Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Neoadjuvant Nanomedicines for vascular Normalization (NEONANO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Germany
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1356000.0
EU funding (EUR): 1356000.0
Participants: 1
Project status: CLOSED

The aim of my proposal is to establish ‘Neoadjuvant Nanomedicines for vascular Normalization’ (NeoNaNo) as a novel concept for improving the efficacy of combined modality anticancer therapy. This concept is radically different from all other drug targeting approaches evaluated to date, since nanomedicines are not used to directly improve drug delivery to tumors, but to normalize the tumor vasculature, and to thereby indirectly improve drug (and oxygen) delivery. The need for such an alternative concept can be exemplified by taking the (pre-) clinical performance of nanomedicines into account: whereas in animal models, they generally improve both the efficacy and the tolerability of chemotherapeutic drugs, in patients, they often only attenuate the toxicity of the intervention, and they fail to improve the efficacy of the drug. To overcome this shortcoming, I here propose to use corticosteroid-containing nanomedicines, targeted to tumor-associated macrophages (TAM), to inhibit pro-inflammatory and pro-angiogenic signaling by TAM, and to thereby homogenize the tumor vasculature, increase tumor perfusion and reduce the interstitial fluid pressure. As a result of this, the tumor accumulation, intratumoral distribution and antitumor efficacy of subsequently administered chemotherapeutics, as well as of radiotherapy (because of enhanced oxygen delivery) can be substantially improved. To achieve these goals, liposomal, polymeric and micellar corticosteroids, several different animal models, and several different imaging agents and techniques will be used to (I) visualize and optimize nanomedicine-mediated vascular normalization; to (II) potentiate chemotherapy; and to (III) potentiate radiotherapy. These efforts will not only provide a solid basis for a completely new paradigm in nanomedicine research, but they will also result in novel, broadly applicable and clinically highly relevant combination regimens for improving the treatment of advanced solid malignancies.

Keywords: nanomedicine drug targeting combination therapy
Spatiotemporal regulation of epidermal stem cells by circadian rhythms: impact on homeostasis and aging (STEMCLOCK)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Spain
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1495484.0
EU funding (EUR): 1495484.0
Participants: 2
Project status: CLOSED

Most adult stem cells are compartmentalized in functionally deterministic niches where they self-renew and maintain homeostasis. From there, stem cells are instructed by combinations of signals and spatial tensile forces which they translate into a specific behavior. However how stem cells spatiotemporally coordinate their stem cell potential with niche- and systemic cues is poorly understood. These issues are essential since perturbations in stem cell function can cause tissue malfunction, such as tumorigenesis and aging. We propose to perform a systematic analysis to identify the molecular causes that underlie epidermal stem cell aging. We will focus on the interplay between circadian rhythms and stem cell function. The circadian machinery anticipates and synchronizes the daily function of tissues according to the entrainment by natural changes in light and metabolism. We have shown that the molecular clock fine-tunes the behavior of epidermal stem cells by imposing oscillations in the expression of stem cell regulatory genes. These oscillations provide stem cells with a spatiotemporal axis for responding to dormancy, activating, and differentiation cues. Notably, the stem cell clock is naturally dampened upon aging, and forced circadian arrhythmia causes severe epidermal aging and predisposition to tumorigenesis. We now propose to understand how the circadian clock coordinates the communication between stem cells with local and systemic cues, and how these are perturbed during aging. Specifically we aim: i) To study whether circadian rhythms coordinate the function of niche cells and epidermal stem cells; ii) To identify the molecular causes underlying the age-related dampening of the stem cell clock. We will combine large-scale genomic data, mouse models of circadian arrhythmia, and bioinformatic analysis. We hope to unveil some of the molecular causes underlying the loss of communication between epidermal stem cells and their environment resulting in aging.

