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 TERMINÉ 

Design Principles of Microtubule Cytoskeleton Architectures during Cell Division (SPINDLEDESIGN)

Date du début: 1 juil. 2013, Date de fin: 30 juin 2018,

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 

ATMINistrating ATM signalling: exploring the significance of ATM regulation by ATMIN (ATMINDDR)

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

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 

The impact of chromosomal instability on health: Molecular causes and consequences of aneuploidy (PLOIDYNET)

Date du début: 1 oct. 2013, Date de fin: 30 sept. 2017,

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 

Cross-species characterisation of CD8alpha+ dendritic cells and their role in immune regulation (DCSUBSET)

Date du début: 1 sept. 2011, Date de fin: 31 août 2017,

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 

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 

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 

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 

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 

Structural and biochemical characterization of the BRCA2 breast cancer tumour suppressor (BRCA2complexes)

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

Our genetic material is constantly exposed to mutagenic factors. DNA double-strand breaks (DSBs) represent one of the most dangerous forms of DNA damage and cells utilise two major pathways for their repair: error-prone non-homologous end-joining (NHEJ) and error-free homologous recombination (HR). The breast cancer susceptibility protein BRCA2 is a central player in HR that cooperates with its pa ...
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 1

 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

 TERMINÉ 

Asymmetrical B cell division: origin and functional significance (ASYMMETRY IN B CELLS)

Date du début: 1 janv. 2014, Date de fin: 31 déc. 2015,

B cell activation required for antibody production and the establishment of immunological memory is initiated by antigen recognition through the B cell receptor (BCR) and subsequent internalization of antigen for presentation to T cells. After activation, B cells proliferate and differentiate into plasma cells or memory B cells. The mechanism involved in this B cell fate decision has been recently ...
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 2

 TERMINÉ 

Generation of a new class of antiretrovirals targeting HIV-cellular cofactors interactions (HIVINNOV)

Date du début: 1 oct. 2012, Date de fin: 30 sept. 2015,

Highly active antiretroviral therapy is effective at controlling HIV-1 replication, however emergence and transmission of drug-resistant viruses is increasing, including viruses resistant to the newly developped integrase catalytic inhibitors. It is essential that new antiretrovirals (ARVs) become available. Most ARVs in development belong to the classes of viral enzyme inhibitors. Since HIV requi ...
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 7

 TERMINÉ 

Single cell level intravital imaging of response, tolerance, and resistance to targeted therapies (ImageMelTherapyLRI)

Date du début: 1 juil. 2013, Date de fin: 30 juin 2015,

Oncogenic signalling by kinases presents a significant opportunity for cancer therapy. The B-Raf selective inhibitor, Vemurafenib, has shown great effect against B-Raf mutant melanoma patients. However, drug resistance emerges in nearly every case. Various mechanisms underlying this resistance are described, however these approaches usually overlook the heterogeneity of the tumour microenvironment ...
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 2

 TERMINÉ 

Telomere function in meiosis (TELOMERES IN MEIOSIS)

Date du début: 1 juin 2010, Date de fin: 31 mai 2015,

Telomeres have long been known to play crucial roles in protecting chromosome ends from attrition and fusion and thus safeguarding genome stability, but their complete functional repertoire has yet to be fully understood. Among the fundamental roles of telomeres is their role in meiosis, the process by which parental genomes are recombined and halved, allowing the generation of genetic diversity v ...
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 1

 TERMINÉ 

Defects in DNA strand break repair and links to inheritable disease (DNAREPAIR)

Date du début: 1 juin 2010, Date de fin: 31 mai 2015,

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 s ...
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 2

 TERMINÉ 

In vitro reconstitution of the replication machinery on a chromatin template (DNA replication)

Date du début: 1 juin 2013, Date de fin: 31 mai 2015,

DNA replication, the process where the genetic material is duplicated, is one of the most important and basic processes a cell undertakes. It is essential that this process is tightly and carefully regulated as errors in DNA replication are catastrophic, resulting in diseases like cancer. The synthetic or S phase of the eukaryotic cell cycle is entirely devoted to genome duplication by orchestrati ...
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 2

