Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ScoliStorm (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 919062.5 €

Adolescent idiopathic scoliosis (AIS) is a 3D deformity of the spine affecting previously healthy children, substantially reducing their quality of life and creating a life-long burden of disease. Although it has been indentified since the time of Hippocrates (400 BC), we have not been able to rationally develop effective treatments and provide a cure for these children suffering from AIS because its cause and mechanism of disease are still unknown. ScoliStorm will create a paradigm shift in AIS research by uncovering its complex perfect storm of anatomical, biomechanical and mechanobiological causes in the intervertebral disc and exploring this disease mechanism whereby predictive triggers are identified that can be used for prevention and early treatment. We will study human subjects non-invasively through disease initiation and progression, creating for the first time a comprehensive dataset of healthy and scoliotic human spines that can be used for early detection and treatment of juvenile spine conditions. We will create safe non-radiographic accurate imaging of the osseous spine, available in most hospitals, which can become the standard for diagnosis and monitoring of osseous injury and disease in juveniles. We will develop high-throughput creation and use of subject specific in silico models, allowing simulation of organ and tissue function such that morphological imaging data can provide functional analysis of the patient for diagnosis and treatment. Mechanisms affecting tissue adaptation will be mapped and show that normal processes by their coincidence can create an aberrant response and disease, providing an explanation applicable for other multifactorial diseases. Thus, a unique dedicated and complete multidisciplinary process, combining 1) bioengineering analysis, exploiting imaging, in silico modeling, in vitro and ex vivo approaches in humans, and 2) clinical medicine, also applicable for exploring other multifactorial diseases, will be created.

Mots-clés : scoliosis,aetiology,intervertebral disc,growth,biomechanics,mechanobiology,synthetic ct
Projet ERC : TIL-FIT (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Università della Svizzera italiana — Pays : Suisse — Rôle : PI
Acronyme de l'entité : USI
Type d'entité : Recherche
Financement ERC de l'entité : 1406250.0 €

Adoptive T cell therapies (ACTs) are emerging as a promising strategy to treat cancer. Tumor-infiltrating lymphocytes (TILs) are expanded ex vivo, selected for recognition of neoantigens, further expanded and then infused back into patients. This procedure requires extensive culturing and expansion of TILs during which many T cell clonotypes are lost. As tumor-reactive TILs are often exhausted and tend to be overgrown by functional, non-specific T cells in culture, the chance to identify potent tumor-reactive T cells dramatically decreases. Moreover, extensive expansion of T cells diminishes their anti-tumor activity and persistence in the body after adoptive transfers. Thus, improving the fitness of T cells is crucial to increase the success rate of ACTs and make this therapy accessible to a broad spectrum of cancer patients. Our first aim is to increase the fitness of T cells by designing metabolic and pharmacological interventions based on proteomic profiles of TILs from patients with liver cancer. Second, we will use machine-learning algorithms for the extraction of signatures to predict whether TILs grow well in culture, require and respond to metabolic interventions, or cannot be revitalized and do not grow at all. To deal with non-growing T cells, we aim at establishing a microfluidics-based workflow to graft the entire T cell receptor (TCR) repertoire from thousands of non-growing TILs onto fast growing Jurkat cells. After selecting Jurkat cells that recognize neoantigens, their TCRs will be expressed on naïve T cells obtained from the patient’s blood that are fit and suitable for ACT. This project will contribute to a better understanding of the T cell response to liver cancer and help increasing the success of personalized ACTs for solid tumors.
Projet ERC : ReCaP (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Royal College of Surgeons in Ireland — Pays : Irlande — Rôle : PI
Acronyme de l'entité : RCSI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2999410.0 €

