Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Integral membrane proteins resolution of stoichiometry and structure (IMPRESS)

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: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2100155.0
EU funding (EUR): 2100155.0
Participants: 1
Project status: CLOSED

Our recent discovery, that large integral membrane protein complexes can survive intact in the mass spectrometer, prompts many new experiments to understand the mechanism of their release from micelles and to maximise the impact of this finding. We propose to examine the structure of membrane complexes after their release from micelles in the gas phase. We will apply ion mobility mass spectrometry to extract collision cross sections of membrane complexes of known structure and compare these with those calculated form atomic coordinates. Conditions will be optimised to minimise the distortion of structure. More controlled release of membrane complexes from micelles will be investigated using photo-activation. To do this we will explore properties of detergents incorporating chromophores, with infra red laser activation to activate the micelle selectively without perturbing the membrane protein complex. We also propose to develop methods for determining structures of lipids bound specifically in membrane protein interfaces and assess their effects on the stability and stoichiometry of the complex. To visualise these complexes in the absence of micelles we propose to 'soft land' membrane protein complexes on electron microscopy grids, targeting components by virtue of their mass to charge. We will apply these methods to some of the most challenging and controversial membrane protein complexes including EmrE, the intact ATP synthases, the M2 proton channel of the influenza A virus, the P-type ATPases and the ATP-sensitive potassium channel. Overall, through this ambitious program of research, we plan to shed new light on membrane protein complexes and the role of lipids and small molecules in stabilising and modifying their properties.

Keywords: mass spectrometry integral membrane proteins gas phase activation molecular arichitecutre of portein complexes
Metabolic consequences of mitochondrial dysfunction (METABOMIT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Finland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

This proposal aims to clarify mitochondrial contribution to obesity and thinness, using carefully characterized mitochondrial disease and obese patient materials, and genetically modified disease models. Manifestations of mitochondrial respiratory chain (RC) defects range from infantile multisystem disorders to adult-onset myopathies or neurodegeneration, and even aging-related wasting. Why defects in oxidative ATP production can lead to such variety of manifestations and tissue specificity is unknown. We have previously identified a number of gene defects that lead to RC disorders. In addition to neurological symptoms, these patients often show various metabolic manifestations: specific gene defects associate with short stature and thinness, whereas others with metabolic syndrome or obesity. This implies that specific mitochondrial defects can have opposing effects for fat storage or utilization. The involved pathways may contribute to mitochondrial disease progression, but are unknown. We propose to a) undertake a major clinical study on genetically defined, obese or thin, mitochondrial patients, and examine their metabolic phenotype in finest detail. These data will be compared to those from normal obesity, to search for common mechanisms between mitochondrial and general obesity. b) generate a set of disease models for mitochondrial disorders associated with obesity, and knock-out models for specific signallers for crossing with the disease models. c) identify in detail the involved regulatory pathways, and utilize these for searching chemical compounds that could modulate the response, and have therapeutic potential. The project has potential for major breakthroughs in the fields of mitochondrial disease pathogenesis and treatment, neurodegeneration and obesity.

Keywords: biological basis of obesity,mitochondrial disorders,biological basis of neurodegeneration
Developing maximum-resolution genotype-phenotype maps using whole-genome polymorphism data (MAXMAP)

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: Austria
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2183956.0
EU funding (EUR): 2183956.0
Participants: 1
Project status: CLOSED

Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases, genome-wide association studies (GWAS) have, owing to advances in genotyping and sequencing technology, become an obvious general approach for studying the genetics of natural variation. They are particularly useful when inbred lines are available because once these lines have been genotyped they can be phenotyped multiple times, making it possible (as well as extremely cost-effective) to study many different traits in many different environments, while replicating the phenotypic measurements to reduce environmental noise. Here we propose to continue our groundbreaking GWAS work in the model plant Arabidopsis thaliana. We will explore the limits of the approach, moving beyond marker-trait linkage disequilibrium to full sequence information. We will carry out GWAS of important life-history traits using over 1000 inbred A. thaliana lines for which nearly complete sequence information is available. The GWAS will be complemented by linkage mapping in F2 crosses to eliminate confounding linkage disequilibrium, associations will be verified experimentally, and confirmed causal polymorphisms will be added to the model in an iterative manner in order to create an increasingly refined genotype-phenotype map.
Lymphocyte microRNAs in health and disease: Understanding lymphocyte functions through the identification of microRNA target genes and exploiting serum microRNA signatures to monitor immune responses (I-MIRNOME)

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: Italy
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2496000.0
EU funding (EUR): 2496000.0
Participants: 2
Project status: CLOSED

Background: CD4+ T lymphocyte subsets orchestrate immune responses in health and disease. Little is known on control of T cell differentiation exerted by microRNA that affect mRNA translation. The identification of microRNA and their targets that regulate differentiation of T cell subsets may provide new therapeutic targets for immune-mediated diseases. Since microRNA are released in exosomes and circulate in blood, activities of tissue-derived lymphocytes could be assessed by microRNA signatures in the serum. We have defined microRNAs present in resting lymphocyte subsets from peripheral blood and measured lymphocyte-derived microRNAs in the serum. We have also solved important challenges for the identification of microRNA targets, the definition of signatures of activated T cells and their monitoring in the serum, which form the key topics of this application. Advancing State-of-the-Art and objectives: We will identify microRNA of CD4+ T cell subsets purified from inflamed organs and investigate microRNA target network that regulates T cell differentiation. We will exploit this knowledge to profile signatures of in vivo activated T cells and to map genes that could improve understanding of T cell commitment. We will also develop quantitative assays to monitor microRNA signatures in the serum and provide functional evidence of key genes targeted by microRNA which could be targets of immunomodulatory drugs. Significance: This application addresses important challenges at the frontiers of immunology and could lead to significant advances in immunotherapies and diagnostic tools for patients with immune mediated diseases. New ways of identifying microRNA targets and techniques to quantify microRNA signatures in the serum, could be widely applicable in biomedical research.

Keywords: microrna,biomarkers
Impact of identified interneurons on cellular network mechanisms in the human and rodent neocortex (INTERIMPACT)

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: Hungary
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2017-05-31
Duration (months): 72.0
Total project cost (EUR): 2391694.8
EU funding (EUR): 2391694.8
Participants: 1
Project status: CLOSED

This application addresses mechanisms linking the activity of single neurons with network events by defining the function of identified cell types in the cerebral cortex. The key hypotheses emerged from our experiments and propose that neurogliaform cells and axo-axonic cells achieve their function in the cortex through extreme forms of unspecificity and specificity, respectively. The project capitalizes on our discovery that neurogliaform cells reach GABAA and GABAB receptors on target cells through unitary volume transmission going beyond the classical theory which states that single cortical neurons act in or around synaptic junctions. We propose that the spatial unspecificity of neurotransmitter action leads to unprecedented functional capabilities for a single neuron simultaneously acting on neuronal, glial and vascular components of the surrounding area allowing neurogliaform cells to synchronize metabolic demand and supply in microcircuits. In contrast, axo-axonic cells represent extreme spatial specificity in the brain: terminals of axo-axonic cells exclusively target the axon initial segment of pyramidal neurons. Axo-axonic cells were considered as the most potent inhibitory neurons of the cortex. However, our experiments suggested that axo-axonic cells can be the most powerful excitatory neurons known to date by triggering complex network events. Our unprecedented recordings in the human cortex show that axo-axonic cells are crucial in activating functional assemblies which were implicated in higher order cognitive representations. We aim to define interactions between active cortical networks and axo-axonic cell triggered assemblies with an emphasis on mechanisms modulated by neurogliaform cells and commonly prescribed drugs.

