Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SPECIPHIC (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
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 : 1499016.0 €

Optical microscopy has undergone a revolution that now allows us to access molecular resolution (“nanoscopy”) with the identification of specific biomolecules within biological samples. Nanoscopy has become a key approach to decipher the function of living matter since biomolecules are the elementary building blocks. While being a major tool, high-resolution and specificity can only be achieved by tagging the molecules of interest with fluorescent probes, which inevitably alters the samples, making them improper for medical applications including regenerative medicine. The leading dogmas being that (i) nanoscopy cannot be achieved without labelling and (ii) no specific signature from molecules can be retrieved without energy exchange with the sample (e.g. absorption by probes, molecular vibrational interaction). I propose a complete change of paradigm by introducing label-free nanoscopic imaging using the optical refractive index as a molecular sensor. My ground-breaking approach will be based on our pioneering work which demonstrates that phase, intensity and polarisation information can be quantitatively retrieved with unprecedented sensitivity and with an imaging resolution equivalent to regular imaging with fluorescent probes. I will re-forge this into a single-shot imaging technique capable of beating the optical resolution limit to access nanoscale resolutions, even deep inside living unmodified biological samples. Specific molecular information will be untangled through machine learning algorithms. SPECIPHIC will give birth to the first label-free molecular specific imaging with nanoscale resolution in pristine living biological tissues. The applicability of my concept will be demonstrated in this ERC starting project with applications in regenerative medicine and oncology, impacting thus directly important societal questions. My new approach will impact many other fields, in the biomedical world first but also in physics and for nanomaterial engineering.

Mots-clés : quantitative phase imaging,interferometry,label free imaging,optical microscopy,biological tissue imaging
Projet ERC : QOM3D (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Delft University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU Delft
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999594.0 €

Optomechanics is a field that aims to detect and control mechanical motion with light, ultimately at the quantum level. Experiments reaching the mechanical quantum ground state established optomechanics as a rapidly growing new field. Now that the quantum ground state has been reached, what is the next step? The current goal of the field is quantum superposition states of motion. An example of this is a mechanical “Schrodinger cat” state, in which a drum is in a quantum superposition of vibrating up and vibrating down at the same time. From a technological perspective, such states could be used as a memory for storage of quantum information, or as a quantum bit itself, performing quantum calculations with a mechanical object. From a fundamental perspective, Schrodinger cat states could be used to explore the limits of macroscopic quantum mechanics and to look for the boundary between the quantum and classical worlds. Despite their recent success, the coupling between light and motion in current implementations is too weak to achieve non-classical motion. Here, I propose a new optomechanical system coupling the motion of a millimeter-sized membrane to quantum microwave “light” in a three-dimensional superconducting cavity. In this new system, I will use the exceptional coherence photons in 3D cavities to strongly enhance the coupling of light and motion. To demonstrate the feasibility of this idea, I present preliminary data from a proof-of-concept device with coupling that is already close to state-of-the-art, with an outlook to scaling significantly beyond implementations shown to date. With the team funded by this project, I will implement these feasible but challenging steps, creating a system with optomechanical coupling that can potentially reach the strong coupling regime for a single photon. Using this new strong coupling, I will bring optomechanics to a new regime where one can create and explore quantum superpositions of massive, macroscopic objects.

Mots-clés : optomechanics,strong coupling,macroscopic quantum states,superconducting cavities,foundations of quantum mechanics,hybrid systems
Projet ERC : Rethyming (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 133333.33 €

Organ transplantation has revolutionized medicine as it became possible to replace an irreversibly diseased organ. However, the immune suppressive therapy to avoid rejection is associated to life-threatening complications. Finding a way to selectively induce tolerance to donor antigens, while maintaining immunity to pathogens and cancer antigens would represent a major breakthrough in medicine with the achievement of immunosuppression-free organ transplantation. During development and early life immune T cell competence and central tolerance are specified in the thymus; thus I aim to dissect the complexity of this organ by rebuilding it in a controlled fashion ex vivo. In a first step, a natural scaffold will be prepared from fresh human and animal thymi by perfusion decellularization; subsequently cultivated human thymic epithelial cells (TECs) will be used for re-epithelialization of the a-cellular scaffolds. Finally, immature lymphocytes from an HLA-mismatched donor will be delivered to the thymus-scaffolds through the preserved vascular extracellular matrix structures and cultured in a customized bioreactor in optimized conditions for T cell differentiation and tolerance induction. Detailed phenotypic and functional analyses will be performed to identify the frequency of mature T cell subsets, including Tregs, and assess the level of tolerance to the HLA antigens expressed by TECs. Finally, the possibility of re-epithelializing scaffolds with pig TECs will allow testing its interaction in vivo in the context of organ transplantation, providing the very first proof of principle that it may be possible to achieve antigen-specific tolerance and avoid rejection without the need for generic immunosuppressive therapy. Overall, this project takes a multidisciplinary approach to the study of tolerance by combining stem cell biology, bioengineering technologies, a deep knowledge of immunity and tolerance mechanisms in transplantation for a rapid clinical translation.

