Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Development of an accessible platform for ex vivo site specific post-translational modifications of proteins (PROTLEGO)

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: Israel
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2016-03-31
Duration (months): 66.0
Total project cost (EUR): 1398000.0
EU funding (EUR): 1398000.0
Participants: 1
Project status: CLOSED

The incorporation of unnatural amino acids (more than 50 to date) into proteins in vivo has resulted in the generation of proteins with novel chemical, biological, and physical properties. However, some unnatural amino acids possess properties, such as an inability to cross the cell membrane or a level of toxicity dangerous to the organism, that restrict their incorporation into proteins in vivo. In addition, even when an unnatural amino acid crosses the cell membrane, its transport efficiency within the cell is very low. We propose to overcome these limitations by exploiting translational components evolved tRNA-synthetases and their cognate suppressor-tRNA from Archea for the incorporation of an array of unnatural amino acids into proteins in vitro in a cell-free protein translation system. The expressed recombinant proteins containing the unnatural amino acids will be purified from the reaction mixture and used for further research. Using the cell free system, first we will demonstrate our new approach by incorporating novel unnatural amino acids, i.e., thiolysine analogues, into proteins using the broad substrate specificity of evolved tRNA synthetases. We will then incorporate a thiolysine analogue into PCNA for the site-specific ubiquitination and SUMOylation of these proteins for in vitro studies of the interactions between PCNA and interacting proteins and to follow the progress of the replication fork. This unique approach will show for the first time the use of evolved synthetases in a cell free translation system, with the advantage being that previously un-incorporable unnatural amino acids can be incorporated using this approach. Our overall aim is to enable the introduction of new functionalities into proteins.

Keywords: unnatural amino acids,cell free translation,pcna,ubiquitin,thiolysine,sumo
Investigating the role of pre-synaptic HCN1 channels in regulating cortical synaptic transmission and plasticity. (IRPHRCSTP)

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-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2016-11-30
Duration (months): 72.0
Total project cost (EUR): 1400547.0
EU funding (EUR): 1400547.0
Participants: 1
Project status: CLOSED

Voltage-gated ion channels are important determinants of neuronal excitability. The Hyperpolarization-activated Cation Non-selective (HCN) channels are voltage-gated ion channels that open with hyperpolarization at subthreshold potentials. Four subtypes (HCN1-4) have been cloned. There is considerable interest in HCN1 channels as they have been shown to have roles in physiological processes such as learning and memory as well as pathophysiological conditions such as epilepsy. Many studies have shown that they are highly localised to hippocampal and cortical cell pyramidal cell dendrites. Interestingly, emerging immunohistochemical evidence suggests that they may also be present in axons and synaptic terminals. In support of this, our recent work shows that excitatory synaptic transmission is significantly enhanced in the entorhinal cortex (EC) in HCN1 null mice, suggesting that HCN1 channels may play a role in regulating neurotransmitter release. In the proposed work, we wish to test the hypothesis that HCN1 channels exist at glutamatergic synaptic terminals in the EC, where they regulate synaptic transmission. We also wish to investigate the cellular mechanisms by which pre-synaptic HCN1 channels may influence synaptic release. Finally, we wish to explore the physiological function of these pre-synaptic HCN1 channels. To address these questions, we will use a multi-disciplinary approach involving conventional electrophysiology, state-of-the art multi-photon microscopy imaging and electron microscopy coupled with transgenic mice and pharmacology. The results produced will have significant ramifications not only in the field of ion channels, particularly HCN channels, and neuron excitability but also for understanding the factors involved in controlling neurotransmission, synaptic strength and ultimately neural network excitability.

