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 TERMINÉ 
"Transcriptional regulation of protein coding genes in eukaryotic cells requires a complex interplay of sequence-specific DNA-binding factors, co-activators, general transcription factors (GTFs), RNA polymerase II and the epigenetic status of target sequences. Nuclear transcription complexes function as large multiprotein assemblies and are often composed of functional modules. The regulated decis ...
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 1

 TERMINÉ 
Neuropathic pain has a high incidence in Europe and often affects the patient’s emotional balance and quality of life. Recent meta-analyses have shown that conventional analgesic drugs are not sufficiently effective in these patients and are limited by serious side effects. The search for new analgesics is extremely difficult despite identification of several new potential targets and enormous inv ...
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 12

 TERMINÉ 
"Chronic pain is prevalent and it causes decreased quality of life and significant costs to the society in terms of lost working capacity. Currently available analgesics are either not effective enough or patients cannot take them due to adverse effects. Non-steroidal anti-inflammatory drugs are a major cause of drug-related morbidity and mortality. Opioids can cause tolerance and addiction when u ...
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 5

 TERMINÉ 

REGULATION OF TRANSCRIPTION (REGTRANS)

Date du début: 1 avr. 2014, Date de fin: 31 mars 2018,

"During the first step of gene expression, RNA Polymerase (RNAP) transcribes RNA from a DNA template in every living cell. Crystal structures of RNAP core as well as RNAP elongation complexes (ECs) have revolutionized our understanding of transcription. This groundwork paved the way for more complex questions addressing the regulation of transcription. Because of its fundamental role, transcriptio ...
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 1

 TERMINÉ 

UNDERSTANDING THE CAUSES OF THE RNA GAIN OF FUNCTION DISEASES (RNA DISEASES)

Date du début: 1 mars 2013, Date de fin: 28 févr. 2018,

"It is now increasingly clear that most of our genome is transcribed, but that only a small portion is associated with protein coding gene. Indeed, recent analysis indicate that long non-coding RNA outnumbered by five fold the coding RNA sequences. Despite this abundance, very little is known on the function of these long non-coding RNA.The aim of this proposal is to understand the function of pat ...
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 1

 TERMINÉ 

Pluripotent stem cell resources for mesodermal medicine (PLURIMES)

Date du début: 1 févr. 2014, Date de fin: 31 janv. 2018,

Harnessing the capacity of pluripotent stem cells (PSCs) to produce functional cell types with precision and at scale will enable new treatment modalities for degenerative diseases. A major target for such therapies is mesodermal tissue, muscle, bone and cartilage. The goal of PluriMes is to create a bioengineering platform for directing PSCs into specific classes of mesodermal/mesenchymal progeni ...
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 12

 TERMINÉ 

Nuclear foundations of cellular potency (NUCLEARPOTENCY)

Date du début: 1 févr. 2012, Date de fin: 31 janv. 2018,

A fundamental question in biology is to understand the mechanisms underlying cell plasticity. Such plasticity or potency is essential to form multiple cell types upon differentiation. In mammals, upon fertilization and fusion of the gametes –two highly differentiated cells- intense chromatin remodeling and epigenetic reprogramming, the reversion into an undifferentiated state, are essential to res ...
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 2

 TERMINÉ 

Control of metabolic and inflammatory pathways by nuclear receptors (NR-NET)

Date du début: 1 sept. 2013, Date de fin: 31 août 2017,

NR-NET is a multidisciplinary consortium, whose activities are directed towards the understanding of the role of Nuclear Receptors (NRs) and coregulators in metaflammatory disease. Metaflammation - metabolic disorders linked to chronic inflammation – is an emerging concept explaining the pathogenesis of a wide-spectrum of diseases. Since several nuclear receptors can directly sense metabolic alter ...
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 11

 TERMINÉ 
The importance of mechanical forces in biology is well accepted, yet an integrated view of their mode of action in vivo is lacking. We intend to characterize in-depth the physical forces and cellular processes that coordinate the morphogenesis of different cell types contributing to an organ, taking the C. elegans embryo as a paradigm.We will achieve this by pursuing three axes:1. Building on our ...
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 2

 TERMINÉ 

Structural Basis of Protein Synthesis System of Human Cell (SBPSSHS)

