Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MAGNIFISCENT (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Technion – Israel Institute of Technology — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1946250.0 €

Imaging defined cells, over extended time, depends on signal strength, stability, accessibility and specificity. Whereas light-microscopy (LM) can provide these, it does not allow imaging of entire intact tissues; imaging-depths and area-size are restricted, and not easily obtained through skin and bone. Magnetic Resonance Imaging (MRI) outperforms LM in these instances; providing images of large-fields-of-view (i.e., mesoscale), at any depth, easily across bone. Nevertheless, MRI suffers from low signals, spatial resolution and cannot detect specific biological targets. To remedy these shortcomings, and significantly extend the capabilities of MRI, we propose a novel chemo-genetic approach—MAGNIFISCENT (MAGNetic Including Fluorescence Imaging of Select Cells with ENzymatic Tags)—to jointly image multiple defined cellular-targets by MRI and LM. In parallel thrusts, we will synthesize a novel family of multifunctional, membrane-permeable, liganded-Contrast-Agents (CA; patented) that irreversibly bind original genetically-encoded enzymatic tags (eTags). When several eTags are expressed in various cells, each will bind its corresponding liganded-CA bearing a unique MRI-signature (‘color’); affording multicolor-MRI of the brain. To mitigate hurdles of expression, we introduce enrichment, an elegant scheme to increase binding-surface for MFS-agents. We estimate it to increase resolution of MRI to the single-cell level. Lastly, developing split-eTags will enable imaging cellular interactions of up to four different cellular populations jointly, a feat never shown before for MRI. We develop an innovative targeted-recombination scheme to ENTRAP neurons destined for apoptosis; a hallmark of neurodegeneration. Together, when combined, select targets will be irreversibly ‘tagged’ for long-term multimodal imaging at high resolutions. The multidisciplinary nature of my group ensures our success in developing this versatile technology for studying the brain in health and disease.

Mots-clés : chemo genetic,contrast agents,genetically encoded reporters,targeted recombination
Projet ERC : BioPoweredCL (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1449750.0 €

Imaging is one of the most powerful technique to visualize molecules, tissues, to understand and follow processes and it is the most used diagnostic tool in vitro and in vivo, Current biomedical imaging techniques can have high sensitivity, good spatial/temporal resolution and, in some cases, high tissue penetration but cannot combine all of these desired properties without using harmful radiations (or toxic labels) or very expensive equipment. Optical imaging techniques represent the best compromise among them; however, their ability to scale to human body is precluded. The main restriction of fluorescence imaging is that it requires light excitation which is limited by tissue absorption and scattering. Such limitations are not present in chemiluminescence imaging since light production occurs through a chemical reaction, resulting in higher penetration depth and best sensitivity. However both natural and artificial chemiluminescent systems require a continuous flow of exogenous reactants since all substrates are irreversibly consumed. BioPoweredCL aims to develop an unprecedented strategy to enable molecular imaging by realizing near infrared luminophores that harvest energy from the cellular respiration chain, in order to emit light without being consumed themselves. BioPoweredCL takes advantage of the most recent progress in artificial light production to develop a novel imaging technique where the absence of an excitation source overcomes the current limitations of fluorescence imaging while the regeneration of the luminophore overcomes the limitations of bioluminescence imaging. If successful it could replace current techniques based on harmful ionizing radiations such as X-rays or γ-rays. To reach such a grand-challenge the work plan is articulated into three different phases: 1) synthesis of new luminophores; 2) electrochemical characterization and energy cell harvesting; 3) in vitro experiments where the full potential of the approach will be validated.

Mots-clés : chemiluminescence,bioluminescence,electrochemiluminescence,luminescence,thermally activated delayed fluorescence,bioimaging,self assembly,luminescent compounds,sensing
Projet ERC : SpreadMRI (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Tübingen — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 502000.0 €