Keywords: adult stem cells,homeostasis,aging,circadian rhythms,stem cell communication,epidermis
Unveiling the Molecular Basis of RNA Interference with Single Molecule Fluorescence (RNAI)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Netherlands
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-09-01
End date: 2017-08-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Recent groundbreaking discoveries have changed our view on RNA from that of a passive information carrier to an important regulatory element. MicroRNA is a small regulatory RNA that controls nearly all mRNAs in eukaryotic cells. Since this regulation process (termed RNA interference/RNAi) occurs in a sequence-specific manner, we can manipulate gene expression using custom-designed small RNAs. This remarkable discovery introduced the possibility of RNA-based gene therapy and triggered intensive research on the RNA-induced silencing complex (RISC), the core machinery of RNAi. The molecular mechanism of RISC is, however, poorly understood due to the limited spatial and temporal resolution of traditional tools, which has deterred development of an RNAi assay applicable to medical sciences. I will use single-molecule fluorescence to investigate the entire process of RISC action with high spatio-temporal resolution. From ‘RISC assembly’ through ‘target mRNA search’ to ‘target mRNA degradation,’ it requires the cooperative action of multiple RISC components. As the protein-protein and protein-RNA interactions are dynamic processes, it is challenging to study them in bulk where the interactions are diffusion-limited and subsequent processes are masked from observation. With single-molecule microscopy, I will observe all the processes in real time and quantitatively examine the kinetics. In addition, I will dissect the complex processes of RISC action by observing multiple RISC components simultaneously, using multicolor FRET that I have developed. Furthermore, to elucidate the complex nature of RNAi, I will reconstitute protein complexes with a single-molecule immunoprecipitation technique that I have recently innovated. This first single-molecule study on RISC will enable us to reveal novel molecular mechanisms of RNAi. The fruitful outcome will aid the development of RNAi free from off-target interactions, which will lead to RNAi-based gene therapy in the near future.

Keywords: single-molecule spectroscopy,fret,rna interference,microrna,mirna,fluorescence,risc,ago,trbp,dicer,gw182,hsp90,multi-color fret,single-molecule immunoprecipitation,molecular mechanism
Taking Nanotechnological Remediation Processes from Lab Scale to End User Applications for the Restoration of a Clean Environment (NANOREM)

Framework: FP7 — Cooperation
Programme: Nanosciences, Nanotechnologies, Materials and new Production Technologies - NMP
Destination: Nanosciences and Nanotechnologies
Action type: Collaborative project
Countries involved: Germany,Germany,Germany,Israel,Austria,United Kingdom,Spain,Germany,Norway,Czechia,Czechia,France,Italy,Denmark,Netherlands,United Kingdom,Germany,Germany,Switzerland,Spain,Czechia,Portugal,United Kingdom,Czechia,Germany,Germany
Call:  (FP7-NMP-2012-LARGE-6, 2012)
Start date: 2013-02-01
End date: 2017-01-31
Duration (months): 48.0
Total project cost (EUR): 14001041.22
EU funding (EUR): 10393632.0
Participants: 30
Project status: CLOSED

NANOREM is designed to unlock the potential of nanoremediation and so support both the appropriate use of nanotechnology in restoring land and aquifer resources and the development of the knowledge-based economy at a world leading level for the benefit of a wide range of users in the EU environmental sector. NANOREM uniquely takes a holistic approach to examining how the potential for nanoremediation can be developed and applied in practice, to enhance a stronger development of nanoremediation markets and applications in the EU. NANOREM’s ambitious objectives are: 1) Identification of the most appropriate nanoremediation technological approaches to achieve a step change in practical remediation performance. Development of lower cost production techniques and production at commercially relevant scales, also for large scale applications. 2) Determination of the mobility and migration potential of nanoparticles in the subsurface, and their potential to cause harm, focusing on the NP types most likely to be adopted into practical use in the EU. 3) Development of a comprehensive tool box for field scale observation of nanoremediation performance and determination of the fate of NPs in the subsurface, including analytical methods, field measurement devices, decision support and numerical tools. 4) Dissemination and dialogue with key stakeholder interests to ensure that research, development and demonstration meets end-user and regulatory requirements and information and knowledge is shared widely across the EU. 5) Provide applications at representative scales including field sites to validate cost, performance, and fate and transport findings. The NANOREM consortium is multidisciplinary, cross-sectoral and transnational. It includes 28 partners from 12 countries organized in 11 work packages. The consortium includes 18 of the leading nanoremediation research groups in the EU, 10 industry and service providers (8 SMEs) and one organisation with policy and regulatory interest.

