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 TERMINÉ 

Biomechanics and signaling in models of congenital heart valve defects (EVALVE)

Date du début: 1 déc. 2016, Date de fin: 30 nov. 2021,

Mechanical forces are fundamental to cardiovascular development and physiology. The interactions between mechanical forces and endothelial cells are mediated by mechanotransduction feedback loops. My lab is interested in understanding how hemodynamic forces modulate cardiovascular function and morphogenesis. Overall, our recent work is unraveling the biological links between mechanical forces, mec ...
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 1

 TERMINÉ 

Understanding and manipulating the dynamics of chromosome topologies in transcriptional control (CHROMTOPOLOGY)

Date du début: 1 juin 2016, Date de fin: 31 mai 2021,

Transcriptional regulation of genes in eukaryotic cells requires a complex and highly regulated interplay of chromatin environment, epigenetic status of target sequences and several different transcription factors. Eukaryotic genomes are tightly packaged within nuclei, yet must be accessible for transcription, replication and repair. A striking correlation exists between chromatin topology and und ...
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 1

 TERMINÉ 

Structural and biochemical studies on the regulation of transcription during elongation (TRANSREG)

Date du début: 1 juin 2016, Date de fin: 31 mai 2021,

During the first step of gene expression, a universally conserved enzyme called RNA Polymerase (RNAP) transcribes RNA from a DNA template in every cell. Transcription is a fundamental, yet incompletely understood process. Because of its central role, the bacterial transcription machinery is also a prime drug target. Crystal structures of RNAP core as well as RNAP elongation complexes (ECs) have re ...
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 1

 TERMINÉ 

Generation of the CanPath prototype - a platform for predictive cancer pathway modeling (CanPathPro)

Date du début: 1 mars 2016, Date de fin: 28 févr. 2021,

Recent developments in omics technologies demand implementation of systems biology approaches to facilitate analysis and interpretation of the generated complex datasets.This is essential for biotechnological as well as preclinical and clinical applications. In comparison to previous approaches, most cancer relevant studies are confined to pattern recognition or at best modelling of single pathway ...
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 9

 TERMINÉ 

Molecule-to-man pain network (PAIN-Net)

Date du début: 1 févr. 2017, Date de fin: 31 janv. 2021,

Neuropathic pain affects 5% of the general population and 40% of patients with neurological diseases, and has a key role in the pathophysiology of cancer pain that affects up to 50% of patients in the early disease stage and 30% of survivors, causing an enormous social burden. Treatments are inadequate with less than 50% of patients achieving 50% of pain relief at best, while up to 30% of cancer p ...
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 13

 TERMINÉ 

Towards enduring mouse resources and services advancing research into human health and disease (INFRAFRONTIER2020)

Date du début: 1 janv. 2017, Date de fin: 31 déc. 2020,

The INFRAFRONTIER RI integrates European Mouse Clinics and the European Mouse Mutant Archive with the common goal to ensure access to mouse models for basic research of human health and disease, and to translate this knowledge into therapeutic approaches for the benefit of the European society. The expanded INFRAFRONTIER2020 network, coordinated by the INFRAFRONTIER GmbH, includes 3 SMEs and is st ...
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 33

 TERMINÉ 

4D analysis of heart development and regeneration using advanced light microscopy (4DHeart)

Date du début: 1 janv. 2017, Date de fin: 31 déc. 2020,

Cardiovascular (CV) disease is a main cause of death worldwide. During adulthood, ischemic heart disease leads to heart failure and perinatally, congenital heart defects are found in over 20% of deaths. Moreover, genetic or epigenetic factors altering development can have an impact much later in life. These facts underscore the need of a better understanding of the genetic and environmental factor ...
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 7

 TERMINÉ 

Unraveling Principles of PDZ-mediated Cell Signaling (PDZnet)

Date du début: 1 sept. 2016, Date de fin: 31 août 2020,

PDZnet will create an innovative European PhD training network focusing on unraveling PDZ domain-mediated signaling networks. The emphasis will be on signaling nodes essential for the development of cancer and diseases of the nervous system, conditions that affect millions of Europeans and are major societal challenges. PDZ domains are protein and lipid recognizing modules that play a central role ...
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 10

 TERMINÉ 

Using a natural cellular plasticity event to decypher the cellular requirements and molecular circuitry promoting transdifferentiation at the single cell level. (PlastiCell)

Date du début: 1 juil. 2015, Date de fin: 30 juin 2020,

How differentiated cells can change their identity is a fascinating question. Indeed, natural interconversions between functionally distinct somatic cell types (aka transdifferentiation, Td) have been reported in species as diverse as jellyfish and mice, while experimentally induced reprogramming of differentiated cells has been demonstrated. The relative ease with which cellular identities can be ...
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 1

 TERMINÉ 

Deciphering PI3K biology in health and disease (Phd)