Mots-clés : bioengineering
Projet ERC : TAaGC (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

Organisms utilize several mechanisms to compensate for the damaging consequences of genetic perturbations. One such mechanism is the newly identified process of transcriptional adaptation (TA): in this process, certain deleterious mutations trigger the transcriptional modulation of so-called adapting genes. In some cases, e.g., when one of the upregulated genes is functionally redundant with the mutated gene, TA leads to functional compensation. Notably, unlike other modes of compensation, TA is not triggered by the loss of protein function. This unexpected observation has prompted studies into the machinery of TA and the contexts in which it functions. Following our discovery of TA (Rossi et al., 2015), we have shown that in zebrafish embryos and mouse cell lines, mutant mRNA degradation triggers this process (El-Brolosy et al., 2019). We also observed TA in C. elegans and found that small RNA biogenesis, in addition to mutant mRNA degradation, is required for this process (Serobyan et al., 2020). While these and other studies have documented the importance of TA and its occurrence across phylogenetically distant organisms, several key questions remain in terms of how TA arises and how prevalent it is. In this proposal, we aim to investigate the mechanisms that underlie TA, including 1) what determines which genes are targeted as adapting genes during TA, and 2) how the expression of these genes is modulated during TA. These studies will be carried out in zebrafish, C. elegans, mice, and multiple mouse and human cell lines, capitalizing on the genetic and biochemical approaches available in each model system, while simultaneously allowing us to analyze the conservation of the mechanisms underlying TA. In addition, we will investigate the relevance of TA in human health and disease. Ultimately, this work will further our understanding of the mechanisms that modulate genetic and phenotypic robustness in humans.

Mots-clés : transcriptional adaptation,genetic compensation,robustness,zebrafish,c elegans,mouse,human,small rnas,mutant mrna degradation
Projet ERC : CLEAN (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Bocconi University — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1770838.0 €

Organized crime is systematically associated with lower economic development and higher corruption, political instability and political violence across countries. However, causal evidence on the economic and political effects of organized crime remains limited. The present proposal advances our knowledge of organized crime in two main directions. First, I will explore the effects of organized crime on the allocation and effectiveness of public spending, focusing on two important areas of government spending: public procurement and public subsidies to private firms. This analysis will advance our knowledge of the practices through which captured politicians can distort the allocation of resources in favour of criminal organizations, their implications for the efficiency of government intervention, and the effectiveness of alternative policy responses. Second, whilst previous research has focused almost exclusively on the traditional areas of origin of criminal organizations, I will study the effects of criminal groups moving to new regions and countries. I will focus in particular on three different contexts: i) the “transplant” of criminal organizations from southern to northern Italian regions; ii) interactions of immigrants and natives in criminal activity in the wake of recent migration to the Netherlands; and iii) the inflow of members of the Sicilian Mafia into the US during the period of alcohol prohibition (1920-1933). The present proposal will advance our understanding of how criminal groups can relocate to new regions and countries; their interactions with the criminal groups that may already be present there; and the economic and social effects in the areas of destination. From a methodological perspective, all projects will take advantage of unique micro-level data and state-of-the-art econometric methods for impact evaluation to provide clean evidence on causal relationships.

