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 TERMINÉ 

INtestinal Tissue ENgineering Solution (INTENS)

Date du début: 1 janv. 2016, Date de fin: 31 déc. 2020,

Short Bowel Syndrome (SBS) is a condition that occurs when part or the entire small intestine is missing or has been removed during surgery. This condition renders the bowel incapable of fulfilling its nutritional function (intestinal failure). There is no cure for SBS. Parenteral (intravenous) nutrition (PN) and bowel transplantation are currently the preferred options for nutrition in children a ...
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 9

 TERMINÉ 

Reconstitution of Chromosome Replication and Epigenetic Inheritance (CHROMOREP)

Date du début: 1 nov. 2015, Date de fin: 31 oct. 2020,

A PubMed search for ‘epigenetic’ identifies nearly 35,000 entries, yet the molecular mechanisms by which chromatin modification and gene expression patterns are actually inherited during chromosome replication — mechanisms which lie at the heart of epigenetic inheritance of gene expression — are still largely uncharacterised. Understanding these mechanisms would be greatly aided if we could reco ...
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 1

 TERMINÉ 

Functions of the X chromosome in the mammalian germ line (XChromosome)

Date du début: 1 nov. 2015, Date de fin: 31 oct. 2020,

Male and female mammals differ in their sex chromosome complement: males have one X chromosome and one Y chromosome (XY), while females have two X chromosomes (XX). Decades of research have demonstrated that the Y chromosome is crucial for male fertility, regulating both sex differentiation and spermatogenesis. However, the role of the X chromosome in these critical stages of germ line development ...
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 1

 TERMINÉ 

Establishment of Sister Chromatid Cohesion (ChromatidCohesion)

Date du début: 1 oct. 2015, Date de fin: 30 sept. 2020,

Following their synthesis during DNA replication, sister chromatids remain paired by the cohesin complex, which forms the basis for their faithful segregation during cell division. Cohesin is a large ring-shaped protein complex, incorporating an ABC-type ATPase module. Despite its importance for genome stability, the molecular mechanism of cohesin action remains as intriguing as it remains poorly ...
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 1

 TERMINÉ 

DNA strand break repair and links to human disease (DNA2REPAIR)

Date du début: 1 sept. 2015, Date de fin: 31 août 2020,

Our genetic material is continually subjected to damage, either from endogenous sources such as reactive oxygen species, produced as by-products of oxidative metabolism, from the breakdown of replication forks during cell growth, or by agents in the environment such as ionising radiation or carcinogenic chemicals. To cope with DNA damage, cells employ elaborate and effective repair processes that ...
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 1

 TERMINÉ 
MicroRNAs (miRNAs) can be transferred between cells, representing an exciting new dimension to intercellular communication, referred to as non-cell-autonomous gene regulation. We recently identified that distinct miRNAs are packaged and exported from TREG cells and delivered directly to TH1 cells, suppressing T cell-mediated disease. Different T cell populations express different miRNAs and releas ...
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 1

 TERMINÉ 
The cell is the universal unit of living matter, and there cannot be propagation of life without cell division. DivIDe aims to investigate the mechanisms and principles of cell division and to reproduce them in vitro with synthetic approaches. Crucial to cell division is the mitotic spindle, a structure whose main duty is the separation of chromosomes. The spindle is made of microtubules (MT), mol ...
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 9

 TERMINÉ 
The ability of cells to polarize underlies the most basic biological functions such as motility and response to external challenges, but also the formation and maintenance of tissues in a multicellular organism. The importance of cell polarity is underscored by the fact that cell polarity is essential for animal development and is perturbed in disease states such as cancer. Understanding cell pola ...
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 9

 TERMINÉ 

Tumour Heterogeneity and Somatic Evolution of Unstable cancer genomes (THESEUS)

Date du début: 1 juin 2014, Date de fin: 31 mai 2019,

SummaryThe majority of metastastic solid tumours remain incurable. In-depth analysis of tumour genomes is revealing evidence for branched evolution and cancer subclonal spatial and temporal intratumour heterogeneity (ITH). Drivers of ITH such as chromosomal instability (CIN) are associated with drug resistance and poor clinical outcome. However, despite increasing knowledge of tumour diversity, th ...
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 3

 TERMINÉ 

RNA-based technologies for single-cell metabolite analysis (MetaRNA)