 TERMINÉ 

The dendritic cell receptor DNGR-1: Modulation of endosomal dynamics upon recognition of necrotic cells (DNGR-1 in DCs)

Date du début: 1 mai 2013, Date de fin: 30 avr. 2015,

Dendritic cells (DCs) play an essential function in initiating adaptive immunity. Key to DC function are receptors for recognizing and capturing pathogens and damaged cells and for controlling subsequent antigen extraction, processing and presentation. DNGR-1 (also known as CLEC9A) is a DC-restricted C-type lectin receptor (CLR) that recognizes the actin cytoskeleton exposed on necrotic cells. DNG ...
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 2

 TERMINÉ 

The Initiation of Eukaryotic DNA Replication: Mechanism, Regulation and Role in Genome Stability (EUKDNAREP)

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

In each cell cycle, eukaryotic cells must faithfully replicate large genomes in a relatively short time. This is accomplished by initiating DNA replication from many replication origins distributed along chromosomes. Ensuring that each origin is efficiently activated once and only once per cell cycle is crucial for maintaining the integrity of the genome. Recent evidence indicates that defects in ...
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 2

 TERMINÉ 

Mechanism of Holliday junction dissolution by the Bloom’s Syndrome complex (BLMCOMPLEX)

Date du début: 1 mai 2013, Date de fin: 30 avr. 2015,

Our genetic material is continually subjected to damage and efficient repair is needed for cancer avoidance. DNA double-strand breaks are cytotoxic and are repaired either by Non Homologous End-Joining or Homologous Recombination (HR). HR provides an important function in DNA repair, where it serves the dual purpose of mending broken chromosomes and recovering sequence information that might be l ...
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 2

 TERMINÉ 

Regulation of the Hippo tissue growth pathway by nutrient sensing mechanisms in Drosophila melanogaster (HippoGailite)

Date du début: 1 avr. 2013, Date de fin: 31 mars 2015,

The Hippo pathway is a highly conserved tumour suppressor pathway that restricts cell proliferation and promotes apoptosis. Although initially discovered in Drosophila, the Hippo pathway is highly conserved in mammals. Mutations and epigenetic silencing of Hippo pathway genes are frequently found in cancer tissues. Thus, our understanding of pathway regulation is important for the understanding of ...
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 1

 TERMINÉ 

Functional analysis of SCOC and FEZ proteins in autophagy using mammalian cell models and zebrafish (SCOC and FEZ)

Date du début: 1 avr. 2013, Date de fin: 31 mars 2015,

Autophagy is a conserved, highly regulated degradative pathway transferring cytoplasmic components in autophagosomes to lysosomes providing energy for cellular metabolism. In multicellular organisms autophagy is essential for tissue homeostasis and deficient autophagy is implicated in a broad range of diseases e.g. cancer and neurodegenerative disorders. To develop therapeutic strategies targeting ...
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 1

 TERMINÉ 

A molecular view of chromosome condensation (CHROMOCOND)

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

Eukaryotic cells inherit much of their genomic information in the form of chromosomes during cell division. Centimetre-long DNA molecules are packed into micrometer-sized chromosomes to enable this process. How DNA is organised within mitotic chromosomes is still largely unknown. A key structural protein component of mitotic chromosomes, implicated in their compaction, is the condensin complex. In ...
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 1

 TERMINÉ 

Function of centromeres during meiotic bouquet stage and protein composition of telomeres (meiotic centromeres)

Date du début: 31 juil. 2012, Date de fin: 30 juil. 2014,

Meiosis is a fundamental process in cell biology. During meiosis several unique features events occur such as segregation of homologs rather than sister chromatids and repair of double strand breaks by recombination of the homologs happen. During the first reductional meiotic division, the telomeres cluster in a formation called "bouquet". The bouquet is important for the establishment and maturat ...
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 1

 TERMINÉ 

Identification of important regulators of metastasis in pancreatic cancer (Cancer metastasis)