Keywords: analytical method dissemination economy ecotoxicology efficiency field application in-situ remediation lab scale market barriers mobility nanoparticles numerical tool nzvi oxidizing reactive reductive
ImpactTracer: Building a Web-Application to Measure and Visualise the Impact of Texts over Time (IMPACTTRACER)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Proof of concept grants
Action type: Support for frontier research (ERC)
Countries involved: United Kingdom
Call:  (ERC-2011-PoC, 2011)
Start date: 2012-05-01
End date: 2013-07-31
Duration (months): 15.0
Total project cost (EUR): 154573.6
EU funding (EUR): 139366.46
Participants: 1
Project status: CLOSED

We are proposing to develop a web-application provisionally called ImpactTracer that allows different types of users to trace the impact of texts on a large number of subsequent texts over time and according to their needs. The collection of texts to be analysed can be assembled by uploading relevant documents or by retrieving them as a result of an internet search. For the process of uploading documents, the application will provide clear instructions as to the accepted formats and data cleansing workflow to follow and how best to achieve this preliminary step. Once the texts are uploaded, the user will then be able to choose what kind of impact s/he wants to measure, which algorithm(s) should be applied accordingly, and how the results should be presented. Presentation of findings could take different forms: firstly, we seek to provide users with quantitative measurements of impact, merging the results of different algorithms and ranking findings according to the accuracy and strength of the underlying method. These can then be viewed online as browsable overviews and summaries or they can be downloaded as a set of reports. Secondly, the goal is to allow for a graphical visualisation of the results, which is particularly important when dealing with a larger collection of documents as quantitative or textual output alone do not allow for an intuitive interpretation of results. The development of impact over time of a group of texts can, for example, be displayed in an interactive timeline with which the user would be able to pan back and forth in time in a visual display of the results.

Keywords: 202022
Materials for a Magnetic Memory in Three Dimensions (M3D)

Framework: FP7 — Cooperation
Programme: Nanosciences, Nanotechnologies, Materials and new Production Technologies - NMP
Destination: Materials
Action type: Collaborative project
Countries involved: France,United Kingdom,Germany,Germany,France,France,Germany
Call:  (FP7-NMP-2012-SMALL-6, 2012)
Start date: 2012-12-01
End date: 2016-11-30
Duration (months): 48.0
Total project cost (EUR): 4051250.67
EU funding (EUR): 2606083.0
Participants: 7
Project status: CLOSED

This project concerns data storage in three dimensions (3D). Conventional planar (2D) devices are expected to reach the limits of scaling within less than a decade. We will develop the materials needed for 3D memories based on magnetic shift-register devices, namely dense arrays of vertical magnetic wires in a matrix (race-track memory, IBM patent). In this concept series of bits are shifted along each wire, requiring only one read/write element per wire. Synthesis will rely largely on bottom-up routes (self-organized anodization, atomic-layer deposition, electroplating) to minimize costs. In order to minimize risks, three different strategies will be explored for coding bits: domain walls in continuous wires; solitons with transverse magnetization in a series of magnetic disks; a hybrid route with discontinuous wires with longitudinal magnetization. Two route will be explored for data shifting: magnetic field, or current (spin transfer torque). Addressing each wire will be demonstrated, using writing methods such as thermally-assisted writing, and reading methods such as a TMR junction embedded in the wire. We address call targets density (5-50Tbit/in2), and reasonable cost per Tbit (2-20€), going beyond the scalability of all-planar devices while remaining very competitive in terms of speed and energy consumption (1-10GHz with zero seek time; 10-100 pJ/bit). In all four targets, 3D magnetic memories promise to outperform Hard Disk Drives, providing more storage capacity with less energy consumption. The project brings together the relevant leading academic research groups in Europe. It aims to set Europe ahead of Asia and the USA in 3D storage, a largely unexplored area with a high potential for innovation. Two SMEs are partners, one for material development (SmartMembranes, world leader in self-organized anodized products), and the European leader in Magnetic-RAM development, Crocus Technology.

Keywords: magnetism,data storage,memory,domain wall,three-dimensional,non-volatile
Identification of Host Determinants for Virus Entry using a Haploid Genetic Approach (VIRAL HOST FACTORS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Netherlands
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1495200.0
EU funding (EUR): 1495200.0
Participants: 1
Project status: CLOSED