Date du début: 1 janv. 2015, Date de fin: 31 déc. 2018,

Metabolism is the foundation of all living organisms. While cells in a population are often phenotypically different, most of our current analytical approaches still probe metabolism only at the population level. Because strong evidence exists that metabolic cell-to-cell heterogeneity has, for instance, disease relevance, researcher from MetaRNA will overcome this severe analytical limitation thro ...
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 11

 TERMINÉ 

Development and Characterisation of New Immunogenic GEMMs of Lung Cancer (iGEMMdev)

Date du début: 1 janv. 2017, Date de fin: 31 déc. 2018,

Many studies have recently archived a remarkable clinical efficacy of immunotherapeutic treatments in several cancers including non-small cell lung cancer (NSCLC). However, these approaches are not always successful and it is currently impossible to predict a therapeutic response or serious adverse event. These fundamental issues need to be addressed and, to recapitulate the complexity of interact ...
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 1

 TERMINÉ 
...tions by cementing a sustainable science, technology and innovation network with two internationally-leading organisations in the immunity and infection area of research, the Institut Pasteur and the Francis Crick Institute. The strategy of TwinnToInfect, based on science- and innovation-driven clustering, is focused on this societal challenge that lies at the centre of many age-related disorders. ...
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 3

 TERMINÉ 

Strategies towards Excellence in Immuno-Oncology (STREAM)

Date du début: 1 janv. 2016, Date de fin: 31 déc. 2018,

In 2013, the Science magazine announced Immunotherapy of cancer as the ‘Breakthrough of the Year’. The results of ongoing clinical studies with new cancer immunotherapeutics strongly support this enthusiasm. Following the lead of the top research groups, the Coordinator of the present proposal, Medical University of Warsaw (MUW) displays a predominant ambition of becoming a major player in the thr ...
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 7

 TERMINÉ 

Characterization of RTEL1 mutations in Hoyeraal-Hreidarsson Syndrome (RTEL1inHHS)

Date du début: 1 janv. 2017, Date de fin: 31 déc. 2018,

Hoyeraal-Hreidarsson syndrome (HHS) is a multisystem disorder with patients presenting inter-uterine growth retardation, immunodeficiency, and/or aplastic anaemia. Recently, mutations in RTEL1 have been shown to be causal for this disease. RTEL1 prevents genomic instability and maintains integrity of the telomeres by disassembling different secondary structures that arise during DNA replication, r ...
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 1

 TERMINÉ 
Malaria is one of the most devastating infectious diseases affecting half of the world population and killing close to a million people every year. Widespread resistance of the malaria parasite to most front-line drugs and the rapid emergence of resistance against new therapies have made the validation of novel pharmaceutical targets and the identification of potent pharmacophores extremely urgent ...
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 2

 TERMINÉ 
This proposal addresses the call topic ‘Advancing bioinformatics to meet biomedical and clinical needs’ (PHC-32-2014), with the focus on the standardization, dissemination and meta-analysis of cell migration data. Cell migration is the fundamental process in medically highly relevant topics, including morphogenesis, immune function, wound healing, and cancer metastasis, and the study of cell migra ...
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 10

 TERMINÉ 
Owing to advances in sequencing technology, we are now beginning to understand the molecular mechanisms underlying cancer development and evolution. Tumours however are heterogeneous, often containing admixed normal cells and different (sub)clones, confounding interpretation of the massive amounts of data flowing from large initiatives such as the International Cancer Genome Consortium.To address ...
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 1

 TERMINÉ 
Protein fatty-acylations (N-myristoylation, S-palmitoylation and Lys-fatty acylation) are important lipid-modifications that regulate the trafficking and function of membrane-associated proteins in eukaryotes. With the development of new chemical proteomic methods by the Hang laboratory and others, many additional protein candidates of fatty-acylation have been reported. Notably, the Hang group ha ...
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 1

 TERMINÉ 
The microtubule cytoskeleton provides an intracellular coordinate system and a mechanical scaffold for a multitude of essential cellular functions. The design principles underlying the dynamic organisation and function of the microtubule cytoskeleton are not understood. Using an in vitro reconstitution approach, we will determine the rules that govern which combination of mechano-chemical elements ...
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 2

 TERMINÉ 

Targeting RAS oncogene addiction (RASTARGET)

Date du début: 1 mai 2013, Date de fin: 30 avr. 2018,

Lung cancer is the most common type of malignant tumour worldwide and the leading cause of cancer-related death (335,000 deaths per year in Europe). The KRAS oncogene is frequently activated by point mutation in human lung cancer and mutations in the RAS family oncogenes are responsible for driving some 20% of all human malignancies. Most cell lines from RAS mutant tumours remain “oncogene addicte ...
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 2

