Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CULTIVATE MSS (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1787114.1 €

CULTIVATE MSS aims to assess the significance of the trade in medieval manuscripts for the development of ideas about the nature and value of European culture in the early 20th century, a crucial period for the development of modern European nation states. Although recent technological developments have facilitated quantitative analyses of provenance data, charting in increasing detail the early-20th-century movement of manuscripts, including an exodus of works to America, qualitative analyses have failed to keep pace, leaving questions of how and why particular books were valued underexplored. The PI’s role in the development of the Schoenberg Database of Manuscripts, which has begun to make available historic data about books, has revealed the need for a reassessment of the relationship between collecting and scholarship, and the potential for existing data about the manuscript trade to be used, with unpublished archival sources, to identify and compare the economic and philosophical values projected onto books. Thus the project uses the PI’s expertise to develop a multi-disciplinary approach to assess the roles of collectors, scholars and dealers in the formation of collections of medieval manuscripts, and the impact of this on scholarship, comparing the English-speaking world, France and Germany. It will analyse published and unpublished accounts of manuscripts, together with price data, to reconstruct values projected onto books. It will seek to contextualise these values within the history of the early 20th century, assessing the impact of two world wars and other political and economic shifts on the trade in books and attitudes to manuscripts as objects of national significance. The Middle Ages are often identified with the emergence of European cultural identities, thus a reappraisal of the historiography of the study of medieval manuscripts has the potential to impact research about attitudes to European culture and identity in a wide range of disciplines.

Mots-clés : medieval manuscripts,provenance history,historiography,collecting,twentieth century book trade
Projet ERC : StopWaste (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Helmholtz Zentrum München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HMGU
Type d'entité : Recherche
Financement ERC de l'entité : 1411051.0 €

Cachexia is the deadly outcome of many late stage cancers. It is characterized by severe wasting of adipose tissue and muscle mass, cardiac dysfunction and systemic inflammation. To date, no prognostic biomarker or efficient treatment against wasting is available, and ultimately 30% of all patients with cancer will die of cachexia. Hence, we have the critical unmet and urgent medical need of developing novel biomarkers and treatment options. Until now, research has focused on targeting either tumor-derived secreted proteins or specific aspects of organ dysfunction such as muscle atrophy. StopWaste builds on recent advances of my group in targeting adipose tissue malfunction in cachexia. My current data support the new concept that tumors activate futile substrate cycling in adipocytes, which leads to an energy crisis that drives systemic metabolic dysfunction. Interestingly, similar to obesity, perturbed adipose tissue in cachexia causes the increased release of bioreactive signaling lipids such as C16:0 ceramides which appear before any wasting occurs. My recently established state-of-the-art multi-omics workflow to trace substrate cycling paired with the functional and clinical readouts of cachexia present in my lab now enable me to identify the molecular origin of these cycles and their impact on systemic metabolism. Using my established cell culture systems and multiple cachexia mouse models as well as patient samples, I will investigate (1) the origin of the altered circulating lipids and their potential as early cachexia biomarkers, (2) if they derive from perturbed adipocytes by futile cycling, and (3) if they drive insulin resistance which, in combination with the as-yet unknown tumor-islet axis I have identified, aggravates catabolism by lack of insulin anabolic signaling. In summary, StopWaste addresses the interplay of glucose and lipid metabolic pathways that lead to cachexia, providing for the first time a holistic signature of wasting metabolism.

