Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Mechanism of cellular IRESes translation (CELLULAR IRESES)

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: Germany
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2009-08-01
End date: 2011-07-31
Duration (months): 24.0
Total project cost (EUR): 162130.93
EU funding (EUR): 162130.93
Participants: 1
Project status: CLOSED

The central importance of translation control in cancer is just beginning to be fully appreciated. Translation normally initiates with the recruitment of the initiation factors to the 5’ cap of the mRNA for ribosome binding. Curiously, some normally capped cellular messages, which are involved in cell-cycle control, growth and apoptosis, rely alternatively on an internal ribosome entry site (IRES) at their 5’ end and the 3’ poly(A) tail to support translation. The advantage conferred by the IRES is obvious during shutdown of cap-dependent translation: these mRNAs remain bound to the polysomes and maintain steady expression. The deregulation of such mRNAs is directly implicated in tumorigenesis and clearly links translation to cancer. The precise mechanism of translation via cellular IRES and its regulation, the structural/sequence consensus, and its use remain largely unexplored. Here, using the pro-oncogenic c-myc IRES as model, we propose to investigate the role of the 3’poly(A) tail and the possible involvement of distinct set of regulatory factors for the IRES activity, which does not require the canonical poly(A) tail partner, PABP. We will use innovative functional proteomic approaches, which include capturing the RNP complex formed during ribosomal recruitment, and the establishment of high throughput siRNA-based in vivo and in vitro screening assays. Upon completion of the project, we will have a functional understanding of how the poly(A) tail enhances ribosome recruitment in a non-canonical fashion. These results will enable us to gain insight on mechanistic details of translation control. This research will contribute in EU excellence and competitiveness by covering a key area of basic biological process with a strong interest for Europe for its clear relevance to human diseases. It will raise the potential avenue for novel therapeutic strategies against translation and thus hold great promises to turn the research into useful valuable innovation.

Keywords: translation control,cellular ires,poly(a) tail,cancer and translation,functional proteomic approach
Protein engineering for encapsulation and intracellular transport (PROTENGENCTRANS)

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: Switzerland
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-04-01
End date: 2011-03-31
Duration (months): 24.0
Total project cost (EUR): 181368.45
EU funding (EUR): 181368.45
Participants: 1
Project status: CLOSED

The main goal of this project is to develop a system for effective encapsulation and transport of negatively charged guests into living cells using an enginnered protein capsid. The research in prof. Hilvert&apos;s group demonstrated that it is possible to engineer the inner surface of a capsid formed by lumazine synthase from Aquifex aeolicus (AaLS) to accept positively charged guests while retaining the icosahedral structure. In my project I will be addressing the following issues: - Engineering the inner surface of the AaLS to express positively charged aminoacid residues maintaining the ability of the mutant to form an icosahedral capsid - Investigating stability and potential selectivity of guest encapsulation by the modified capsid - Attaching a delivery tag to the outer surface of the capsid in order to make it cell-permeable - Enabling efficient release of the cargo after cellular uptake, by attaching a degradation tag. The proposed project will provide us with a complete system for coating, intracellular transport and release of negatively charged biomolecules. It will be used to internalize membrane-impermeable molecules like siRNA, negatively charged GFP, and in perspective other proteins or oligonucleotide-based molecules. Based on our results, novel systems for regulating gene expression and investigating mechanisms of RNA interference may be developed. The use of a protein as the encapsulating agent will help to overcome shortages of existing systems for gene therapy using viral vectors, like mutagenesis or immune response. It raises hope for future medical applications of our results.

Keywords: molecular biology,molecular design,de novo design,encapsulation,sirna,enzyme engineering
Molecular mechanisms for the evolution of multicellularity in animals (MMEMA)

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: Spain
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-04-01
End date: 2011-03-31
Duration (months): 24.0
Total project cost (EUR): 218164.02
EU funding (EUR): 218164.02
Participants: 1
Project status: CLOSED