Imaging speed is a key factor to capture rapid changes at high spatial and temporal resolution. A major limitation of magnetic resonance (MR) imaging is its rather low speed compared to other modalities like ultra sound or computerized tomography. We aim to explore two novel concepts to boost MR imaging speed by another order of magnitude compared to existing techniques. SpreadMRI fundamentally steps beyond current concepts of image encoding by exploiting a spectral spin modulation that so far has not been utilized. SpreadMRI is based on the rapid and local modulation of magnetic fields produced by current loops and/or radiofrequency (RF) loops. Applied spectral modulations are in the MHz range bridging the low-frequency band of switched gradients (kHz) and the 100 MHz range of the Larmor frequency. SpreadMRI spreads the bandwidth of gradient-encoded spin frequencies using distinct carrier frequencies originating from a certain region of the object. This spatially unique information will then be used to disentangle parts of the object, and thus to drastically boost imaging speed. Approaching this intermediate frequency band requires to address several basic research questions related to image reconstruction, electromagnetic coupling, spin Physics and possible biological effects. Based on theoretical analysis and exhaustive electromagnetic simulations of dedicated current loop and RF coil arrangements, including variants of different modulation patterns, several types of SpreadMRI coils for human head imaging at 9.4T will be developed and applied for high temporal and spatial functional brain imaging. The specific approach of SpreadMRI will lead to major changes in the hard- and software environment of current MR-scanners. It will not only provide new insight within the areas covered by the proposal, but will definitely benefit conventional MR diagnostic by enabling new applications with a simultaneous reduction of motion artifacts and increased patient throughput.

Mots-clés : magnetic resonance imaging,parallel imaging,medical imaging,ultra high field 9 4 tesla,radiofrequency coils
Projet ERC : PATHOCODE (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Geneva — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIGE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999954.0 €

Immune responses against viruses in the central nervous system (CNS) can result in devastating outcomes. Even non-cytolytic CD8+ T cell interactions, which purge viruses from neurons without triggering cell death, can induce permanent damage. Yet, how this immune response irreversibly disrupts neuronal homeostasis remains unclear. Here, we will elucidate the molecular mechanisms that underlie non-cytolytic CD8+ T cell engagement with infected neurons and their consequences on neuron function in vivo. We hypothesize that inflammatory signalling in neurons, induced by non-cytolytic CD8+ T cell interactions, triggers metabolic and epigenetic changes that underpin permanent neuronal dysfunction. "PATHOCODE" will test this hypothesis by harnessing a unique animal model of T cell-driven virus encephalitis in the following objectives: 1. Discern neuronal subset-specific vulnerabilities and antigen-dependent versus bystander effects in the inflamed CNS. We will perform single nucleus RNA sequencing to examine whether T cell engagement (a) differentially affects molecularly distinct neurons, and (b) affects non-targeted, uninfected neurons. 2. Uncover the consequences of non-cytolytic T cell engagement on neuronal metabolism. We will use cell-specific mitochondrial reporter mice to investigate immune-driven metabolic adaptation of neurons in vivo. 3. Determine how non-cytolytic T cell engagement affects the neuronal epigenome. We will employ cell-specific nucleus/ribosome reporter mice to elucidate how T cell engagement affects the translatome and epigenome of infected cells. 4. Rescue T cell-mediated neuronal dysfunction by restoring metabolic pathways. We will exploit recent CRISPR/Cas9 technological advances to restore neuronal gene expression and uncover the relevance of immune-driven metabolic and epigenomic changes to disease. Our study will thus provide novel molecular concepts about immune-driven neuronal alterations in CNS inflammatory diseases.

Mots-clés : immunopathology,central nervous system,cytotoxic t cells,neurons
Projet ERC : ARTimmune (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Radboud University Nijmegen Medical Centre — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUNMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Immunotherapy has entered centre stage as a novel treatment modality for cancer. Notwithstanding this major step forward, toxicity and immunosuppression remain major obstacles, and illustrate the pressing need for more powerful and specific immunotherapies against cancer. To overcome these roadblocks, in ARTimmune, I propose to follow a radically different approach by developing local rather than systemic immunotherapies. Taking advantage of the architecture of a lymph node (LN), I aim to design fully synthetic immune niches to locally instruct immune cell function. I hypothesize that programmable synthetic immune niches, when injected next to a tumour, will act as local powerhouses to generate bursts of cytotoxic T cells for tumour destruction, without toxic side effects. Single cell transcriptomics on LN, obtained from patients that are vaccinated against cancer, will provide unique insight in communication within immune cell clusters and provide a blueprint for the intelligent design of synthetic immune niches. Chemical tools will be used to build branched polymeric structures decorated with immunomodulating molecules to mimic LN architecture. These will be injected, mixed with sponge-like scaffolds to provide porosity needed for immune cell infiltration. Programming of immune cell function will be accomplished by in vivo targeting- and proteolytic activation- of immunomodulators for fine-tuning, and to extend the life span of these local powerhouses. The innovative character of ARTimmune comes from: 1) novel fundamental immunological insight in complex communication within LN cell clusters, 2) a revolutionary new approach in immunotherapy, by the development of 3) injectable- and 4) programmable- synthetic immune niches by state-of-the-art chemical technology. When successful, it will revolutionize cancer immunotherapy, moving from maximal tolerable dose systemic treatment with significant toxicity to local low dose treatment in the direct vicinity of a tumour