 TERMINÉ 
Recent live cell imaging studies have demonstrated that cancer cells invade either as single cell or as cell group retaining cell-cell adhesion. In contrast to the well-documented single cell movement, little is known about collective cancer cell invasion. Given that a single tumour tissue contains various types of cancer cells and the collective movement of cancer cells is sum of the behavior of ...
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 1

 TERMINÉ 
ATM is the protein kinase that is mutated in the hereditary autosomal recessive disease ataxia telangiectasia (A-T). A-T patients display immune deficiencies, cancer predisposition and radiosensitivity. The molecular role of ATM is to respond to DNA damage by phosphorylating its substrates, thereby promoting repair of damage or arresting the cell cycle. Following the induction of double-strand bre ...
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 2

 TERMINÉ 
Aneuploidy, an abnormal number of chromosomes, is a hallmark of cancer cells, affecting the majority of all human tumours. Aneuploidy arises when errors occur during mitosis, as the duplicated chromosomes are distributed between the two new daughter cells. Paradoxically, aneuploidy appears to have detrimental consequences for the physiology of untransformed cells in vitro, inhibiting rather than s ...
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 14

 TERMINÉ 

MAL: an actin-regulated SRF transcriptional coactivator (ACTINONSRF)

Date du début: 1 oct. 2011, Date de fin: 30 sept. 2017,

MAL: an actin-regulated SRF transcriptional coactivatorRecent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-bindi ...
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 2

 TERMINÉ 

European Initial Training Network on Developmental and Computational Biology (DevCom)

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

The ability to manipulate cellular pluripotency and differentiation holds the as yet unrealized promise of regenerative medicine to produce replacement cells and tissues. To this end a deep understanding of the regulation of differentiation potential in the context of normal embryonic development is crucial. The recent revolution in sequencing technology has enabled high throughput and genome-wide ...
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 8

 TERMINÉ 
Dendritic cells (DC) are a heterogeneous family of leucocytes with important functions in immunity. Little is known about the role of distinct DC subtypes in vivo. In the mouse, a subset known as CD8alpha+ DC has been argued to represent a discrete DC lineage with specialised properties. These include a superior capacity for presenting exogenous antigens to CD8+ and CD4+ T cells, which makes CD8al ...
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 2

 TERMINÉ 
It is estimated that more than 200 million Europeans suffer from at least one type of allergy. This condition is elicited by an hyper-activated type-2 inflammatory response coordinated by T helper (TH)-2 cells. In spite a good insight into the molecular mechanisms that triggers TH2 cells activation, the lack in understanding their post-transcriptional regulation is hampering the access to new pote ...
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 2

 TERMINÉ 

Investigating eukaryotic replisome dynamics at the single molecule level (SMI REP)

Date du début: 1 août 2015, Date de fin: 31 juil. 2017,

For cells to reproduce, an accurate duplicate of the genome must be created. This is no small task. The genetic information stored in each cell consists of ~6 billion pairs of nucleobases (base pairs, bp) assembled as a polymer 2 metres long and 2 nanometres in diameter, with the structural form of a double helix. For a mammalian cell to divide, this deoxyribonucleic acid (DNA) must be copied in a ...
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 2

 TERMINÉ 
Wnts are signaling proteins that act both at short and long range in developing tissues. Several proteins, such as Wntless, are specifically devoted to Wnt secretion, indicating that Wnts may follow a distinct secretory route. Moreover, Wnts carry two lipid modifications, which are likely to interfere with diffusion in the extracellular space. Much of our work will focus on the trafficking of Wing ...
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 2

 TERMINÉ 
Homologous recombination (HR) is an essential DNA repair mechanism and defects in different HR factors are linked with disease and cancer pre-disposition. The RAD51 recombinase plays a central role in HR, forming nucleoprotein filaments at sites of DNA damage and promoting homologous pairing and DNA strand exchange. RAD51 filament formation is mediated by the BRCA2 tumour suppressor, mutations in ...
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 2

 TERMINÉ 
3' untranslated regions (3' UTRs) serve as a key platform in the RNA regulatory network that controls mRNA translational efficiency, localisation and stability. Of all human cell-types, brain-specific isoforms have the longest 3' UTRs and therefore their regulation is likely to be most complex. Moreover, mutations perturbing the mRNA secondary structure and sites of mRNA-miRNA interactions can lea ...
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 2