The most powerful and direct way to get insight into complex biological systems is to remove individual components and observe the consequences. Cultured human cells are widely used to model and study aspects of human disease. Although human cells can be analyzed and manipulated in numerous ways, their genome has remained refractory to efficient mutagenesis-based analysis. We have developed an insertional mutagenesis-based approach in haploid and near-haploid human cells. We have shown that this approach enables the generation of null alleles for most human genes and can be used to pinpoint genes that are involved in phenotypes of interest. We have made use of parallel sequencing approaches to generate high-density genetic overviews of genes that are required for phenotypic cell states. In a variety of genetic screens we have identified host factors required for infection of cells by influenza virus, the first entry receptor for a Clostridium Difficile toxin and a set of host factors that play a role in the entry of Ebola virus. Importantly, we can carry out and analyze a genetic screen in a period of weeks in a cost-effective manner. This application outlines experiments aimed at identification and detailed characterization of host factors that play a role in Filovirus infection. Moreover, we propose a number of experiments to gain mechanistic insight in the role of the Niemann-Pick C1 cholesterol transporter in entry, tropism and the fusion process of Ebola virus. Furthermore we propose to develop refinements in our screening approach. Finally, we will apply our haploid screening platform to generate a “Host Factors Atlas’ for 50 diverse viruses that infect the human population. We foresee that the outlined experiments will provide an detailed and accurate overview of the unusual entry-route used by Filoviridae, will make our screening platform more powerful and will generate a much-needed overview of host factors used by a compendium of viruses.

Keywords: virus host factors,genetics
The Role of Elimination of Senescent Cells in Cancer Development (ELIMINATESENESCENT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Israel
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-11-01
End date: 2017-10-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Cellular senescence, which is a terminal cell cycle arrest, is a potent tumor suppressor mechanism that limits cancer initiation and progression; it also limits tissue damage response. While senescence is protective in the cell autonomous manner, senescent cells secrete a variety of factors that lead to inflammation, tissue destruction and promote tumorigenesis and metastasis in the sites of their presence. Here we propose a unique approach – to eliminate senescent cells from tissues in order to prevent the deleterious cell non-autonomous effects of these cells. We will use our understanding in immune surveillance of senescent cells, and in cell-intrinsic molecular pathways regulating cell viability, to identify the molecular “Achilles’ heal” of senescent cells. We will identify the mechanisms of interaction of senescent cells with NK cells and other immune cells, and harness these mechanisms for elimination of senescent cells. The impact of components of the main pathways regulating cell viability, apoptosis and autophagy, will then be evaluated for their specific contribution to the viability of senescent cells. The molecular players identified by all these approaches will be readily implemented for the elimination of senescent cells in vivo. We will consequently be able to evaluate the impact of the elimination of senescent cells on tumor progression, in mouse models, where these cells are present during initial stages of tumorigenesis. Additionally, we will develop a novel mouse model that will allow identification of senescent cells in vivo in real time. This model is particularly challenging and valuable due to absence of single molecular marker for senescent cells. The ability to eliminate senescent cells will lead to the understanding of the role of presence of senescent cells in tissues and the mechanisms regulating their viability. This might suggest novel ways of cancer prevention and treatment.

Keywords: cellular senescence
The analysis of mitochondrial dynamics in ageing and neurodegeneration (DYNAMITO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: United Kingdom
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2018-12-31
Duration (months): 72.0
Total project cost (EUR): 1486761.0
EU funding (EUR): 1486761.0
Participants: 3
Project status: CLOSED

The survival of our most active tissues, such as the brain and heart, throughout decades of a human lifespan presents an extraordinary biological challenge. Mitochondria are central to the life and death of these tissues. They provide the cellular energy required by these cells and protect them by buffering potentially lethal levels of cytoplasmic calcium, while at the same time mitochondria produce much of the molecules that cause cellular damage and contain a lethal arsenal of apoptotic cell death machinery. These organelles require exquisite maintenance processes to keep them intact and prevent potentially catastrophic disruption. Failure in mitochondrial homeostasis is strongly linked to age-related conditions such as neurodegeneration. This subject has garnered intense interest recently with emergence that two genes linked to Parkinson's disease, PINK1 and parkin, regulate the autophagic degradation of mitochondria (mitophagy). Mitophagy is coordinated with mitochondrial dynamics, processes vital to neuronal health. While recent work has uncovered the basic mechanisms of PINK1/parkin-induced mitophagy, many questions and caveats surround the current knowledge. Most notably, all studies to date have used in vitro approaches and non-physiological manipulations. Thus, we still have a poor understanding of this process in a physiological context. I will principally use the powerful genetic techniques of Drosophila to investigate the influence of mitochondrial dynamics on maintaining normal neuronal function and survival, and its impact on neurodegeneration, in the context of an intact animal system. I will also use molecular, cell biology and biochemical approaches in mammalian cells to complement our in vivo findings and verify their relevance to human biology. These insights will deliver a greater understanding of the role of mitochondrial dynamics in the health and dysfunction of the nervous system in a physiological context and guide therapeutic developments.

Keywords: mitochondria,mitophagy,parkinson's disease,parkin,pink1,mitofusin,organelle tethering,calcium