Mots-clés : metabolism,cancer cachexia,adipose tissue,lipids,beta cells
Projet ERC : WipeOutFear (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Acronyme de l'entité : KUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Can fear memories be erased from the brain? While it sounds like science fiction, recent findings suggest that fear memories can be undone upon their retrieval, through either pharmacological or behavioural interventions. Still, whether such reconsolidation interference techniques genuinely result in permanent erasure of the original fear memory is a topic of considerable controversy. Purely behavioural work may never settle the debate, as it cannot be excluded that an apparent loss of fear memory reflects a long-lasting failure to retrieve the fear memory rather than its permanent erasure. We argue that a careful look at the brain memory circuits that control the reduced expression of fear after reconsolidation interference, through imaging studies in humans and inactivation studies in rats, does have the potential to resolve the controversy and decide between erasure and retrieval failure as mechanisms underlying reconsolidation interference [WP1]. To open up a memory trace for reconsolidation interference, it is important that retrieval of the memory is accompanied by surprise or prediction error (PE; a discrepancy between the memory and what actually happens), as we demonstrated in a break-through study in Science (Sevenster, Beckers, & Kindt, 2013). Here, we propose that subtle differences in the degree of PE generated during fear memory retrieval may be what demarcates memory erasure from impaired retrieval. To investigate that claim, we will pioneer an objective neural marker of PE in humans [WP2] and use optogenetics to directly trigger dopamine-based PE signals in the rat brain in order to establish the causal role of PE in enabling fear memory erasure. Along the way, we will investigate the generalization of fear to novel cues as both a problem and a potential target for fear memory modification [WP3] and test an innovative method to interfere with reconsolidation that circumvents limitations of current pharmacological and behavioural techniques [WP4].

Mots-clés : learning and memory,behavioural neuroscience,experimental psychopathology
Projet ERC : CartiLube (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 598886.0 €

Can we exploit insights from the remarkably lubricated surfaces of articular cartilage, to create lubricants that may alleviate osteoarthritis (OA), the most widespread joint disease, affecting millions? These, succinctly, are the challenges of the present proposal. They are driven by our recent finding that lubrication of destabilised joints leads to changes in gene-regulation of the cartilage-embedded chondrocytes to protect against development of the disease. OA alleviation is known to arise through orthopedically suppressing shear-stresses on the cartilage, and a central premise of this project is that, by reducing friction at the articulating cartilage through suitable lubrication, we may achieve the same beneficial effect on the disease. The objectives of this project are to better understand the origins of cartilage boundary lubrication through examination of friction-reduction by its main molecular components, and exploit that understanding to create lubricants that, on intra-articular injection, will lubricate cartilage sufficiently well to achieve alleviation of OA via gene regulation. The project will examine, via both nanotribometric and macroscopic measurements, how the main molecular species implicated in cartilage lubrication, lipids, hyaluronan and lubricin, and their combinations, act together to form optimally lubricating boundary layers on model surfaces as well as on excised cartilage. Based on this, we shall develop suitable materials to lubricate cartilage in joints, using mouse models. Lubricants will further be optimized with respect to their retention in the joint and cartilage targeting, both in model studies and in vivo. The effect of the lubricants in regulating gene expression, in reducing pain and cartilage degradation, and in promoting stem-cell adhesion to the cartilage will be studied in a mouse model in which OA has been induced. Our results will have implications for treatment of a common, debilitating disease.

Mots-clés : boundary lubrication,biological lubrication,cartilage friction and lubrication,biolubrication and mechanotransduction,osteoarthritis,cartilage lubrication and gene regulation
Projet ERC : QEWS (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Dutch Research Council — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : NWO
Type d'entité : Recherche
Financement ERC de l'entité : 2495485.0 €

Can we shape an electron wavepacket in space and time? Can we tailor it to probe material properties that are currently inaccessible? Recent work has shown that high-energy electrons (80-200 keV) interacting with strong light fields can absorb or release quantized energy packets equal to the photon energy. This dresses the electron into a superposition state composed of a spectrum of energy-loss and -gain sidebands. Here we exploit this Photon-Induced Near-field Electron Microscopy (PINEM) effect in order to create a revolutionary new method of tailoring the spatial and temporal distribution of electron wavepackets at will. Building on my strong expertise in the field of electron-light-matter interactions and nanophotonics, we will incorporate the PINEM effect into a scanning electron microscope (SEM) and integrate it with advanced cathodoluminescence (CL) light detection. Using 5 keV electrons and advanced optical metamaterial designs we will amplify the PINEM effect by a factor 1000. Using spatial light modulation we spatially vary the PINEM light fields which results in wide control over the electron energy spectrum. We create electron-metasurface interactions that stretch, chirp, or split the electron wavepacket, enabling entirely new ultrafast pump-probe detection schemes of optical excitations and relaxations. Using a compact solid-state implementation we perform subsequent PINEM operations on a single electron and perform a full quantum state reconstruction of the electron’s density matrix that represents the interaction. We derive the wavepacket amplitude and phase and reveal dephasing processes in optical excitations. The new PINEM-SEM-CL technique opens up an entirely new world of electron microscopy applications in integrated optics, nanophotonics, and opto-electronics and will provide detailed insights into fundamental electron-light-matter interactions that have been inaccessible thus far.