Date du début: 1 nov. 2015, Date de fin: 31 oct. 2019,

The Phosphoinositide 3-kinase (PI3K) pathway is at the core of multiple fundamental biological processes controlling metabolism, protein synthesis, cell growth, survival, and migration. This inevitably leads to the involvement of the PI3K signalling pathway in a number of different diseases, ranging from inflammation and diabetes to cancer, with PI3K pathway alterations present in almost 80% of hu ...
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 11

 TERMINÉ 

Research Infrastructures for Phenotyping, Archiving and Distribution of Mouse Disease Models - Promoting International Cooperation and User Engagement to Enhance Biomedical Innovation (IPAD-MD)

Date du début: 1 juin 2015, Date de fin: 31 mai 2019,

The IPAD-MD project addresses cooperation and coordination between the pan-European INFRAFRONTIER Research Infrastructure and complementary research infrastructures in America, Asia and Australia, contributing to the global effort of the International Mouse Phenotyping Consortium (IMPC). In order to increase the reach of INFRAFRONTIER, IPAD-MD will also reach out to complementary infrastructures a ...
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 11

 TERMINÉ 

“Quantitative analysis of the molecular and cellular behaviors associated with cardiac valve morphogenesis in pathological and regenerative contexts” (ZEBRA-VALVE)

Date du début: 1 févr. 2017, Date de fin: 31 janv. 2019,

Cardiovascular diseases (CVDs) take a huge toll on the world population. An estimated 19 million people died from CVDs in 2010, representing 30% of all global deaths. Abnormal blood circulation is widely recognized as a cardiovascular risk factor and mechanotransduction has been shown to trigger pathologies such as atherosclerosis1, cardiomyopathies2 and valvulopathies3. Mechanotransduction is the ...
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 1

 TERMINÉ 

From birth to action: regulation of gene expression through transcription complex biogenesis (BIRTOACTION)

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

"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: biomarkers and druggable targets within the endogenous analgesia system (NEUROPAIN)

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

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 

Understanding chronic pain and new druggable targets: Focus on glial-opioid receptor interface (GLORIA)

Date du début: 1 nov. 2013, Date de fin: 31 oct. 2018,

"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 input of mechanical forces to morphogenesis and wound healing: a systematic dissection (MORPHORCE)

Date du début: 1 mai 2012, Date de fin: 30 avr. 2017,

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 

Stress signaling mechanisms in metabolism and inflammation and related disorders (STRESSMETABOL)

Date du début: 1 févr. 2012, Date de fin: 31 janv. 2017,

"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 

Development of mouse mutant resources for functional analyses of human diseases - Enhancing the translation of research into innovation (INFRAFRONTIER-I3)

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

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 

Joint training and research network on Chromatin Dynamics and the DNA Damage Response (ADDRESS)

Date du début: 1 oct. 2012, Date de fin: 30 sept. 2016,

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 

HEMatopoietic cell IDentity : genetic and epigenetic regulation in normal and malignant hematopoiesis (HEM_ID)

Date du début: 1 nov. 2011, Date de fin: 31 oct. 2015,

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 

Nuclear architecture in DNA repair and formation of chromosomal translocatons (NADRCT)

Date du début: 1 juil. 2011, Date de fin: 30 juin 2015,

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 

Genetische Mechanismen kardiovaskulärer Erkrankungen (Mécanismes génétiques maladies cardio-vasculaires)

Date du début: 30 juin 2012, Date de fin: 29 juin 2015,

Les maladies cardio-vasculaires (MCV) et leurs complications sont une des causes principales de mortalité chez lhomme. Ce projet consiste à développer des approches fonctionnelles, afin de définir précisément limpact de plusieurs variants génétiques associés à ces MCV. La meilleure connaissance des gènes liés aux MCV et de leurs mécanismes daction permettrait de développer des approches de prévent ...
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 7

 TERMINÉ 

Non-canonical signalling pathways relayed by retinoic acid affecting germ cell differentiation (InVivo_RA_NonCanon)

Date du début: 1 mars 2013, Date de fin: 20 juin 2015,

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 

Integrative structure and function study of the bacterial and human protein synthesis machinery (TRANSLATIONMACHINERY)

Date du début: 1 déc. 2009, Date de fin: 30 nov. 2014,

"The aim of the project is to understand key steps in the molecular mechanisms of protein synthesis across species. The structure and function of pro- and eukaryotic (including human) ribosomes, those cellular nano-machineries that catalyse the decoding of genes, will be studied through an integrative, interdisciplinary structural biology approach. Since in the cell the ribosome is regulated by tr ...
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 1

 TERMINÉ 

Coordinating the cooperation of the ESFRI project Infrafrontier with the International Phenotyping Consortium (IMPC) (INFRACOMP)

Date du début: 1 oct. 2011, Date de fin: 30 sept. 2014,

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