Date du début: 1 juil. 2012, Date de fin: 30 juin 2014,

Pancreatic cancer is one of the leading causes of cancer-associated mortality. One of the primary contributing factors is late diagnosis of the disease, resulting in established metastatic cancer before symptoms emerge. This form of cancer is characterised by a number of well-defined genetic alterations including oncogenic mutation of K-Ras and inactivating mutation of p53, SMAD4 and CDKN2A. Co ...
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 1

 TERMINÉ 

"DNA damage response and genome stability: The role of ATM, ATR and the Mre11 complex" (AAMDDR)

Date du début: 1 juil. 2008, Date de fin: 30 juin 2013,

"Chromosomal DNA is continuously subjected to exogenous and endogenous damaging insults. In the presence of DNA damage cells activate a multi-faceted checkpoint response that delays cell cycle progression and promotes DNA repair. Failures in this response lead to genomic instability, the main feature of cancer cells. Several cancer-prone human syndromes including the Ataxia teleangiectasia (A-T), ...
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 1

 TERMINÉ 

Imaging influenza nucleic acid recognition by RIG-I in living cells (RIG‐I Live Imaging)

Date du début: 1 mai 2011, Date de fin: 30 avr. 2013,

Despite of intensive research the last decades, viral infection still represents a serious threat to human health. One crucial aspect of the defence against viral infection is the activation of the host innate immune response. Recent advances have highlighted the crucial role of the RIG-I receptor in triggering IFN synthesis upon virus infections. This virus sensing pathway mediated by RIG-I is cr ...
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 1

 TERMINÉ 

The role of Rab7 in axonal retrograde transport and human pathologies (retrograde transport)

Date du début: 1 févr. 2011, Date de fin: 31 janv. 2013,

Neurons are highly polarized cells that depend on anterograde and retrograde transport for survival, differentiation and maintenance of their morphology. Recently, impairment of axonal trafficking has been implicated as a causative agent in a number of human neurodegenerative disorders, such as Charcot-Marie-Tooth type 2B (CMT2B) neuropathy. CMT2B is characterized by the selective loss of motor an ...
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 1

 TERMINÉ 

The role of hypoxia-inducible factors in human haematopoietic stem cell biology and leukaemogenesis (HSCs and HIF)

Date du début: 1 juil. 2010, Date de fin: 8 janv. 2013,

Mammalian haematopoiesis in the adult takes place predominantly in the bone marrow (BM) where a population of haematopoietic stem cells (HSC) are located. HSC are able to self-renew and give rise to all the blood cell types. The fate choice of HSC to either self-renew or differentiate is controlled by an interplay between intrinsic mechanisms and extrinsic signals from the surrounding environment ...
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 1

 TERMINÉ 

Investigation of a dependency of RAS-driven cancers on matrix metalloproteinase-7 (RAS and MMP7)

Date du début: 1 janv. 2011, Date de fin: 31 déc. 2012,

Activating point mutations in RAS are present in a large number of tumours. Besides treating tumours by reversing the effects of oncoproteins through inhibition, another approach is to use therapies that target tumour-specific vulnerabilities caused by the oncogenic state. To investigate this possibility, an siRNA screen has been performed in order to identify new genes necessary for the RAS-drive ...
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 1

 TERMINÉ 

Structural and kinetic basis of evolutionary conserved and divergent microtubule plus end tracking mechanisms (Microtubule plus end)

Date du début: 1 janv. 2011, Date de fin: 31 déc. 2012,

In eukaryotic cells the microtubule (MT) cytoskeleton is of crucial importance for many essential cellular functions. The determination of cell morphology, intracellular transport, chromosome segregation in mitosis, and cell motility belong to the processes carried out by MTs. Aberrant cell morphology, developmental diseases and promotion of malignant transformations in animal cells are results of ...
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 1

 TERMINÉ 

Molecular control of vascular remodelling: A role for Wnt signalling (WNT VASCULAR REMODEL)

Date du début: 1 août 2010, Date de fin: 31 juil. 2012,

"A functional network of blood vessels is essential for all aspects of growth and organ function during embryonic development and adult life. A wide number of human disorders are related to vascular defects like cancer, diabetic retinopathy or stroke. During vascular remodelling, superfluous blood vessels regress in a process named vascular pruning. In contrast to the molecular mechanisms controll ...
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 1