The evolution of multicellular animals (metazoans) from a unicellular ancestor is one of the most significant leaps in the history of life. However, little is known about the mechanisms that enabled it. Upon the acquisition of multicellularity, many molecular level innovations should have occurred, especially in the systems responsible for cell adhesion, differentiation, and cell-cell communication. Investigation of a group of protists (unicellular or colonial eukaryotes) that is closely related to metazoans should provide deep insights into molecular mechanisms for this event. Among such protists, however, only unicellular choanoflagellates have been extensively studied so far. This project aims to fill this missing piece by applying comparative genomics and molecular biological approaches to Codonosiga botrytis, a colonial choanoflagellate and two additional protists Sphaeroforma arctica and Capsaspora owczarzaki, which were recently shown to be closely related to metazoans, like choanoflagellates. To this aim, 1) the complete genome sequences of Sphaeroforma and Capsaspora, which will be exclusively available in the host institute, will be analyzed and compared to those of metazoans, in order to identify the candidate genes that were relevant to the evolution of multicellularity. Then 2) the difference in the expression profiles between the colonial and unicellular stages of Sphaeroforma and Codonosiga will be studied to identify genes responsible for forming the colony, which might represent the ‘ancestral form’ of multicellularity in metazoans. Finally, 3) molecular biological methods will be developed and applied to these protists, and functions of the candidate genes identified in 1) and 2) will be analyzed. This should elucidate the functional ‘innovations’ that enabled the evolution of multicellularity. These data will have a major impact to a wide range of research fields, especially to the ‘evo-devo’, microbiology, and molecular evolution communities.

Keywords: molecular evolution,phylogeny,multicellularity,comparative genomics,genome project,metazoa,holozoa,choanoflagellata,sphaeroforma arctica,capsaspora owczarzaki,codonosiga botrytis
VR Surgical Simulation for training: simulator design, optimisation and assessment (VRSURGICALSIMULATION)

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: 2009-09-07
End date: 2010-09-06
Duration (months): 12.0
Total project cost (EUR): 87067.84
EU funding (EUR): 87067.84
Participants: 1
Project status: CLOSED

The better surgeons are trained, the safer surgery procedures will be. Virtual reality (VR) surgical simulators offer new possibilities for surgeon learning, training and assessment, but they are complex to design, requiring contributions from different disciplines, such as engineering, medicine and psychology. Unfortunately, it is difficult to achieve a proper interdisciplinary communication. Most projects in surgical simulation are strongly influenced by the engineering point of view, with weak contributions from the rest. This unbalance and the lack of industry support often lead to a premature end of the project. The fellowship aim at the Imperial Robotics and Imaging Research Group, in the Faculty of Medicine, is to evolve to a professional maturity and to reach a multidisciplinary view to improve the way simulators are applied to minimally invasive surgery (MIS). The training objectives are focused on enhancing my research skills and strengthening my interdisciplinary knowledge by acquiring medical complementary skills. This will allow to apply my previous background on computer science, VR and simulation techniques (see the commercial insightARTHROVR® simulator) to satisfy surgeons’ needs. The main research objectives are: 1. To develop education and training programs for surgeons based on learning theory, using the potential of virtual reality resources. 2. To research which algorithms and simulation techniques need to be improved in order to make surgical simulators a more valid tool; and to design VR surgical simulators adapted to the surgeons’ needs. 3. To perform surgical simulator assessment and to research on the evaluation of surgical competencies. A Personal Review and Development Plan in conjunction with Dr. F. Bello and the Staff Development Unit at the Imperial will be compiled. They will mentor me, supervising the attainment of the fellowship aims for relevant contribution to European excellence and competitiveness.

Keywords: surgical simulation,virtual reality,surgical assessment,surgical education,surgical training,minimal invasive surgery,force feedback,simulation,computer graphics,3 d modelling
IDENTIFYING INHIBITORS OF PROX1 IN COLORECTAL CANCER (PROX1)

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: Finland
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-03-01
End date: 2011-02-28
Duration (months): 24.0
Total project cost (EUR): 184759.18
EU funding (EUR): 184759.18
Participants: 1
Project status: CLOSED