Adult articular cartilage has a limited capacity for repair and when damaged or injured, experiences a loss of function which leads to joint degeneration and ultimately osteoarthritis. Biomaterials-based treatments have had very limited success due to the complex zonal structure of the articular joint, problems with biomaterial retention at the joint surface and achieving integration with the host tissue while also maintaining load bearing capacity. Stem cell therapies have also failed to live up to significant hype for a number of reasons including the challenges with achieving formation of stable hyaline cartilage which does not undergo hypertrophy. Building on a wealth of experience in the area, we propose a solution. ReCaP will initially overcome the problems with traditional biomaterials approaches by utilising recent advances in the area of advanced manufacturing and 3D printing to develop a 3D printed multi-layered scaffold with pore architecture, mechanical properties and bioactive composition tailored to regenerate articular cartilage, intermediate calcified cartilage and subchondral bone. Following this, and building on internationally recognised pioneering research in the applicant’s lab on scaffold-mediated nanomedicine delivery, this system will be functionalised for the controlled non-viral delivery of nucleic acids (including plasmid DNA and microRNAs) to direct host stem cells to produce stable hyaline cartilage at the joint surface and encourage the rapid formation of vascularised bone in the subchondral region. A new paradigm-shifting surgical procedure will then be applied to allow this system to be anchored to the joint surface while directing host cell infiltration and tissue repair, thus promoting restoration of even large regions of the damaged joint through a joint surfacing approach. The proposed ReCaP platform is thus a paradigm shifting disruptive technology that will revolutionise the way joint injuries are treated.

Mots-clés : biomaterial,scaffold,manufacturing,cartilage,bone,3d printing,gene delivery,stem cells
Projet ERC : PRELICAN (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Université de Strasbourg — Pays : France — Rôle : Partner
Acronyme de l'entité : UNISTRA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

Advanced liver disease and cancer is the only major cause of death still increasing each year. Major causes include hepatitis B and C viruses, alcohol and non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH). A major contributing factor to the increasing incidence and mortality of liver disease is the staggering rise in obesity. The absence of effective therapeutic options for NAFLD/NASH, advanced liver disease and cancer contribute to the poor prognosis and the high cost associated with patient care. We have established a tractable and clinically relevant human cell-based model system in which viral infection, ethanol or free fatty acids induce a clinical gene expression signature robustly predicting liver disease progression and long-term HCC risk in cirrhotic patients. Using this model we identified compounds as HCC chemopreventive agents. Aiming to evaluate these compounds for future clinical development and potential commercialization we will perform proof-of-concept studies in state-of-the-art mouse models for NASH and hepatocarcinogenesis. Specifically we will assess the therapeutic effect on liver inflammation, steatosis, fibrosis and HCC development and investigate its safety in long-term administration. With the completion of this program we expect to obtain a robust proof-of-concept data package as a first- or best-in-class compound for treatment of chronic liver disease and prevention of HCC.

Mots-clés : liver disease,nafld,nash,antibody,drug development,animal model,steatosis,fibrosis,liver cancer,hepatocarcinogenesis
Projet ERC : FIBCAN (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : The University of Texas System — Pays : Etats-Unis — Rôle : Partner
Acronyme de l'entité : UT System
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 305000.0 €

Advanced liver diseases such as cirrhosis and hepatocellular carcinoma (HCC) are major challenges for global health. HCC is the second leading and fastest rising cause of cancer death worldwide. Viral and metabolic liver disease are the main risk factors for HCC, which nearly always arises in advanced liver fibrosis. For metabolic liver disease approved therapies are absent. Cure or suppression of viral infection cannot eliminate the HCC risk in patients with advanced fibrosis. Despite significant progress, therapeutic options for established HCC are still limited in efficacy and safety. Importantly, patient survival in HCC is dependent on the underlying fibrotic liver disease which is not targeted by approved HCC therapies. Addressing these unmet medical needs, FIBCAN aims to identify urgently needed targets for prevention and treatment of fibrosis-driven liver cancer. A key focus of FIBCAN will be the investigation of Claudin-1 as a previously undiscovered target for prevention and treatment of fibrosis-driven HCC. Our own data obtained in patient-derived model systems and tissues provide solid evidence that Claudin-1 is implicated in liver fibrosis and hepatocarcinogenesis, and overall and liver-specific patient death. To discover novel targets, we will apply a liver disease discovery platform modeling the clinical cell circuits of cirrhotic patients progressing to HCC combined with single cell RNA-seq and spatial transcriptomics of patient tissues. Proof-of-concept studies of target-specific compounds combined with biomarker discovery in cutting-edge patient-derived model systems will deliver novel strategies for further clinical development. A strong collaboration with pharma will lead to rapid translation of the FIBCAN program into the clinic. By delivering urgently needed therapeutic strategies for advanced liver disease and HCC, this proposal will have a marked impact on the management and outcome of patients with advanced liver disease in Europe and beyond.