Keywords: ion channels,neuronal excitability,hcn channels,synaptic release,neurotransmission
Quantitative Analysis of the Hourglass Model of Evolution of Development. (HOURGLASS)

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: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-09-01
End date: 2016-02-29
Duration (months): 66.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

The observation that different species within one animal phylum resemble one another in the course of embryonic development fascinated scientists since the dawn of developmental biology. Already in 1828, Carl Ernst von Baer formulated his third law of embryonic development, later extended into the hourglass model that recognizes the phylotypic stage during mid-embryogenesis as the most constrained period of development, preceded and followed by greater morphological divergence. The arguments for the existence of the developmental hourglass come primarily from comparative morphological analysis of vertebrate embryos and are, to the large extent, qualitative. This proposal describes experiments designed to test the hourglass model quantitatively using sequenced Drosophila species as a model system. The approach is unique, because by focusing on a set of highly similar species, it will be possible to precisely quantify the differences among them and use statistical and genetic modeling approaches to evaluate the hourglass hypothesis. The divergence of genome expression and embryo morphology will be evaluated before, during and after the phylotypic stage, using deep sequencing and high-resolution microscopy combined with advanced image analysis. The two sets of measurements will be linked through cross-species, reverse genetic manipulation of the genomes, attempting to establish a causal chain of events from sequence divergence, through divergence in gene expression patterns to the divergent phenotype of the embryo. The quantitative analysis of the developmental hourglass will provide conclusive evidence for or against the existence of the constraints in gene regulatory networks underlying the phylotypic stage and shed light on one of the most fundamental laws in biology.

Keywords: biological image analysis,in toto imaging of biological systems,selective plane illumination microscopy,deep sequencing
Why do we do what we do? Biological, psychological and computational bases of motivation (BIOMOTIV)

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: France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-03-01
End date: 2016-08-31
Duration (months): 66.0
Total project cost (EUR): 1346000.0
EU funding (EUR): 1346000.0
Participants: 1
Project status: CLOSED

We are largely unaware of our own motives. Understanding our motives can be reduced to knowing how we form goals and these goals translate into behavior. Goals can be defined as pleasurable situations that we particularly value and that we intend to reach. Recent investigation in the emerging field of neuro-economics has put forward a neuronal network constituting a brain valuation system (BVS). We wish to build a more comprehensive account of motivational processes, investigating not only valuation and choice but also effort (how much energy we would spend to attain a goal). More specifically, our aims are to better describe 1) how the brain assigns values to various objects and actions, 2) how values depend on parameters such as reward magnitude, probability, delay and cost, 3) how values are affected by social contexts, 4) how values are modified through learning and 5) how values influence the brain systems (perceptual, cognitive and motor) that underpin behavioral performance. To these aims, we would combine three approaches: 1) human cognitive neuroscience, which is central as we ultimately wish to understand ourselves, as well as human pathological conditions where motivation is either deficient (apathy) or out of control (compulsion), 2) primate neurophysiology, which is essential to describe information processing at the single-unit level and to derive causality by observing behavioral consequences of brain manipulations, 3) computational modeling, which is mandatory to link quantitatively the different descriptions levels (single-unit recordings, local field potentials, regional BOLD signal, vegetative manifestations and motor outputs). A bayesian framework will be developed to infer from experimental measures the subjects prior beliefs and value functions. We believe that our team, bringing together three complementary perspectives on motivation within a clinical environment, would represent a unique education and research center in Europe.

Keywords: reward,decision-making,learning,fmri,electrophysiology,pharmacology,deep brain stimulation,bayesian theory,basal ganglia,dopamine,noradrenalin
Roles of non-coding RNAs in viral infections in mammals (NCRNAVIR)

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: France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1471620.0
EU funding (EUR): 1471620.0
Participants: 1
Project status: CLOSED

The importance of small non-coding RNAs is growing exponentially in modern biology. They have recently emerged as critical regulators of gene expression. Different classes of small RNAs have been defined, and among them micro (mi) RNAs, and small interfering (si) RNAs are the most studied. Viruses interact extensively with the RNA silencing machinery. Thus in plants and insects, they are directly targeted and degraded by Dicer proteins. The situation is more complicated in mammals, where a more sophisticated innate immune response has replaced this antiviral mechanism. Nevertheless, there are interactions between viruses and mammalian RNA silencing pathways, which mainly involve miRNAs. On one hand, miRNAs of cellular origin can regulate viral RNAs, and on the other hand, some viruses have evolved to express their own miRNAs. This project aims at characterizing the full scope of interactions between mammalian viruses and the RNA silencing machinery. Using both RNA and DNA viruses, we will identify cellular miRNAs that have antiviral or proviral properties, and correlate these finding with the changes in cellular miRNA profiles induced by viral infection. We will set apart the mechanisms by which a given cellular miRNA has anti or proviral activity, and the counter methods that viruses could deploy to prevent their targeting. The second part of the project pertains to the study of viral miRNAs, and we will elucidate their roles both during in vitro and in vivo infection; we will also analyze how their expression is regulated. Finally, the last part of the project will consist in deciphering how viruses affect the RNA silencing machinery. This will entitle the characterization of RNA silencing complexes composition and subcellular localization during viral infection.