Colorectal cancer (CRC) is one of the leading causes of cancer related mortality in the developed countries. Interestingly, the host laboratory has recently discovered that the homeobox transcription factor PROX1 is overexpressed in the vast majority of human CRCs as well as in mouse models of intestinal cancer with abnormal beta-catenin/TCF signaling. Furthermore, they provided evidence that PROX1 is regulated by the high concentration of beta-catenin and this regulation seems to be tissue specific. As PROX1 expression was found to be specifically associated with the transition from benign to malignant tumor phenotype and in normal colonic and small intestinal epithelium PROX1 expression is restricted only to some enteroendocrine cells, targeting PROX1 seems to be a novel possibility for anti-CRC drugs. The aim of this proposal is to develop an endodermal cell model for the analysis of PROX1 function in the intestine by using induced pluripotent stem cells, furthermore, to identify inhibitors that regulate PROX1 activity or kill PROX1+ cells in CRC and to validate their effect. To achieve the aims, dominant negative constructs will be generated, the direct target genes of PROX1 will be determined by combining expression and ChIP-on-Chip microarray data, high-throughput chemical library screening will be carried out and the effect of candidates will be validated by using different in vitro and in vivo systems.

Keywords: anticancer therapy,genomics,molecular biology,prox1,chemical library screening,microarray,induced pluripotent stem cell,chip-on-chip
The influence of Her2 status on mammary stem/progenitor cells (HER2 MAMMARYSTEMCELL)

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: 2009-10-01
End date: 2011-09-30
Duration (months): 24.0
Total project cost (EUR): 171867.63
EU funding (EUR): 171867.63
Participants: 1
Project status: CLOSED

c-ERBB2/HER2 is a gene that is found overexpressed in ~25% of mammary tumours, and defines the molecular signature of one of the breast cancer subtypes: the HER2-positive tumour subtype. However, the role of the c-ErbB2 tyrosine kinase and the stem cell of origin of HER2-positive breast cancers are poorly understood. Our project aims to study the relationship between c-ErbB2 function and normal and tumour stem cells, as well as on the origin and development of HER2-positive tumours. First, we will study the effects of overexpressing c-ErbB2, or of knocking its expression down, on in vivo mouse mammary epithelial biology. Lentiviral transduction of primary mouse mammary epithelial cells combined with cleared fat pad transplantation and flow cytometric analysis of the resulting outgrowths will be used to study the role of the protein in the normal gland. Second, tumour cells will be isolated from mouse c-ErbB2/neu tumour models and limited dilution transplant assays of cell subpopulations will be used to identify tumour stem cells. Last, a Stop-Flox-Neu mouse model will be combined with transgenic mice carrying the Cre recombinase under different cell-type specific promoters to ask whether activity of c-ErbB2/neu in different subpopulations results in different tumour types with greater or lesser resemblance to human HER2-positive tumours. Identifying the origin of HER2 tumours may be critical for understanding resistance to HER2-targeted therapies as tumours of differing cellular origin may have distinct mechanisms of resistance. The knowledge of the relationships and interactions between HER2 and mammary stem/progenitor cells will be a key aspect of understanding both the role of HER2 in the normal breast and how its over-expression drives breast cancer.

Keywords: breast cancer,her2,erbb2,stem cell,carcinogenesis,mouse mammary epithelium
Functionalised Carbon Nanotube Electrochemical Sensors (FUNSENS)

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: 2009-07-20
End date: 2011-07-19
Duration (months): 24.0
Total project cost (EUR): 171867.63
EU funding (EUR): 171867.63
Participants: 1
Project status: CLOSED

This proposal is for a highly promising young scientist from Spain, Aleix Garcia-Güell, to carry out research and high level training in electrochemical nanoscience, in the renowned Electrochemistry and Interfaces Group at the University of Warwick (UK). The project will greatly enhance the expertise of Garcia-Güell in nanostructured materials, and applications thereof, and take him in significant new directions in the area of single-walled carbon nanotube (SWNT) materials. Specifically, the project will consider novel ideas for a new generation of electrochemical and electrical sensors based on SWNTs and will allow Garcia-Güell to become expert in state-of-the-art nanoscience techniques. The Host Group has recently established that SWNT random networks have very interesting electrochemical properties, including a step change in detection sensitivity, and it is now opportune to build significantly on this work to: (i) develop a detailed understanding of the electrochemistry and conductance of SWNTs at the nanoscale; and (ii) optimise the use of SWNT network and array devices for high sensitivity detection in solution, including bioanalysis. Surface functionalisation will be key part of the programme and Garcia-Güell will bring to bear his expertise, developed in Barcelona and through collaborations in the USA and Germany, on functionalisation strategies using metal nanoparticles and bilayer membranes. The programme is an excellent match of complementary skills of the Fellowship candidate and Host Group and will yield new scientific breakthroughs which will have substantial benefits to European science in this important area. The Fellow will have the opportunity to develop complementary skills essential for career development, through training programmes at the University of Warwick. He will benefit considerably from the extensive network of collaborators of the supervisors and their experience in mentoring young researchers.