Mots-clés : organized crime,immigration,impact evaluation
Projet ERC : SIMBIONT (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : European Molecular Biology Laboratory — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1492803.81 €

Organogensis is the process by which multiple different cell types grow, differentiate and interact with each other (both molecularly and physically) to create large complex structures with integrated functions, such as the heart, brain or limb. Understanding this process has enormous potential impact, both scientifically and medically. The SIMBIONT project represents both a grand technical challenge, and a fundamental scientific question. The grand technical challenge is to build the first ever multi-scale computer model of mammalian organogenesis, specifically limb development. This purpose of the model is to help us address the deep scientific question: How are the complex interactions at multiple scales (genes, molecules, cells and tissues) coordinated so as to build a carefully constructed 3D organ? So far, computer modelling has helped to understand some of the pieces of this puzzle, eg. morphogen gradients, or control of tissue growth. However, putting multiple pieces together into a single multi-scale simulation remains a challenge. We will use the latest state-of-the-art quantitative data-generation techniques (including Tomo-Seq and OPTiSPIM), to gather 3D data at multiple levels: gene expression patterns, cell signaling, cellular growth rates, intercalation patterns, and global tissue movements. In parallel we will develop a new multi-scale modeling framework which can integrate this quantitative data, to simulate both the molecular patterning and the mechanical growth of the developing limb bud. Doing so will allow us to ask new systems-level questions about (i) the molecular control of organ shape, (ii) coordination of patterning and growth, and (iii) the multi-scale robustness of the system. We will test the key predictions of the model experimentally (both with mouse mutants, and in vitro perturbations). SIMBIONT will serve as an example for modeling other complex multicellular processes in the future, eg. tissue engineering and regenerative medicine.

Mots-clés : multiscale modelling,gene regulatory network,organogensis,dynamic modelling,morphogenesis,spatial transcriptomics,limb develoment,finite element modelling
Projet ERC : VESCEL (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : University of Twente — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2250000.0 €

Organs-on-chip hold great promise for the creation of complex and realistic disease models while having the potential to refine, reduce and (partly) replace existing animal models (3R principle). Of all organs, vasculature is extremely well-suited to realize on-chip since it pervades the whole organism, is present in all other organs, its malfunctioning plays a role in many diseases and finally is ideally suited to approach with microfabrication and microfluidic technologies. In the VESCEL program we propose the development of innovative technologies enabling the use of differentiated human induced pluripotent stem cells (hiPSC) to engineer blood vessels on chip that constitute realistic disease models for thrombosis and neurodegenerative (ND) diseases. The use of differentiated hiPSC allows the realization of blood vessels based upon patient-specific material, without the need for biopsies, while development of integrated microsensors for small molecules (pH, O2, NO) offers the possibility of on-line monitoring. To optimize the hiPSC differentiation conditions we propose the use of a microdroplet platform, that combines high-throughput capability (up to 1000 cells/s) with control of single cell microenvironment. We will also develop a new flexible technology for real 3D vasculature realization using advanced 3D printing technologies. These four innovative technology developments will be integrated in two biomedical applications to study two important classes of diseases, thrombosis and neurodegenerative (ND) diseases. For thrombosis we focus on the study of parameters such as blood pressure and stenosis as well as effects of drugs on thrombus formation, while for ND diseases study we will use a blood brain barrier (BBB) model to investigate nanoparticle and peptide transport across the BBB for a form of Alzheimer’s disease, as well as leukocyte extravasation for multiple sclerosis (MS).

Mots-clés : organ on chip,microfluidics,droplet microfluidics,sensing
Projet ERC : ALGOA (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : University of Eastern Finland — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UEF
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Osteoarthritis (OA) is a common joint disease affecting over 40 million Europeans. Most common consequences of OA are pain, disability and social isolation. What is alarming, the number of patients will increase 50% in developed countries during the next 20 years. Moreover, the economic costs of OA are considerable since 1) direct healthcare (hospital admissions, medical examinations, drug therapy, etc.) and 2) productivity costs due to reduced performance while at work and absence from work have been estimated to be between 1% and 2.5% of the gross domestic product (GDP) in Western countries. We have developed an algorithm that is able to predict the progression of OA for overweight subjects while healthy subjects do not develop OA. When employed in clinical use, preventive and personalised treatments can be started before clinically significant symptoms are observed. This marks a major breakthrough in improving the life quality of OA patients and patients prone to OA. Our discovery will directly lead to longer working careers and lesser absence from work, and will result subsequently increased productivity. Moreover, the patients are expected to live longer due to reduced disability and social isolation. Moreover, the discovery provides economic long-term relief for the health care system, which is burdened by increasing geriatric population and stringent economic environment. With our tool, as an example, by eliminating 25% of medical examinations annually due to overweight or obesity in Finland (150.000 patients), we estimate to decrease annual direct costs by 140M€ and indirect costs by 185M€. In the PoC project we will carry out technical proof-of-concept and perform pre-commercialisation actions to shorten the time to market. The ultimate goal after the project is to develop our innovation towards a software product, aiding the OA diagnostics in hospitals and having commercialisation potential amongst medical device companies.