Keywords: microrna,rna silencing,rna virus,herpesvirus,posttranscriptional modifications
Management of Hypotension In the Preterm Extremely Low Gestational Age Newborn (THE HIP TRIAL)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Collaborative project
Countries involved: Ireland,Belgium,Czechia,Canada,Ireland,France,United Kingdom,Germany,France,Belgium,Czechia,Czechia
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-10-01
End date: 2017-09-30
Duration (months): 84.0
Total project cost (EUR): 6951616.44
EU funding (EUR): 5355322.25
Participants: 17
Project status: CLOSED

Assuming an annual birth rate of 10.25 births/1,000 population approximately 25,000 Extremely Low Gestational Age Newborns are born every year in the EU. Conservative figures estimate that approximately half of all these babies will develop low blood pressure and require treatment. However, no uniform criteria exist to define hypotension and the evidence to support our current management strategies is limited. Many of these interventions have been derived from adult literature and have not been validated in the newborn. Dopamine remains the most common inotrope used despite little evidence that it improves outcome. Hypotension is not only associated with mortality of preterm infants but is also associated with brain injury and impaired neurosensory development in ELGAN survivors. Preterm brain injury has far reaching implications for the child, parents, family, health service and society at large. It is therefore essential that we now design and perform the appropriate trials to determine whether the infusion of inotropic agents is associated with improved outcome. We have assembled a consortium with expertise in key areas of neonatal cardiology, neonatology, neurophysiology, basic science and pharmacology with the intention of answering these questions. The objectives of the group are as follows: 1. To perform a multinational, randomized controlled trial to evaluate whether a more restricted approach to the diagnosis and management of hypotension compared to a standard approach, with dopamine as a first line inotrope, affects survival without significant brain injury at 36 weeks gestational age in infants born less than 28 weeks gestation and affects survival without neurodevelopmental disability at 2 years corrected age 2. To perform pharmacokinetic and pharmcodynamic studies of dopamine 3. To develop and adapt a formulation of dopamine suitable for newborns in order to apply for a Paediatric Use Marketing Authorization

Keywords: blood pressure,extremely low gestational age newborns,hypotension,dopamine,epinephrine,multinational,randomized,controlled,clinical trial,puma,preterm newborn,elgan,inotrope,nirs,eeg
Unveiling the Roles of Chromatin Insulators in Higher-order Chromatin Architecture and Transcription Regulation one molecule at a time. (SMINSULATOR)

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-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Eukaryotic chromosomes are condensed into several hierarchical levels of complexity: DNA is wrapped around core histones to form nucleosomes, nucleosomes form a higher-order structure called chromatin, and chromatin is subsequently organized by long-range contacts. The conformation of chromatin at these three levels greatly influences DNA transcription. One class of chromatin regulatory proteins called insulator factors set up boundaries between heterochromatin and euchromatin and generate long-range loops. In Drosophila, three types of insulators (Su(Hw), dCTCF and BEAF) have been shown to regulate transcription and organize chromatin at the higher level by the formation of long-range interactions that were proposed to be mediated by the coalescence of several insulator proteins into clusters (insulator bodies). Our research aims to unravel the mechanism by which insulator bodies dynamically regulate chromatin structure and transcription by using single-molecule biophysics and quantitative modeling. On one hand, we will apply novel super-resolution fluorescence microscopy methods to investigate the structure and assembly dynamics of insulator bodies in single cells throughout the cell cycle and the role of their regulatory partners. On the other hand, we will reconstitute the looping activity of insulators in vitro and apply single-molecule manipulation methods to gain detailed insights into the molecular mechanisms involved in defining and regulating chromatin organization by insulators. This project has the potential to impact our understanding of several fundamental cellular processes: transcription regulation, cell-cycle dynamics, higher-order chromatin organization, and cell differentiation. The methods developed here will be directly applicable to the investigation of other nuclear super-structures, such as transcription and replication factories and Polycomb bodies, and thus will impact other research areas, such as DNA replication, transcription and cell division.