Mots-clés : quantum electron wavepackets,photon induced near field electron microscopy,near field optics,metamaterials,cathodoluminescence
Projet ERC : SIRIUS (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499290.0 €

Cancer and bacterial infections are projected to kill 18 million people worldwide annually by 2050. Fast and reliable diagnostics are essential for early and targeted treatments. Microfluidics is at the heart of the miniaturisation of diagnostics, enabling novel portable and low-cost point-of-care devices. Inertial particle microfluidics (IPMF) is a novel and competitive method with applications in cancer cell and bacteria separation. Yet, the physics behind IPMF is not well understood, making progress slow and costly. Novel design rules are in urgent need to avoid trial-and-error experiments. I will numerically investigate the underlying physical mechanisms and develop the first predictive toolkit for engineering applications of IPMF. In particular, I will address five ambitious challenges in SIRIUS: 1. Develop an accurate numerical model for IPMF. 2. Understand the impact of particle softness. 3. Investigate the effect of finite particle concentration. 4. Improve the currently low separation efficiency of small particles. 5. Develop a toolkit to enable simulation-driven design. These objectives are feasible through novel numerical approaches based on the lattice-Boltzmann method and state-of-the-art high-performance computing. SIRIUS will pursue an innovative simulation campaign, validated with existing experimental data, to generate both physical insight and scaling laws for simulation-driven design. For the first time, SIRIUS will produce robust numerical methods for IPMF. My pioneering research will uncover the physics behind particle separation and culminate in a design toolkit for IPMF engineers. SIRIUS will fill a critical gap and open up an entirely new research field: “Simulations for inertial particle microfluidics”. Results of SIRIUS will be published as open-source codes, open-access articles, and open data. This will ultimately enable faster, less costly and more innovative research in the field of microfluidics for diagnostics.

Mots-clés : particle separation,simulation driven design,inertial microfluidics,lattice boltzmann method,fluidic devices,suspensions
Projet ERC : XMED (Horizon 2020, appel 2014, Proof of concept grants)
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 : 149851.0 €

Cancer detection at an early stage is crucial for subsequent therapy success. To achieve this goal, an effective screening should rely on a specific tool that should be not only non-invasive but also adaptable to patients and their diseases. Widely used nowadays, X-Ray imaging (RX) is a well-established cancer screening technique. However, it poses major problems of (i) detection of tumours at early stages when they are small and of low contrast, (ii) dose deposition in a body, especially for frequent and long term monitoring and (iii) energy tunability of the X-ray source to optimize the imaging. The project XMED aims at tackling simultaneously these three strong limitations, and to come out within 18 months with a demonstrator. For this purpose the most advanced electron beams produced by laser plasma accelerators will be use to radiate a bright, tunable X ray beam using the recent all optical Compton scheme.

Mots-clés : medical imaging,x ray,screening,tomography,laser,plasma,accelerator,ultrafast,murine,startup
Projet ERC : CHEMCHECK (Horizon 2020, appel 2015, Starting 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 : 1500000.0 €

