interact with first class medical staff in hospital settings to solve, and validate the solution of, relevant medical problems by generating innovative and versatile sensing devices. For instance, the sensitivity of our sensors will allow protein or miRNA analysis from very small and homogeneous samples of tumor cells, as well as the ease identification circulating tumor cells (CTCs) for, in addition to improved cancer diagnostics, also the prediction of patient response to treatment. The convergence between chemistry and biology, through nanotechnology, physics and computational approaches, with medical diagnostics will enable our team to come up with more versatile and reliable diagnostic tools, while stimulating fundamental research in fields as diverse as stem cells differentiation and the study of cell physiopathology.

Keywords: physical-organic-chemistry biophysics biophysical-chemistry interactomics bioanalytical-chemistry
Systematic dissection of molecular machines and neural circuits coordinating C. elegans aggregation behaviour (ACMO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-04-01
End date: 2017-03-31
Duration (months): 72.0
Total project cost (EUR): 2439996.0
EU funding (EUR): 2439996.0
Participants: 1
Project status: CLOSED

Elucidating how neural circuits coordinate behaviour, and how molecules underpin the properties of individual neurons are major goals of neuroscience. Optogenetics and neural imaging combined with the powerful genetics and well-described nervous system of C. elegans offer special opportunities to address these questions. Previously, we identified a series of sensory neurons that modulate aggregation of C. elegans. These include neurons that respond to O2, CO2, noxious cues, satiety state, and pheromones. We propose to take our analysis to the next level by dissecting how, in mechanistic molecular terms, these distributed inputs modify the activity of populations of interneurons and motoneurons to coordinate group formation. Our strategy is to develop new, highly parallel approaches to replace the traditional piecemeal analysis. We propose to: 1) Harness next generation sequencing (NGS) to forward genetics, rapidly to identify a molecular ¿parts list¿ for aggregation. Much of the genetics has been done: we have identified almost 200 mutations that inhibit or enhance aggregation but otherwise show no overt phenotype. A pilot study of 50 of these mutations suggests they identify dozens of genes not previously implicated in aggregation. NGS will allow us to molecularly identify these genes in a few months, providing multiple entry points to study molecular and circuitry mechanisms for behaviour. 2) Develop new methods to image the activity of populations of neurons in immobilized and freely moving animals, using genetically encoded indicators such as the calcium sensor cameleon and the voltage indicator mermaid. This will be the first time a complex behaviour has been dissected in this way. We expect to identify novel conserved molecular and circuitry mechanisms.

Keywords: neural circuits,genetically encoded indicators,genetics,c. elegans,signal processing