Keywords: single-molecule biophysics,long-range chromatin loops,insulator elements
Drug addiction: molecular changes in reward and aversion circuits (ADDICTIONCIRCUITS)

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: Sweden
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2015-09-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Our affective and motivational state is important for our decisions, actions and quality of life. Many pathological conditions affect this state. For example, addictive drugs are hyperactivating the reward system and trigger a strong motivation for continued drug intake, whereas many somatic and psychiatric diseases lead to an aversive state, characterized by loss of motivation. I will study specific neural circuits and mechanisms underlying reward and aversion, and how pathological signaling in these systems can trigger relapse in drug addiction. Given the important role of the dopaminergic neurons in the midbrain for many aspects of reward signaling, I will study how synaptic plasticity in these cells, and in their target neurons in the striatum, contribute to relapse in drug seeking. I will also study the circuits underlying aversion. Little is known about these circuits, but my hypothesis is that an important component of aversion is signaled by a specific neuronal population in the brainstem parabrachial nucleus, projecting to the central amygdala. We will test this hypothesis and also determine how this aversion circuit contributes to the persistence of addiction and to relapse. To dissect this complicated system, I am developing new genetic methods for manipulating and visualizing specific functional circuits in the mouse brain. My unique combination of state-of-the-art competence in transgenics and cutting edge knowledge in the anatomy and functional organization of the circuits behind reward and aversion should allow me to decode these systems, linking discrete circuits to behavior. Collectively, the results will indicate how signals encoding aversion and reward are integrated to control addictive behavior and they may identify novel avenues for treatment of drug addiction as well as aversion-related symptoms affecting patients with chronic inflammatory conditions and cancer.

Keywords: reward,aversion,relapse,addiction,transgenic
Host and viral factors in acute hepatitis C (HEPACUTE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Germany,France,Germany,Germany,Italy,Spain,Switzerland,United Kingdom,United Kingdom,Egypt,Germany,Morocco
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-11-01
End date: 2014-04-30
Duration (months): 42.0
Total project cost (EUR): 3854861.4
EU funding (EUR): 2999500.0
Participants: 17
Project status: CLOSED

Chronic hepatitis C is one of the most common chronic viral infections of humans and a major cause of chronic liver disease, cirrhosis and liver cancer. Still about 4 million new infections occur world-wide each year with 50-85% of patients progressing to chronic hepatitis C. Currently there is no marker to predict spontaneous viral clearance and to guide treatment decisions. The major objectives of the HepaCute proposal are to develop biomarkers predicting the outcome of acute hepatitis C, improving the management of the related patients and thus decreasing the health burden of hepatitis C in Europe and Mediterranean partner countries (MPC). The HepaCute consortium has evolved from a series of EC-funded projects on hepatitis C (HCVacc/HepCvax/Virgil/HEPACIVAC) and consists of world leading experts in HCV epidemiology, immunology, and virology, including partners from Egypt and Morocco, who have strongly influenced the current management of patients with acute hepatitis C in their respective regions, and contributed considerably to our understanding of mechanisms of spontaneous viral clearance. The HepaCute proposal is closely connected to ongoing national, European, and Egyptian networks on HCV research (HepNet, EASL, STDF), which will support HepaCute to make it a success.Together with another pertinent EU-funded research project, SPHINX, it actively contributes to coordinating EU-funded hepatitis C research with pertinent research projects funded in the MCP countries, in particular with hepatitis research projects funded under the Egyptian Science and Technology Development Fund (STDF). Within HepaCute the most innovative technologies will be employed such as genome-wide association studies, transcriptomics, proteomics, and ultra-deep sequencing to better understand the early events in acute hepatitis C and to translate these results into readily practicable diagnostic tools to predict spontaneous viral clearance. HepaCute has firmly integrated partners from Egypt and Morocco with preexisting research collaborations with European partners into the scientific research programm and we expect this continuing partnership between European and Mediterranean countries to have a strong impact on the care of patients with acute hepatitis C both in Europe and MPC.