Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The role of JNK/c-Jun pathway in axonal damage and neuronal regeneration (JNKNEUROREG)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2010-03-31
End date: 2012-03-30
Duration (months): 24.0
Total project cost (EUR): 171867.63
EU funding (EUR): 171867.63
Participants: 1
Project status: CLOSED

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, some are mediated by the induction of immediate-early transcription factors of the AP-1 family, a key regulator in crucial cellular events. AP-1 activity is regulated, in part, by the phosphorylation of its c-Jun component by the Jun N-terminal Kinases (JNKs). Recent work has confirmed the notion that c-Jun functions as the trigger of the axonal response during neuronal regeneration in the CNS and strongly supports the perception of c-Jun action as a “double-edged sword” promoting post-traumatic neuronal cell death as well as axonal regeneration. The goal of this project is to better understand the function of the JNK/c-Jun pathway during neuronal regeneration by generating and employing gain and loss-of-function transgenic mice models and to clarify the role of JNKs/c-Jun phosphorylation in the neuronal response to axonal damage. The assessment of the reinnervation after injury in these transgenic lines will use suitable regeneration paradigms. We are also interested in identifying new JNK/c-Jun mediators that could play a role in the axonal response to injury. Thus, future perspectives towards the strengthening of European potential research could derive from this study. This project integrates well in the FP7 program, and will applicate knowledge and biotechnology for health. The accomplishment of the project would contribute significantly to the acquisition of new relevant data on JNK functions in neuronal death and axonal regeneration, which is indispensable to predict the outcome of JNK/c-Jun system inhibition as a putative therapeutical strategy.

Keywords: health sciences,neurobiology,molecular biology,neuronal cell death,axonal damage,c-jun,jnk.
Developmental Impact of MLL-AF4 Fusion Gene linked to Infant Acute Lymphoblastic Leukaemia on Human Stem Cell Fate (LEUKAEMOGENESIS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2009-09-01
End date: 2011-08-31
Duration (months): 24.0
Total project cost (EUR): 219298.04
EU funding (EUR): 219298.04
Participants: 1
Project status: CLOSED

The MLL gene is located in chromosome 11q23 and is implicated in &gt;40 different chromosomal translocations, generating distinct leukaemic fusion genes. Unlike other MLL fusion proteins, t(4;11) MLL-AF4 is always found in infant pro-B-ALL with a dismal prognosis in infants and adults. In infant ALL where t(4;11) MLL-AF4 is very common (&gt;80%), the gene fusion arises in utero. However, very little is known about the nature of the target cell for transformation in the embryo/foetus and the mechanisms accounting for its B-cell lineage affiliation. Haematopoietic stem (HSC) and progenitor (HPC) cells represent likely targets for transformation. However, mouse models and transformed cell lines have been used with only modest success to model the effects of MLL-AF4 and the disease phenotypes achieved do not faithfully mimic those seen in the actual infant disease. Moreover, MLL-AF4 protein seems toxic when retrovirally over-expressed in mouse or human stem cells. Here, we propose to explore the developmental impact of MLL-AF4 on human haematopoietic stem cell fate through consideration of distinct ontogeny (embryonic and cord blood-CB-) and hierarchical (HSCs and HPCs) stages of development. Based on state-of-the-art lentiviral and TAT-protein transduction technology, MLL-AF4 will be delivered into human cells in distinct ontogenic and hierarchical positions including: hESCs, CB-HSC and CB-HPCs. The potential transformation effects of MLL-AF4 will be assayed in vitro and in vivo by its ability to disrupt the balance between self-renewal and differentiation. These novel studies will provide insights into the developmental impact of MLL-AF4 on human stem cell transformation and fate, improving our understanding of the molecular pathogenesis and aetiology of this leukaemia. Finally, to study this complex genetic infant leukaemia it would be desirable to follow the development of cells carrying the disease mutation in the &quot;dish&quot; and see at which point the cells&apos; function fails

Keywords: health sciences,haematology,oncology,mll-fusion genes,childhood acute linfoblastic leukemia (all),embrionic and adult stem cells,induced pluripotent stem cells (ips)
A study of TGF-beta effects on breast cancer stem cells (TGF-BETA AND BCSCS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2010-01-01
End date: 2011-12-31
Duration (months): 24.0
Total project cost (EUR): 180783.75
EU funding (EUR): 180783.75
Participants: 1
Project status: CLOSED