 TERMINÉ 
Malaria is a devastating disease caused by the apicomplexan parasite Plasmodium. Plasmodium falciparum represents the most severe and life-threatening form of human malaria, causing over 500,000 deaths per year. There is no efficient vaccine available and resistance to all currently used drugs reported. One of the major problems in eradicating human malaria is the transmission of the parasites sex ...
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 2

 TERMINÉ 
I initiated and developed an unbiased comprehensive study using whole genome array analysis of the transcriptome in blood of tuberculosis (TB) patients and provided global knowledge of the immune response and potential factors leading to TB pathogenesis. Using larger cohorts of TB patients and controls than previous studies, together with complementary analytical approaches of modular, pathway and ...
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 2

 TERMINÉ 
Morphogens are locally produced molecules that act over long distances in tissues to control the pattern of gene expression. A particularly well-understood model system for studying the mechanisms of morphogen-mediated patterning is the vertebrate neural tube. Here, Sonic Hedgehog (Shh) induces discrete neuronal progenitor domains through regulation of a combinatorial code of transcription factors ...
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 2

 TERMINÉ 

The interplay between innate immunity and RNA interference in mammals (RNAi vs IFN)

Date du début: 1 mars 2015, Date de fin: 28 févr. 2017,

In antiviral RNAi, the DICER (DCR) enzyme processes virus-derived double-stranded (ds)RNA into siRNAs that guide ARGONAUTE proteins to silence complementary viral RNA. As a counter-defense, viruses deploy viral suppressors of RNAi (VSRs). Well-established in plants and invertebrates, the existence of antiviral RNAi in mammals has remained unknown until our recent findings (from my first postdoctor ...
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 2

 TERMINÉ 

Molecular basis of IGF2BPs-mediated lncRNAs degradation (LNCRNATURNOVER)

Date du début: 1 sept. 2014, Date de fin: 30 sept. 2016,

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) constitute a conserved family of oncofetal RNA binding proteins (RBPs) important in embryonic development, and whose expression in tumours is strongly correlated to cancer dissemination. There are three isoforms in mammals, IGF2BP1-3, which regulate mRNA transport, translation, and RNA stability, in a RNA target-dependent manner. Recentl ...
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 2

 TERMINÉ 

Anatomy and dynamics of the human replisome (AnDyHRep)

Date du début: 1 sept. 2014, Date de fin: 31 août 2016,

Accurately copying its whole genome is perhaps the most important task of the cell. Mistakes in DNA replication can result in cell death or, potentially worse, in mutagenesis and genomic instability, which in turn can lead to uncontrolled proliferation, the basis of cancer. Elucidating the factors involved in DNA replication and understanding the mechanisms by which human cells guarantee the prec ...
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 2

 TERMINÉ 

Transcription and the maintenance of genome integrity (TRANSINTEG)

Date du début: 1 mai 2011, Date de fin: 30 avr. 2016,

Maintaining genome integrity is crucial, especially in protein-encoding genes. DNA damage in genes can give rise to harmful mutations, but it can also directly obstruct the progress of transcribing RNA polymerase II (RNAPII), thereby blocking gene expression. Not surprisingly, repair pathways have evolved that specifically target lesions that stop RNAPII during its journey across a gene, so-called ...
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 2

 TERMINÉ 

Regulating recombination in mitotic and meiotic cells (RECMITMEI)

Date du début: 1 mai 2011, Date de fin: 30 avr. 2016,

DNA is a highly reactive molecule that is subject to deliberate, spontaneous and environmental damage. One of the most catastrophic lesions in DNA is the double-strand break (DSB), which if left unrepaired can result in cell death, infertility, genome instability and cancer. Homologous recombination (HR) is a largely error-free mechanism of DSB repair that utilizes an intact sister or homologous c ...
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 2

 TERMINÉ 

Role of nuclear architecture in cancer development (ACTINNUCLSHAPECANCER)

Date du début: 1 avr. 2014, Date de fin: 31 mars 2016,

Nuclear shape is one of the gold standards for detection and characterization of cancers. Nonetheless the control of nuclear morphology and its relationship to malignant behaviors are still poorly understood. We propose to study the mechanisms that lead to nuclear dysmorphia and their consequence on nuclear functions such as genome integrity and migration. The first part of the research will start ...
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 2