Keywords: single-walled carbon nanotubes,electrochemistry,functionalised interfaces,nanosensors,electroanalysis,nanostructured materials
The slide of Punishment. An anthropological study of Post-Modern prison governance (TSPAASPMPG)

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: 2010-02-01
End date: 2012-01-31
Duration (months): 24.0
Total project cost (EUR): 161119.38
EU funding (EUR): 161119.38
Participants: 1
Project status: CLOSED

Developing an interdisciplinary approach between Criminology, Social control theories and Anthropology, the project contributes a new theoretical framework for the analysis of punitive transformation in Europe. It analyses mechanisms and devices of a new model of penal management in the spanish prison system and compares it to relevant data from german and european research projects. The new penal management model has been conceptualized by the researcher as Therapeutic governance. This concept serves to describe the institutional strategies, disciplinary actions and rhetoric orders through which the prison allows to legitimate a new punitive era. Assuming that prison governance is significant for society as a whole the research will analyse control technologies exerted in the prison spaces and how they slide into public dynamics through different agencies. Consecuently another new concept, the Punitive Agora, will be developed. This concept puts under discussion and theorizes three current tendencies of postmodern penality: the download of responsibility for crime control into the community, the emergence of a penal populism rhetoric and the discriminatory criminalization of specific groups. Comparing its findings with studies produced in Germany, Europe and beyond, the project will enable to take up important questions of contemporary governance. Thus, it will allow to consolidate the researcher’s career as an international specialist in the field of Anthropology and Criminology. He will develop and apply new tools for interdisciplinary and comparative analysis and increase his competitiveness in academia. The researcher’s capacity to stimulate collaborations between international departments and research groups will be reinforced. Finally, the project will allow to enhance collaborations between european research partners and to produce high-level european scientific synergies.

Keywords: social anthropology,criminology,therapeutic governance,post modern prison phenomena,punitive agora,interdisciplinary and comparative approach,spain,germany
Discrimination Norms Enforced and Disrupted by Social Networks: A Research Program Using Simulation and Experiments (0DISCRIMINATION)

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: Italy
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2010-01-01
End date: 2011-08-31
Duration (months): 20.0
Total project cost (EUR): 196516.13
EU funding (EUR): 196516.13
Participants: 1
Project status: CLOSED

Recognizable traits (gender, ethnicity, hair color) often provide a basis for negative discrimination, even if there is no statistical basis for differentiation. Still, people act differently towards persons with different traits, as if they had different qualities, for instance with regard to work efficiency. This leads to severe conflicts if discrimination provokes prejudice and stigmatizing that in practice mostly target asymmetrically members of one, disadvantaged category. The proposed research program enriches existing theories about the emergence and maintenance of discrimination by a new perspective: it aims to model mechanisms based on social network relations and incorporates them into the explanations. It tries to find answers under which structural configurations discrimination practices are likely to occur and under which network conditions they can be best avoided. For answering these questions, innovative methodologies will be used: agent-based simulation and experiments. These techniques have only been used to a limited extent targeting the problem of discrimination, but offer a huge potential to extend our limited insight into social mechanisms that maintain discrimination practices. With the help of these methods, the proposed research tries to delineate conditions under which an endogenous breakdown of negative discrimination is promoted by social networks. Particular attention will be devoted to cases of fierce intergroup opposition, in which network segregation is aligned with negative discrimination. Results are expected to help forming efficient policies for fighting discrimination and segregation. The practical objectives of the application are to further develop the skills of the applicant in applying these methods with a help of leading experts, and to embed the research program in a multi-disciplinary environment, where important contributions can be expected from sociologists, economists, computer scientists, and historians.

Keywords: sociology,political sciences,economics,social psychology,modelling networks,discrimination,tolerance,social networks,agent-based simulation,experiments