A highly tumourigenic subpopulation of cancer cells has recently been identified in primary and metastastatic breast cancer. This minority of cells termed tumour-initiating cells or “cancer stem cells“ (CSC) has been shown in several solid tumours to bear stem cell features such as the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumour. Correlating with this, several pathways and genes required for normal stem-cell function are activated in cancer cells and play essential roles in tumourigenesis. However, the specific molecular mechanisms through which CSCs exert their tumourigenic effects remain unknown. The TGF-beta pathway is a key player in mammalian biology, and its misregulation can result in tumour development. Increasing evidences are starting to elucidate the mechanistic basis and clinical relevance of TGF-beta’s role in cancer, yet its complex and pleiotropic nature requires still a much profound understanding of the pathway. The proposed project aims to study a yet unidentified role of TGF-beta in breast cancer stem cell regulation by analyzing human breast cancer cell lines as well as fresh breast tissue samples derived from primary tumours and malignant pleural effusions from patients with breast cancer of diverse grade and stage. TGF-beta regulation of the different subtypes of breast progenitor cells will be assess by colony forming cell and mammosphere-initiating cells assays as well as by an innovative xenotransplantation assay in vitro and in vivo respectively. Moreover, a transcriptomic approach will be designed to discern the mechanisms and molecular determinants of TGF-beta&apos;s role in breast stem cell regulation. By developing this project, we will decipher how TGF-beta regulates breast stem/progenitor cell functions, paving the way for a better understanding of its complexity and therapeutic potential.

Keywords: stem cells,tgf-beta,breast cancer,translational research,genomics
Ethical, Legal, and Social Aspects and Implications of Direct-to-Consumer Genetic Testing (ELSAIDTCGT)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Belgium
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2009-05-22
End date: 2011-05-21
Duration (months): 24.0
Total project cost (EUR): 220226.8
EU funding (EUR): 220226.8
Participants: 1
Project status: CLOSED

With ongoing genetic discoveries and improvements in technology, more genetic tests are made available in a clinical context than ever before. Along with the increase in genetic tests offered there has been a recent rise in companies providing various genetic tests directly-to-consumers (DTC) bypassing the traditional face-to-face meeting with a health care professional. DTC genetic tests have generated various concerns with regard to tests’ analytical and clinical validity, as well as clinical utility; issues related to the quality of pre- and post-test counselling; and the lack of legal regulation. The overall objectives of this research project are to investigate the ethical, legal and social aspects and implications of the provision of genetic tests directly to consumers as is currently done by various companies. Five specific goals form the basis of this work: Firstly, a systematic and indepth review of the field of DTC companies will be performed using content analysis of company web sites. Secondly, this project aims to compare the existing regulatory framework of DTC genetic testing in Europe and North-America (US and Canada). Thirdly, the attitudes of European and North-American geneticists regarding the provision of direct-to-consumer genetic services will be surveyed and analyzed. Fourthly, as a case study of such services, companies offering tests for psychiatric diseases as well as the potential consequences of such services will be investigated. Finally, the last goal will be to disseminate the knowledge developed and to stimulate international and interdisciplinary collaboration by developing a website and organizing an international workshop, network, and conference. Dr. Heidi Howard, (Ph.D. Genetics 2003, MA Bioethics 2008) will, by her background in genetics and ethics, provide a complimentary approach to the multidisciplinary character of the Centre for Biomedical Ethics and Law (K.U.Leuven).

Keywords: ethics in health sciences,biomedical ethics,health law,medical genetics,genomics
Design, synthesis and evaluation of novel ligands of NPY Y1 receptor as potential anti-cancer drug carriers. (CANPY)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-09-01
End date: 2010-08-31
Duration (months): 12.0
Total project cost (EUR): 85492.68
EU funding (EUR): 85492.68
Participants: 1
Project status: CLOSED