Date du début: 1 avr. 2012, Date de fin: 31 mars 2017,

"This project will elucidate the structure and mechanism of ribosome function through the determination of high resolution crystal structures of human ribosome functional complexes. Currently, the only high resolution crystal structures available for the ribosome functional complexes are bacterial ribosomes containing mRNA, tRNAs in E, P and A sites and several translation factors. Recently, we ha ...
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 1

 TERMINÉ 
"Protein kinases represent key signal transduction components transferring signals to their effectors by phosphorylation. Among other important functions, MAPK-dependent signal transduction is principally required to control inflammation and metabolism in vertebrates. However, chronic MAPK signaling in response to environmental stress contributes to the development of metabolic and inflammatory di ...
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 1

 TERMINÉ 

Anti-Parasitic Drug Discovery in Epigenetics (A-PARADDISE)

Date du début: 1 févr. 2014, Date de fin: 31 janv. 2017,

This proposal builds on the proven methodology developed in the SEtTReND FP7 project to develop inhibitors of schistosome HME as lead compounds for new drugs. We will employ a target-based strategy for the development of novel drug leads against schistosomiasis, leishmaniasis, Chagas disease and malaria by targeting histone modifying enzymes (HME), in particular those involved in acetylation/deace ...
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 16

 TERMINÉ 

SYSTEMS BIOLOGY OF PATHWAYS INVOLVING BRAIN AGEING (AGEDBRAINSYSBIO)

Date du début: 1 janv. 2013, Date de fin: 31 déc. 2016,

In spite of valuable approaches applied to get a broad understanding of genetic, epidemiologic and molecular and system-level biological principles of human aging, cognitive decline remains as one of the greatest health challenges of the old age, with nearly 50% of adults over 85 afflicted of Alzheimer’s disease. Furthermore, drug development has not performed as expected in clinical trials, at le ...
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 15

 TERMINÉ 
The mouse shows great similarities in development, physiology and biochemistry to humans, which makes it a key model for research into human disease. The major challenges for mouse functional genomics in the 21st century are to:• Develop a series of mutant alleles for every gene in the mouse genome• Determine the phenotypic consequences of each mutation• Identify mouse models for the complete dise ...
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 24

 TERMINÉ 
DNA is tightly wrapped around histones to form chromatin, a highly dynamic structure that can adopt different conformations with contrasting degrees of compaction. Essential processes of DNA metabolism, such as DNA repair, replication or transcription operate in the context of chromatin and higher order chromosomal organization. Understanding how modulation of chromatin structure and repair influe ...
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 10

 TERMINÉ 

European Medicines Research Training Network (EMTRAIN)

Date du début: 1 oct. 2009, Date de fin: 30 sept. 2016,

EMTRAIN is an essential element for the success of the IMI Education & Training (E&T) Call Topics in Europe (current and future). It will establish a pan-European platform of excellence for education and training covering the whole life-cycle of medicines from basic research through clinical development to pharmaco-vigilance. It will underpin the successful delivery of the current and future IMI-f ...
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 32

 TERMINÉ 

Epigenetics towards systems biology (EPIGENESYS)

Date du début: 1 oct. 2010, Date de fin: 31 mars 2016,

The ‘EpiGeneSys’ Network of Excellence aims to enable European epigenetics research to enter the arena of systems biology, a new step forward with major implications for human health. Many diseases, not explained solely by gene mutation, have rather been associated with epigenetic disorders. Following the identification of key epigenetic regulators, a move towards a systems biology approach is nee ...
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 28

 TERMINÉ 

Sarcomere based Signals in Muscle Remodelling (SARCOSI)

Date du début: 1 avr. 2012, Date de fin: 31 mars 2016,

The sarcomere is the structural unit of striated muscle tissues where thick and thin filaments cooperate to achieve muscle contraction. Recently it is becoming increasingly clear that sarcomeres have in addition to muscle contraction also important signaling functions: Stretch and strain sensing signalosomes are assembled by the giant muscle proteins titin and nebulin, that in turn are embedded in ...
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 14

 TERMINÉ 
In hematopoiesis, failure to maintain homeostasis and regenerative functions result in a multitude of hematological malignancies, including myelodysplastic syndromes, lymphomas and leukemias, that represent a medical challenge and a large socioeconomic burden because of the large number of affected patients of all age groups. Although hierarchical organization of the hematopoietic system has been ...
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 12

 TERMINÉ 

EUCOMM: Tools for Functional Annotation of the Mouse Genome (EUCOMMTOOLS)