Mots-clés : osteoarthritis,prediction,prevention,health economics,finite element modeling,image analysis,knee joint,medical imaging,healthcare,personalized medicine
Projet ERC : ArthroDUR (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Johannes Gutenberg University Mainz — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Osteoarthritis (OA) is the most common form of arthritis of the joints, affecting over 70 million EU citizens. At present, no cure for OA is available; only symptomatic therapies may help to ameliorate this painful disorder. OA affects the integrity of the cartilage and progresses to an increased damage in its surrounding tissues, inclusive bone, and to inflammation of the synovial tissue. The latter reaction is caused by an accumulation of bone splinters. The therapy of choice would be – if available – bidirectional: first, regeneration of the damaged cartilage (by implants) and second, dissolution of the bone fragments (by injections). This proposal presents for the first time this two-fold solution. Within my ERC Advanced Grant “BIOSILICA” (No. 268476) we disclosed that biosilica elicits morphogenetic activity in cells involved in connective tissue formation. The effect of silica is augmented by another natural inorganic polymer, by polyphosphate (polyP), which is synthesized in most animal cells, especially blood platelets that accumulate in damaged bone and cartilage. polyP acts as “metabolic fuel” for the synthesis of the extracellular inorganic and organic skeletal and cartilage tissues. Our strategy is to combine and to amplify the beneficial properties of these two polymers, biosilica and polyP, their morphogenetic activity with their structure-forming/guiding activity, by applying hybrid microparticles, consisting of silica and polyP. The proposed project will provide the proof-of-concept of this dual strategy, using silica and the amorphous Mg2+/Ca2+ salt of polyP together with hyaluronic acid, to dissolve firstly existing bone splinters in the synovial fluid (by injection), reducing the painful joint burden in osteoarthritis, and secondly to repair damaged cartilage with polyP/silica implants. This innovative material, injectable and implantable, will be developed to commercializable products for the benefit of the aging society.

Mots-clés : tissue engineering,cartilage,synovial fluid,osteoarthritis,regenerative medicine,degenerative joint disorder,biomedicine,biomaterials science,regenerative implants,biosilica,polyphosphate
Projet ERC : MUOTO (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Oulu — Pays : Finlande — Rôle : PI
Acronyme de l'entité : U. Oulu
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Osteoarthritis (OA) is the most common musculoskeletal disease. OA has significant socio-economic impact as it severely affects the quality of life, reduces productivity and carries higher risk of mortality. However, the development of new treatments for OA is painstakingly long and very challenging. There are many clinical OA drug trials that have ended in a failure. In my ERC-StG project, we have developed 3D histopathological evaluation method of OA from micro-computed tomography (μCT). It allows detecting narrow cracks and surface irregularities that are associated with very early OA. Importantly, with our novel method deterioration and degradation of joint surfaces can be analysed much earlier than with any other non-invasive imaging solution. The key is in pinpointing the most important histological changes with the highest reliability while retaining the anatomical information, lost in the conventional histology. This is expected to decrease the number of histological evaluations by 20-fold, saving substantial amount of time, and consequently, money. We will significantly add value to pharmaceutical industry developing new therapies for OA. Eventually, our solution speeds up the time-to-market for new and more effective OA drugs, while saving in R&D costs. Later on, we can offer inexpensive, effective and accurate diagnosis and prognosis tool for OA patients. Gradually, we will gather a big data repository of various compounds and their effects on OA. From this data, and with the help of Artificial Intelligence engine, we can visually show the predicted compound efficacy, or suggest a drug combination never imagined earlier. In this PoC, the commercialization planning is carried out with a focal point on Software as a Service (SaaS) business model. We will also improve the adoptability of our innovation (e.g. visualisation of the OA severity, positioning in the value chain) and plan the big data business strategy.

Mots-clés : osteoarthritis,histopathology,preclinical models,articular cartilage degeneration,software as a service