Keywords: gaba,interneuron,nonsynaptic,cortex,human,rodent
Predicting extinction risk in declining species: The role of behavioral and ecological traits (VULNERABILITY TRAITS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2010-03-01
End date: 2012-02-29
Duration (months): 24.0
Total project cost (EUR): 156002.68
EU funding (EUR): 156002.68
Participants: 1
Project status: CLOSED

Understanding and predicting the response of animal populations to anthropogenic activity is a major challenge in biodiversity conservation. Species are not equally affected by habitat loss and degradation. However, our current understanding of what makes some species more vulnerable than others is fragmentary, and we have limited tools to use that information for the management and assessment of imperiled populations. Identifying life history, ecological, and behavioral (LEB) traits associated with vulnerability could significantly improve conservation efforts by prioritizing research and encouraging proactive actions. Similarly, generating population models that explicitly consider these key traits and their interactions will strengthen our ability to assess and manage populations at risk. This study will address both of these needs. First, we will conduct a comprehensive comparative study of the families Felidae, Canidae, and Ursidae to reveal the relationship between widespread LEB traits, demography and vulnerability. These families are an ideal surrogate group to address this question because they are well-studied (with many spatial and temporal replicate studies) and encompass a diversity of vulnerability statuses, threats, and life histories. Secondly, we will identify functional relationships, interactions and trade-offs between key LEB traits and demographic parameters. Finally, we will integrate these functional relationships into LEB-explicit models. Anticipated results will advance conservation theory and practice in several ways. Understanding common vulnerability traits will encourage more effective and proactive management, and could help prioritize research by focusing the initial collection of data on the key traits. Defining functional relationships and generating LEB-explicit models will provide great insight into life history patterns and trait interaction, and improve our ability to predict wildlife responses to anthropogenic activities.

Keywords: biodiversity indicators,risk assessment,causes and mechanisms of loss,carnivores,mammals
Development of sol-gel inkjet inks for printing on glass substrates for architectural applications (TIGJET)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Austria
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2009-04-10
End date: 2011-04-09
Duration (months): 24.0
Total project cost (EUR): 168577.15
EU funding (EUR): 168577.15
Participants: 1
Project status: CLOSED

Industrial sol-gel inkjet inks for printing on glass substrates for architectural applications should be developed. There is a strong worldwide market demand for individual custom made decorative glass surfaces for exterior architectural applications. One of the main challenges today in the glass industry is the adhesion and exterior durability of coatings and printings on glass. The only fully commercial route today available is screen printing inorganic inks resulting in a very limited colour range and high application cost. Inkjet printing would be an ideal technology achieving economic and flexible custom made designs. However, today inkjet printing is mainly used in graphic arts applications with limited durability. First inkjet applications using ceramic inks made out of fine grinded frits and inorganic pigments appeared on the market but seem to be inferior, difficult to use, limited in color space, print quality and very limited in ink stability. Two different routes of inkjet printing on glass should be evaluated. Specialized stable sol-gel inkjet inks with superior adhesion to glass and excellent exterior durability should be developed in close cooperation with a major inkjet printer manufacturer and an applicator. Route 1: Stable inorganic-organic hybrid inks compositions based on low-temperature UV curable silanes allowing incorporation of organic and inorganic pigments should be developed. Superior adhesion to glass and exterior durability are the main features of printings on the basis of these inks. Route 2. Purely inorganic water based stable sol-gel inkjet inks compositions based on silica, titania, alumina or mixtures of above, as matrix forming agents with inorganic pigments as colour agents shall be developed. Special attention will be paid to the development of sol-gel inks that produce colour on thermal treatment of prints, avoiding issues arising during pigments stabilization in the compositions as well as printheads blocking.