Cancer evades the immune system by generating an immunosuppressive tumour-microenvironment through various mechanisms to enable unhampered growth. Recent breakthroughs in blocking one of these mechanisms – the so called ‘immune checkpoints’ – put cancer immunotherapy back in the spotlights. Although promising, clinical benefits of these checkpoint inhibitors as single treatment has been limited to a subset of patients and goes along with unwanted systemic autoimmune toxicity. I hypostasize, that attacking the tumour microenvironment from multiple immunological angles simultaneously by local, conditional, and multimodal immunomodulation will greatly improve success of cancer immunotherapy and patient wellbeing. To achieve this, I will develop a highly defined synergistic chemistry-based molecular therapeutic toolbox to specifically attack cancer, acting on effector T cells, macrophages as well as tumour cells simultaneously. In this highly multidisciplinary endeavour I will (i) generate novel multifunctional dendritic cell targeted anti-cancer vaccines to ‘educate’ the patient’s immune system to recognise the tumour, (ii) I will develop conditional, targeted immune checkpoint inhibitors to release the immunosuppressive break specifically within the tumour microenvironment without the risk of autoimmunity and (iii) I will generate chemical tools to locally eliminate the tumour-associated macrophages to tear down a major immunosuppressive barrier. I will do so utilizing the novel ModimAb technology which I developed to obtain functionalized antibody fragments. These individual therapeutic tools will allow me and my research team to explore uncharted tumour immunological territories in vitro as well as in vivo, greatly advancing the field of cancer immunotherapy. But above all, together they will form a highly dedicated symbiotic immunotherapeutic regime which will be extremely effective without systemic side effects, dramatically improving patient care.

Mots-clés : cancer immunotherapy,chemical biology,tumour microenvironment,immune checkpoint,antibody engineering
Projet ERC : COLGENES (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498618.0 €

Cancer genome sequencing has led to a paradigm shift in our understanding of oncogenesis. It has identified thousands of genetic alterations that segregate into two groups, a small number of frequently mutated genes and a much larger number of infrequently mutated genes. The causative role of frequently mutated genes is often clear and are the focus of concerted therapeutic development efforts. The role of those infrequently mutated is often unclear and can be difficult to separate from ‘mutational noise’. Determining the relevance of low frequency mutations is important for providing a full understanding of processes driving tumourigenesis and if functionally relevant may have broader implications on the applicability of targeted therapies. This project aims to begin addressing this by defining the function of all genes mutated in colorectal cancer (CRC) in the earliest stages of tumour formation. I have performed a whole genome screen in a 3D organoid CRC initiation model identifying several potentially important mediators of this process. Crucially, some of these genes are mutated in CRC at low frequency but not described as cancer driver genes. Thus, I hypothesize that rather than ‘mutational noise’ infrequently mutated genes contribute to CRC initiation. I will test this by addressing two aims: 1) Determine the role of genes mutated in CRC during tumour initiation 2) Validate and determine the function of a subset of identified genes potentially defining novel cancer mechanisms I will use a combination of CRISPR genetic disruption in state-of-the-art 3D mouse and human organoid cultures and advanced mouse models to address these aims. This comprehensive approach will provide a foundation for understanding the importance of the entire spectrum of mutations in CRC and open new avenues of research into the function of these genes. More broadly, it has the potential to make a profound impact on how we think about tumourigenic mechanisms and cancer therapeutics.

Mots-clés : colorectal cancer,cancer gene identification
Projet ERC : DynaCOMP (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : University of Patras — Pays : Grèce — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Cancer is a major clinical, societal and economic burden worldwide and development of novel anti-cancer therapies constitutes a major investment of public and private funds. Despite intense research over decades however, which has led to a much improved understanding of cancer biology, cancer treatment remains a challenge. This is to a large extent due to the genetic heterogeneity of cancer and the ability of cancer cells to escape treatment by constantly undergoing further genetic alterations. During our ERC funded work, we have shown that aberrations in the DNA replication licensing pathway may contribute to the genome plasticity of cancer cells, and appear a common feature of cancer cells. They may however also constitute an Achilles foot, as cancer cells appear more dependent on negative regulators of the licensing system for survival. Cancer cells may therefore be more sensitive than normal cells to compounds targeting this control (inhibition of untimely licensing). We have identified compounds which target the DNA replication licensing inhibitor Geminin. The proposed PoC study will enable us to: - assess the efficacy and specificity of the identified compounds in cells and preclinical models and study their mechanism of action. - investigate the potential use of these compounds for studying cell cycle processes. - assess whether the functional imaging approaches developed under the mother ERC project, which quantify protein-protein interactions within living cells, may constitute a powerful tool for in-cell analysis of novel lead compounds. The project thus aims to characterize, protect and commercialize novel putative anti-tumor agents as well as the in-cell methods developed for their characterization.

Mots-clés : anti tumour drug,bioactive compounds,dna replication licensing,synthetic lethality,functional imaging,cell based assays,cancer