Date du début: 1 oct. 2010, Date de fin: 30 sept. 2015,

The EUCOMMTOOLS Collaborative Project responds to the topic ‘HEALTH.2010.2.1.1-1: Large-scale efforts in mouse functional genomics to determine the functions of genes and their involvement in disease.’ EUCOMMTOOLS will provide, in a systematic high-throughput way, genetic tools and resources contributing to the determination of every gene’s function in any cell type of the entire organism at any g ...
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 11

 TERMINÉ 
Double-strand breaks (DSBs) occur frequently in the genome by DNA damaging agents or during genome replication. DSBs are hazardous because interaction between DNA ends from different double strand breaks can produce tumorigenic chromosome translocations. Little is known about how repair factors function in the context of chromatin and how translocations form in vivo. I developed a cell system in w ...
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 1

 TERMINÉ 
Cell proliferation, differentiation and death are controlled by different transcription factors amongst which the non-steroid nuclear receptors (nsNR). Deciphering the mechanisms of action of nsNR is a challenge in various research fields ranging from cancer and neurodegenerative disorders to metabolic diseases. According to the canonical signalling pathway liganded nsNR, in the form of dimers wit ...
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 1

 TERMINÉ 

Genetic and Epigenetic Networks in Cognitive Dysfunction (GENCODYS)

Date du début: 1 mai 2010, Date de fin: 30 avr. 2015,

Mutations in about 400 different genes have been associated with Cognitive Disorders (CD), such as mental retardation, autism, neurodegenerative disorders, and psychiatric disorders. Whereas CD impose a major medical and socio-economical problem, there are no systematic studies that aim to provide insight into common mechanisms in CD. We propose a systems biology approach to gain insight into comm ...
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 15

 TERMINÉ 

European Friedreich's Ataxia Consortium for Translational Studies (EFACTS)

Date du début: 1 mai 2010, Date de fin: 30 avr. 2015,

EFACTS (the European Friedreich’s Ataxia Consortium for Translational Studies) assembles a body of expertise to adopt a translational research strategy for the rare autosomal recessive neurological disease, Friedreich’s ataxia (FRDA). FRDA is a severely debilitating disease that leads to loss of the ability to walk and dependency for all activities. Some patients have cardiomyopathy that can cause ...
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 15

 TERMINÉ 

Building The Vertebrate Body (BODYBUILT)

Date du début: 1 avr. 2010, Date de fin: 31 mars 2015,

"My lab is interested in the development of the tissue that gives rise to vertebrae and skeletal muscles called the paraxial mesoderm. A striking feature of this tissue is its segmental organization and we have made major contributions to the understanding of the molecular control of the segmentation process. We identified a molecular oscillator associated to the rhythmic production of somites and ...
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 1

 TERMINÉ 
InfraCoMP will establish efficient coordination mechanisms between the ESFRI project Infrafrontier and the International Mouse Phenotyping Consortium. Infrafrontier is a pan-European initative to build a sustainable research infrastructure for systemic phenotyping, archiving and distribution of mouse models of human diseases. The IMPC is a global project to carry out systemic phenotyping of mouse ...
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 9

 TERMINÉ 

Dynamics and stability of covalent protein modifications (PROTMOD)

Date du début: 1 sept. 2008, Date de fin: 31 août 2014,

"One of the major goals of post-genomic biological research is to understand the molecular basis and physiological role of covalent protein modifications. Post-transcriptional modifications can regulate protein interactions and/or stability and thus trigger particular downstream responses. A major challenge is to understand how modifications of histone proteins are translated into changes in gene ...
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 3

 TERMINÉ 

Biological flows and embryonic development (Flowbuilt)

Date du début: 1 juil. 2010, Date de fin: 30 juin 2014,

Embryonic development is a highly controlled process where biochemical networks are constantly challenged by environmental cues. In a growing embryo, cells grow, divide, migrate, differentiate or arrange to form structures in a mechanically active environment where they can physically alter their environment and react to these changes. It is unclear how do biological systems sense their physical e ...
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 1

 TERMINÉ 

TFIIH as a crucial actor in genome expression and repair (TransReAct)

Date du début: 1 janv. 2009, Date de fin: 31 déc. 2013,

Understanding how the genetic information of a cell is retrieved but also protected from insults, is a major challenge facing modern molecular biology. Indeed, one of the most important developments in human genetics over the last decade, has been the realization that diseases such as cancer but also ageing stem from some dis-regulation in the expression and preservation of the genetic information ...
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 1