 TERMINÉ 

Investigating the Functional Implications of MICA Polymorphisms (IFIMAP)

Date du début: 1 juil. 2010, Date de fin: 30 juin 2012,

"It is increasingly clear that physico-chemical dysregulation of epithelial cells leads to the upregulation of stress-antigens that make the cells visible to sets of lymphocytes that include gamma delta T cells and NK cells. This form of stress-surveillance can make significant contributions to tumour immunology; transplant rejection; and inflammatory diseases. A central molecular axis underpinnin ...
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 1

 TERMINÉ 

“The role of ALC1, a novel ATP-dependent chromatin remodelling protein, in transcriptional regulation, tumorigenesis and neurodegeneration” (chromALC1hcc)

Date du début: 1 mars 2011, Date de fin: 31 mai 2012,

The genome is continuously exposed to DNA damaging insults that induce a wide variety of lesions. For a proper DNA damage signalling and repair, chromatin remodelling is most likely a prerequisite. Poly(ADP-ribose) (PAR) is known to induce chromatin relaxation at DNA damage sites but how this is achieved remains unclear. My host lab recently identified ALC1 (Amplified in Liver Cancer 1) that binds ...
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 1

 TERMINÉ 

The role of JNK/c-Jun pathway in axonal damage and neuronal regeneration (JNKNeuroreg)

Date du début: 31 mars 2010, Date de fin: 30 mars 2012,

Interruption of axons results in a characteristic reaction of the injured neuron, the so-called axonal response, which aims to induce axon elongation and to achieve a re-construction of effective synapses. Nerve fiber transection elicits a complex neuronal response that leaves neurons poised between death and regeneration. Although the signals underlying this dichotomy are not fully understood, so ...
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 1

 TERMINÉ 

Functional characterization of indirect dendritic cell activation and its impact on adaptive immunity (DC-ACTIVATION)

Date du début: 31 mars 2010, Date de fin: 30 mars 2012,

"During infection, recognition of the infectious microorganism by the innate immune system leads to dendritic cell (DC) activation. This process is essential for the induction of antigen-specific adaptive immune responses. DC can be activated directly by conserved pathogen molecules or indirectly by inflammatory mediators released by other cell types that recognized such molecules. However, recent ...
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 1

 TERMINÉ 

Chromosomal addresses and mechanism of chromatin binding by the Scc2/Scc4 cohesin and condensin loading complex (Chromosome Stability)

Date du début: 1 janv. 2010, Date de fin: 31 déc. 2011,

In eukaryotic cells, cohesion between sister chromatids allows chromosomes to biorient on the metaphase plate and holds them together until they separate into daughter cells at anaphase onset. Accurate control of the mechanisms implicated in sister chromatids cohesion after DNA replication and chromosome condensation during mitosis are essential for faithful chromosome segregation during cell divi ...
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 1

 TERMINÉ 

DNRG-1 as a marker to develop better models for characterising human and mouse dendritic subsets and for analysing their functional role in vivo (CD8DC Functions)

Date du début: 1 oct. 2009, Date de fin: 30 sept. 2011,

The dendritic cell (DC) system of antigen-presenting cells controls immunity and tolerance. The unresolved issues on DC heterogeneity represent an important hurdle in the development of DC-based immunotherapies. The identification of the DNGR-1 marker by the host lab allows us to develop better models for characterising human and mouse DC. In the mouse, this marker is selectively expressed in mous ...
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 1

 TERMINÉ 

Functional Analysis of dASPP/Boa, novel regulators of dCsk in epithelial growth and morphogenesis (dASPP/Boa proteins)

Date du début: 1 oct. 2009, Date de fin: 30 sept. 2011,

Src-family kinases play major roles in promoting adherens junctions remodelling in development and metastasis. Their activities are negatively regulated by C-terminal Src kinase (Csk). The host lab it has recently shown that Drosophila Ankyrin-repeat, SH3-domain and Proline-rich-region containing (dASPP), together with Boa the homology of mammalian Ras association domain family 8, regulates the fu ...
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 1