Neuropeptide Y (NPY) is a hormone which is the most abundant neuropeptide found in the mammalian central nervous system. It was proved that NPY is implicated in several highly important biological functions such as food intake, vasoconstriction, orexigenic effects, seizures, anxiety, thermogenesis, cardiac hypertrophy, pain modulation and hormone secretion. These activities are mediated by six receptors namely: Y1-Y6. Recently, it was proved that NPY is also involved in breast cancer growth. Experiments have shown that NPY Y1 receptor was expressed mainly in cancer cells, while NPY Y2 receptor was found mostly in healthy cells. Thus, selective ligands of NPY Y1 receptor could be very promising anti-cancer drug carriers, what was already shown in preliminary experiments at the laboratories of the host institutions. There are some known NPY receptors antagonists, both of peptidic (cyclic or linear constrained) and non-peptidic structure. The most promising are constrained linear peptide analogues of C-terminal fragment of NPY with beta-aminocyclopropanecarboxylic acids (beta-ACCs) as foldamers incorporated. However, these compounds exhibit some important disadvantages caused by their chemical reactivity. We propose application of beta-aminocyclopentanecarboxylic acids as peptide structure constraining units in order to obtain NPY Y1 active and selective ligands. Application of these natural amino acids analogues holds the promise to overcome all problems described for beta-ACCs. The synthesis of stereoisomerically pure beta-aminocyclopentanecarboxylic acids analogues of arginine and glutamine, followed by automated synthesis of NPY peptide analogues will give a vast library of potential NPY Y1 ligands. Their activities will be further verified by in vitro experiments and the application as anti-cancer drug carriers will be tested. Moreover, analysis of their conformation in solution will give the possibility to find structure-activity relationships.

Keywords: peptides,beta-aminocyclopentanecarboxylic acids,neuropeptide y,receptor ligand,organic synthesis,solid phase peptide synthesis,conformation,foldamers.
Fungal dimorphism and plant infection during Magnaporthe grisea – rice interaction (MAGNAFACT)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-10-08
End date: 2011-10-07
Duration (months): 24.0
Total project cost (EUR): 181350.76
EU funding (EUR): 181350.76
Participants: 1
Project status: CLOSED

Magnaporthe grisea has emerged as a model system for the elucidation of mechanisms of fungal pathogenesis in crops. During the leaf infection process, the hyphal tip of a germinated conidium swells to form a melanised penetration structure known as an appressorium. Subsequently, M. grisea penetrates the leaf epidermis and develops a pseudohyphal and filamentous-like growth to colonise the first infected cell. We plan to use a multidisciplinary approach which includes transcriptomics, cell biology, biochemistry and bioinformatics to elucidate the genetic components required for pathogenesis-related development in M. grisea. The programme of work will be achieved through the functional characterisation of M581 mutant defective in bulbous growth on PS-PHIL. Although several mutants defective in IH growth have been identified in our laboratory, M581 constitutes one of the most interesting mutants for functional characterisation for several reasons. First, its hyperbranching phenotype which has, in other pathogenic filamentous fungi, been associated with reduced host virulence. Second, M581 is tagged in the putative transcription factor MgRFEG, which, due to the nature of the screen, suggests that MgRFEG is regulated by the MAPK PMK1 pathway. We plan to investigate the role of this new putative transcriptional regulator by adressing the following questions: i) What is the function of MgRFEG during plant colonisation and when is it required by the fungus to colonise plant cells? ii) Which genes are differentially expressed during the dimorphic transition of M. grisea on PS-PHIL surfaces and which are regulated by MgRFEG? iii) What are the target genes of MgRFEG and what is the sequence identified by MgRFEG in the promoter regions of these genes?

Keywords: natural sciences,crop protection
Assessment of wet peroxide oxidation using innovative catalysts for removal of fuel oxygenates from contaminated water (FUEL OXYGENATES WPO)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-03-01
End date: 2011-02-28
Duration (months): 24.0
Total project cost (EUR): 162130.93
EU funding (EUR): 162130.93
Participants: 1
Project status: CLOSED

Fuel oxygenates were developed in the 1970s as octane enhancers. Methyl tertiary butyl ether (MTBE) is by far the most commonly used oxygenate worldwide. Ethyl tertiary butyl ether (ETBE), having similar physical-chemical properties, is becoming a preferred alternative to MTBE in some countries due to tax incentives connected with biomass-derived ethanol which is utilized in ETBE production. As a result of its physical-chemical properties and resistance to biodegradation, MTBE persists in groundwater for long time. Several highly MTBE-polluted sites have been identified in Europe in the last years, particularly in Germany. The currently applied processes for removal of MTBE from groundwater (e.g. stripping and adsorption on activated carbon) require high operation costs. With regard to cost-effective management of contaminated sites and accomplishing the new EU chemical legislation there is clearly a need for the development of innovative, safe and efficient technologies of fuel oxygenates treatment. The main scientific aim of the present project is the assessment of wet peroxide oxidation (WPO) of fuel oxygenates (mainly MTBE and ETBE) using innovative catalysts based on Fe-containing zeolites. The project combines two main objectives: I) improvement of the knowledge about the mechanisms of the catalytic process II) proof-of-principle of the developed process by means of a pilot scale test at a field site In the first period laboratory experiments will be conducted involving (1) synthesis and/or selection of new Fe-containing zeolites, (2) characterization of the catalysts, (3) catalytic activity tests under different conditions including column experiments and (4) studies on the reaction mechanism. In the second period the knowledge acquired in the laboratory experiments will be applied for a pilot scale test under real conditions.