 TERMINÉ 
Chromatin packages a few meters of DNA into a nucleus measuring a few microns. This tight folding occurs by assembling DNA with histones into so-called nucleosomes, thus ensuring the mechanical stability of our genome. On the flipside, this makes nucleosomes a formidable obstacle to the machines that read, copy or repair its DNA message. One of the fundamental questions in biology is to understand ...
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 17

 TERMINÉ 

Prostate Research Organizations-Network of Early Stage Training (PRO-NEST)

Date du début: 1 oct. 2009, Date de fin: 30 sept. 2013,

"New and recent developments have revolutionized the prostate cancer research and clinical arenas, requiring the next generation scientists to have comprehensive knowledge and expertise in basic, clinical and applied research. PRO-NEST offers young researchers a European integrated, multi-disciplinary training programme to become an independent and all-round scientist and team leader in (prostate) ...
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 18

 TERMINÉ 
"The project aims at unraveling the molecular pathophysiology of recessive ataxias, a heterogeneous set of severely disabling neurodegenerative disorders due to loss of function of proteins involved either in mitochondrial/metabolic pathways or DNA repair. Friedreich ataxia, the most common form, is due to partial loss of function of frataxin, a mitochondrial protein involved in iron-sulfur cluste ...
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 1

 TERMINÉ 
Histone acetyltransferases (HATs) play a critical role in regulating gene expression of many cellular functions. Interestingly, the vision of histones being unique substrates for different HATs has recently changed, since HATs can also regulate essential functions such as protein turnover or cell cycle progression, via acetylation of non-histone proteins. HATs and their acetylation activity must h ...
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 1

 TERMINÉ 

Schistosoma Epigenetics - Targets, Regulation, New Drugs (SEtTReND)

Date du début: 1 janv. 2010, Date de fin: 31 déc. 2012,

We propose to develop novel drug leads for the therapy of the major human parasitic disease, schistosomiasis, using a holistic approach that will enable us to progress from the cloned target protein to the lead compound and from epigenetic inhibitors to crucial targets. For this, we have chosen to target the histone modifying enzymes (HME); histone deacetylases (HDAC), histone acetyltransferases ( ...
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 9

 TERMINÉ 
Cancer is one of the major causes of mortality. Epithelial cells become malignant after accumulating genetic mutations followed by morphological changes in the epithelium. DNA Alterations include stable genetic changes in oncogenes, tumor suppressor genes and reversible epigenetic changes. Different forms of epigenetic mechanisms have been shown to modify the expression of key genes during tumour ...
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 7

 TERMINÉ 
"Deciphering the complexity of chromatin-encoded information is the prerequisite for understanding the regulatory circuits governing development and (patho)physiology. Transcription factors and epigenetic modulators translate chromatin-embedded information in a dynamic and cell/gene context specific manner to orchestrate homeostasis, growth and differentiation. To date, the most powerful and commo ...
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 11

 TERMINÉ 

European Consortium for Systematic Stem Cell Biology (EUROSYSTEM)

Date du début: 1 mars 2008, Date de fin: 31 août 2012,

EuroSyStem brings together elite European research teams to create a unique and world-leading programme in fundamental stem cell biology. By interconnecting complementary biological and computational expertise we will drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. We will pave the way for application of systems methodology by measuring and modelling ...
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 25

 TERMINÉ 
"The cardiovascular system is vital to every vertebrate and is the first functional organ in the developing embryo. As a consequence, the heartbeats generate hemodynamic forces that physically stimulate growing arteries and veins at the earliest steps of cardiovascular development. The mechanisms involved in vascular morphogenesis are poorly understood. One of the fundamental questions is whether ...
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 1

 TERMINÉ 
Type II DNA topoisomerases (topoII) control DNA topology during replication, transcription and chromosome segregation. Essential for cell proliferation, topoII are targets of antibacterial and antineoplasic compounds of prime importance for human health. The emergence of antibiotic resistant bacterial strains and the selection of resistance clones during cancer treatment urge for the development o ...
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 1

 TERMINÉ 
"This proposal describes CREATE, an internationally based Coordination Action directly addressing a large scale data gathering activity for systematic conditional mouse mutagenesis. Advances in the sophisticated manipulation of the mouse genome has established the mouse as the premier organism for developing models of human disease. Internationally coordinated initiatives have established for the ...
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 8