Keywords: inkjet,sol-gel,inorganic glass coating,organic glass coating,uv curing,architectural glass,tempered glass coating,custom matched design
CHARACTERISATION OF ARKADIA FUNCTION IN THE REGULATION OF SNON STABILITY AND ITS ROLE AS A POTENTIAL TUMOUR SUPPRESSOR (ARKADIA AND CANCER)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2010-03-01
End date: 2012-02-29
Duration (months): 24.0
Total project cost (EUR): 172434.64
EU funding (EUR): 172434.64
Participants: 1
Project status: CLOSED

Deregulated signalling by transforming growth factor beta (TGF-beta) plays a critical role in tumorigenesis in humans, acting as a tumour suppressor at early stages, but as a tumour promoter at late stages. To be able to diagnose and treat human cancer, it is essential that we understand these processes at the molecular level. Recent work in the host lab has established that the E3 ubiquitin ligase, Arkadia is an essential component of the branch of the TGF-beta/Smad pathway that is mediated via activated Smad3/Smad4 complexes. The lab has shown that Arkadia functions by targeting the transcriptional repressors, SnoN and Ski for degradation by the proteasome in response to TGF-beta signalling. Loss of Arkadia results in the stabilisation of SnoN and loss of Smad3/Smad4-dependent transcription, two events that are hall marks of some human tumours. Moreover, the host lab has identified an adenocarcinoma cell line, SEG-1, that expresses a non-functional truncated Arkadia protein due to a point mutation. Consequently these cells are deficient in TGF-beta-induced SnoN degradation. Taken together, these results suggest that Arkadia might be a novel tumour suppressor. The first aim of my proposal is to elucidate the mechanism whereby Arkadia mediates TGF-beta-induced SnoN degradation. For this I will take a biochemical and structural approach and will also use siRNA sceening to identify what other components are required. I will also address what genes are regulated by Arkadia by microarray analysis. The second aim is to determine the role of Arkadia in tumorigenesis. I will focus on assessing the effect of restoring Arkadia expression in SEG-1 cells on cell growth and migration in vitro and on tumour growth and metastasis in mouse models. I will also screen for loss of Arkadia expression in human tumour cell lines and tumours to discover whether Arakdia is a novel tumour suppressor gene that is targeted in human cancer.

Keywords: cancer,e3 ubiquitin ligases,arkadia,tgf-beta,smad,ski and snon,tumour suppressor
Metal catalysed C–H bond activation strategies for chemical synthesis & cancer biology (CHACT_RHAZ)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2009-04-06
End date: 2011-04-05
Duration (months): 24.0
Total project cost (EUR): 182484.78
EU funding (EUR): 182484.78
Participants: 1
Project status: CLOSED

Chemical synthesis relies on the presence of functional groups to control the formation of new bonds. The area of catalytic C–H bond functionalisation offers a pioneering opportunity to develop highly efficient, ‘green’ and new chemical transformation that will be pivotal in the future development of chemical synthesis. While we are not suggesting that this approach will replace the conventional tactics of molecule assembly it does offer the synthetic chemist the chance to explore completely unknown strategies. More specifically, it allows us to put the standard rulebook of disconnections to one side and invent a new set of reactions that allow us to break down a molecule without needing to locate a functional group in the synthons. Breaking a C–C, C–N or C–O bond back to a number of C–H bonds represents the pinnacle of modern synthetic chemistry. To achieve this would allow metal catalysed C–H bond functionalisation strategies to offer a conceptually new approach to synthesis that will compliment conventional synthesis and enable us to move a step closer to being able to assemble any desired molecule. As part of this proposal we aim to develop a metal catalyzed C–H bond functionalization strategy that will enable the rapid and flexible synthesis of the intriguing tubulin destabilizing agent, rhazinilam. Furthermore, we will also investigate a totally unprecedented natural product re-arrangement strategy that enables the facile conversion of the rhazinilam framework into the aspidospermidine framework. This rearrangement blueprint, that the Host group name ‘retro-biosynthesis’ as it goes against the proposed classical biosynthetetic pathway, provides immediate access to a family of compounds (the vinca alkaloids) that have potent biological activities in cancer medicine.

Keywords: organic chemistry,carbon chemistry,homogeneous catalysis