Mots-clés : cancer immunotherapy,chemical engineering,artificial immune sytem,single cell,transcriptomics,3d polymer scaffolds
Projet ERC : SUMMIT (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Johannes Gutenberg University Mainz — Pays : Allemagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2482500.0 €

Immunotherapy is expected to fundamentally change the treatment of cancer patients. Personalized vaccines eliciting immune responses against individual cancer mutations have moved into the spotlight. We have pioneered the field and moved ´cancer mutanome vaccines´ from a mere vision into a disruptive medical concept compatible with current standards of drug development and health care practice. Solving key scientific and technological challenges and building on extensive preclinical studies, we showed in a first-in-human trial potent tumor-directed immunity in every single vaccinated patient, and clinical activity of a novel mRNA-based mutanome vaccine. Given that mutations are a hallmark of cancer, mRNA mutanome vaccines are universal drugs the efficacy of which are unaffected by the cancer type. The aim of this proposal is to ignite the next wave of advancement by addressing four key constraints challenging a full clinical realization of such vaccines. We will address the scarcity of point mutations in many tumors by extending neoepitope discovery to the full spectrum of genetic aberrations. Cancers are heterogeneous and outgrowth of clones unaccounted for by the vaccine is an efficient escape mechanism. We will develop neoepitope prediction algorithms deciphering clonal heterogeneity to inform rational vaccine design and countermeasures against selection of target escape variants. Tumor cell resistance to vaccine-induced T cells due to antigen presentation defects will be addressed by developing strategies for mobilizing the full repertoire of immune effector mechanisms, including antibodies and NK cells. T-cell exhaustion will be tackled by vaccination protocols promoting long-lived memory responses and by combination treatments counteracting tumor-mediated immunosuppression. Finally, we will drive the seamless clinical translation of the scientific findings by close interdisciplinary collaboration with strong and established clinical and industrial partners.

Mots-clés : precision medicine,personalized cancer vaccines,neoepitope prediction,cancer mutanome,immune escape,tumor heterogeneity
Projet ERC : IMPACT HAU (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Bologna — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIBO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999999.0 €

Impact investing is a major emerging phenomenon in global finance that promises to reconcile capitalism with sustainability. It is increasingly embraced by governments, civil society and the private sector in the Global North and South to solve social and environmental problems. The combined crises of climate change, inequality and mass migration in a context of economic austerity have spurred cross-sectoral impact investing partnerships in areas such as green infrastructure, women’s entrepreneurship, agroecology, refugee support and disease prevention. This burgeoning $200bn market promises flexible, holistic and profitable paths to sustainability, attracting major philanthropic organisations and institutional investors boasting fresh ethical and responsible mandates. Is impact investing merely a new frontier for capitalism, or does it represent a revolutionary chapter in global history? Will it benefit communities better than conventional development programmes? The time to answer these questions is now, as impact investing is still in its infancy and the first green and social stock exchanges are opening around the world. IMPACT HAU is an innovative, critical and comparative anthropological study of the moral and political dimensions of impact investing. Inspired by Marcel Mauss’s classic use of the Maori concept of hau, the ‘spirit of the gift’, it focuses on the designers, traders and beneficiaries of impact bonds to produce an empirically driven analysis of the multiple moral orders within contemporary capitalism. Six ethnographic case studies will provide grounded, detailed accounts of the design and implementation of impact investing in Africa, Asia, Europe and the Americas. These will support a critical appraisal of the current consensus among global policymakers and business leaders giving markets a determining role in the ecological transition, testing the theories of sustainability that underpin hopes for a socially inclusive green economy.