Keywords: mtbe,zeolites,fenton,catalysis,water treatment
Discovering New Determinants of Epithelial Cell Polarity (NEW POLARITY FACTORS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2009-10-01
End date: 2011-09-30
Duration (months): 24.0
Total project cost (EUR): 246983.34
EU funding (EUR): 246983.34
Participants: 1
Project status: CLOSED

Multicellularity requires the organization of cells into specialized tissues. Cells that make up epithelial tissue are polarized; distinct outer (apical) and inner (basal) faces are central to their purpose. Previous studies in animal and cell culture model systems have revealed a number of polarity determinants that act coordinately to establish and maintain epithelial cell polarity under normal conditions. Recent work in Drosophila melanogaster has demonstrated that under starvation conditions, normal polarity signaling is not sufficient; activation of a distinct low-energy polarity pathway is required to maintain polarity. This low-energy polarity pathway is mediated by the LKB1-AMPK signaling module, which acts as a sensor of energy availability. Additional components of the pathway include dystroglycan and the growth regulator TOR, which are not required for epithelial cell polarity except under starvation conditions. Intriguingly, LKB1, AMPK1, dystroglycan, and TOR are all associated with incidence or progression of human epithelial cancers. These findings reveal important, yet unexplored connections between cell polarity, energy-dependent signaling, and cancer. A critical step in the investigation of these links is the identification of additional factors mediating both the low- and normal energy polarity pathways. Large-scale reverse genetic screening in Drosophila provides a powerful, new, and comprehensive approach to this problem. Recent advances in RNAi technology enhance and streamline the screening process, allowing for multiple targeted questions to be addressed. Accordingly, the aims are as follows: Aim 1: Identify novel factors involved in regulating epithelial cell polarity under low-energy conditions. Aim 2: Identify factors required for polarity under normal but not low-energy conditions.

Keywords: epithelial cell polarity,ampk,low-energy,rnai,drosophila
Regulation of plant growth by MADS box organ identity genes (MADS AND GROWTH)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Netherlands
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-06-01
End date: 2012-05-31
Duration (months): 36.0
Total project cost (EUR): 169425.4
EU funding (EUR): 169425.4
Participants: 1
Project status: CLOSED

The development of organs in the plant body occurs post-embryonically and can be characterised by three distinct steps. Firstly, the position of future organ primordia must be specified. Subsequently the identity of organs is determined, followed by differentiation and growth of specialised cell types. Although substantial amount of data generated in the past resulted in identification of players involved in each step, the crucial question how organ identity determination is linked to organ growth and differentiation remains to be addressed. Several preliminary observations imply that genes essential for the specification of floral organ identity, namely MADS box transcription factors, might also play important roles in later steps of organ development and growth. Pilot experiments revealed that MADS box transcription factors are expressed during later steps of organ development and are able to interact with proteins involved in the regulation of organ growth, like TCP transcription factors. The main objective of my research will be to characterise the exact function of MADS box organ identity genes in the molecular and cellular processes underlying growth and establishment of final organ size. I intend to focus predominantly on the development of the floral organs sepals and petals in the model species Arabidopsis given their simple structure yet distinct size and identity. I will confirm and identify “late” interaction partners and targets of the MADS box proteins. Furthermore, the role of the identified genes and proteins in the growth process of floral organs will be analysed by achieving time and site specific activation/inactivation. The proposed research will not only substantially contribute to the knowledge about regulation of plant growth, but will also open new horizons in the field of plant development. Detailed characterisation of molecular mechanisms governing flower and hence fruit growth could provide tools for future agricultural applications.

Keywords: plant development,flower development,mads box,tcp,transcription factors,floral organ identity,growth,arabidopsis,biomass