Mots-clés : political ecology,anthropology of finance,anthropology of globalization and development,sustainability,environmental anthropology,anthropology of migration,medical anthropology
Projet ERC : DIFFINCL (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Leipzig University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1860875.0 €

Important problems in science often involve structures on several distinct length scales. Two typical examples are fine phase mixtures in solid-solid phase transitions and the complex mixing patterns in turbulent or multiphase flows. The microstructures in such situations influence in a crucial way the macroscopic behavior of the system, and understanding the formation, interaction and overall effect of these structures is a great scientific challenge. Although there is a large variety of models and descriptions for such phenomena, a recurring issue in the mathematical analysis is that one has to deal with very complex and highly non-smooth structures in solutions of the associated partial differential equations. A common ground is provided by the analysis of differential inclusions, a theory whose development was strongly influenced by the influx of ideas from the work of Gromov on partial differential relations, building on celebrated constructions of Nash for isometric immersions, and the work of Tartar in the study of oscillation phenomena in nonlinear partial differential equations. A recent success of this approach is provided by my work on the h-principle in fluid mechanics and Onsager's conjecture. Against this background my aim in this project is to go significantly beyond the state of the art, both in terms of the methods and in terms of applications of differential inclusions. One part of the project is to continue my work on fluid mechanics with the ultimate goal to address important challenges in the field: providing an analytic foundation for the K41 statistical theory of turbulence and for the behavior of turbulent flows near instabilities and boundaries. A further aim is to explore rigidity phenomena and to attack several outstanding open problems in the context of differential inclusions, most prominently Morrey's conjecture on quasiconvexity and rank-one convexity.

Mots-clés : fluid mechanics,turbulence,compensated compactness,h principle,differential inclusions
Projet ERC : ENCATFLOW (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Improvements in both the economic effectiveness and environmental impacts to the fine chemical industry are necessary to maintain European competitiveness and reduce the global environmental cost of these products. Both of these goals can be accomplished by making existing processes more efficient. Catalysts facilitate the development of efficient chemical processes and are required for the sophisticated transformations used to produce high valued pharmaceutical and fragrance products. A process using catalysis requires significantly less energy, reactor volume, input feedstock and solvents in order to produce a desired material. However, the application of homogeneous catalysts for sophisticated transformations requires separating the product from the catalyst. Many separation processes are destructive to the catalytic material leading to limited use, driving the cost of the catalyst and the subsequent fine chemical processes. This separation limits reactor design to batch reactors, which are less efficient in terms of energy and solvents than flow type reactors. The EnCatFlow project will utilize encapsulated catalysts in a flow membrane reactor. This would uniquely offer both catalyst protection and recyclability in a flow reactor format unlike any currently developing technologies, allowing the development of novel commercially competing processes. Our team includes two industrial partners that have expertise in flow chemistry, catalyst development, and an expert from the Energy Research Centre of the Netherlands, next to the PI and the technical researcher. A envisioned process is discussed with PWF as the end-user. The final goal is to develop commercially competing processes and to start a spin off company to commercialise the technology.

Mots-clés : nature inspired catalysis
Projet ERC : STROMA (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 2386262.0 €

In 1984, Nossal wrote ‘‘A readership consisting of primarily anatomists has every right to question the favorite sport of research workers in cell immunology. This is to take a lymphoid tissue and totally destroy its beautiful and elaborately designed architecture to obtain simple cell suspension of lymphocytes, which are then asked to do more or less all the jobs of the original anatomic masterpiece’’. Growing evidence that lymph node (LN) stromal cells control the motility, activation and survival of lymphocytes has reinforced this view. These architectural cells assemble in 3D networks that regulate LN homeostasis and control its ability to remodel during inflammation. Understanding stromal cell biology is thus mandatory to our full comprehension of the immune system but this ambitious objective is technically challenging. As the complexity of the LN cannot be modelled in culture, knowledge gained from in vitro experiments is limited and will not address many relevant questions related to the biology of LN stromal cells, in particular (i) the elucidation of their origin and the precursor/product relationships that link them, (ii) the determination of their behavior in inflamed LNs and (iii) their subsequent fate in LNs that have returned to homeostasis. To this aim, I have developed several original, cutting-edge multicolor fluorescent reporter mouse models and computational modeling approaches to map the fate of single stromal cells and their progeny in situ. Using this innovative approach, my group will investigate the spatio-temporal behavior and molecular cues that orchestrate the development and dynamics of the major LN stromal cell populations in vivo, at steady state and under inflammatory conditions, at the single cell level. Because the proposed studies will unravel the precursor/product relationships linking the various stromal cell types, we anticipate to provide the first “Phylogenetic tree” of LN stromal cell development and remodeling.