Mots-clés : liver disease,liver cancer,hepatitis c,hepatocellular carcinoma,cellular pathways,kinases,phosphatases,viral hepatitis,drug target,biomarker,cell circuits
Projet ERC : Time2Life (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Spectroswiss (Switzerland ) — Pays : Suisse — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 150000.0 €

Advances in biotechnology, pharmaceutical and life sciences require improved performance of even the most powerful analytical techniques to target the extreme complexity of modern biological samples. Due to its high performance, Fourier transform mass spectrometry (FTMS) is the central analytical technique in biomolecular analysis. Fourier transform (FT) drives FTMS by converting the time-domain (transient) data to mass spectra which, in turn, provide the biological information. Although FT is robust, it is inherently slow due to its strict uncertainty principle. Thus, many life sciences applications of FTMS are suffering from a limited throughput – data acquisition in FTMS should be done faster! Recent innovation results of our ERC Starting Grant “Super-resolution mass spectrometry for health and sustainability” have revealed the incredible power that methods of advanced signal processing, whose uncertainty principles are less strict than the FT one, have to offer to the everyday routine high-performance FTMS. Thus, we have rationally implemented existing and developed novel super-resolution and advanced signal processing methods to substantially speed up FTMS. While fundamental and technical feasibilities of our approach have been evaluated favorably at the lab level, turning these research outputs into a commercial proposition is yet to be demonstrated. Therefore, the aim of Time2Life is to translate our technology validated in lab into a robust industry-grade technology that accelerates high-performance biological mass spectrometry via the advanced signal processing of time-domain (transient) data and thus leverages life sciences applications. The industrial and academic end-users would be able to identify and quantify more analytes (e.g., peptides, proteins and metabolites) and thus enhance biological significance and accuracy of their research and clinical work. Notably, we target the unrepresented by SME area of time-domain data analysis in mass spectrometry.

Mots-clés : mass spectrometry,fourier transform mass spectrometry,signal processing,super resolution signal processing,proteomics,metabolomics,life sciences
Projet ERC : AEROFLEX (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Office national d’études et de recherches aérospatiales — Pays : France — Rôle : PI
Acronyme de l'entité : ONERA
Type d'entité : Recherche
Financement ERC de l'entité : 1377290.0 €

Aeroelastic instabilities are at the origin of large deformations of structures and are limiting the capacities of products in various industrial branches such as aeronautics, marine industry, or wind electricity production. If suppressing aeroelastic instabilities is an ultimate goal, a paradigm shift in the technological development is to take advantage of these instabilities to achieve others objectives, as reducing the drag of these flexible structures. The ground-breaking challenges addressed in this project are to design fundamentally new theoretical methodologies for (i) describing mathematically aeroelastic instabilities, (ii) suppressing them and (iii) using them to reduce mean drag of structures at a low energetic cost. To that aim, two types of aeroelastic phenomena will be specifically studied: the flutter, which arises as a result of an unstable coupling instability between two stable dynamics, that of the structures and that the flow, and vortex-induced vibrations which appear when the fluid dynamics is unstable. An aeroelastic global stability analysis will be first developed and applied to problems of increasing complexity, starting from two-dimensional free-vibrating rigid structures and progressing towards three-dimensional free-deforming elastic structures. The control of these aeroelastic instabilities will be then addressed with two different objectives: their suppression or their use for flow control. A theoretical passive control methodology will be established for suppressing linear aeroelastic instabilities, and extended to high Reynolds number flows and experimental configurations. New perturbation methods for solving strongly nonlinear problems and adjoint-based control algorithm will allow to use these aeroelastic instabilities for drag reduction. This project will allow innovative control solutions to emerge, not only in flutter or vortex-induced vibrations problems, but also in a much broader class of fluid-structure problems.

Mots-clés : aeroelasticity,vortex induced vibrations,global stability analysis,adjoint based control
Projet ERC : CHAPAs (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Helsinki — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999704.0 €

Aerosol particles affect the climate by scattering incoming radiation and by acting as cloud condensation nuclei; however, their net effect remains of highest uncertainty, specifically when quantifying their relationship to anthropogenic greenhouse gases. It has been estimated that 45% of the variance of aerosol forcing arises from uncertainties in natural emissions. This highlight the importance of understanding pristine preindustrial-like environments, with natural aerosols only. One of the great challenges in understanding preindustrial aerosols and their sources resides in identifying the processes by which new particles form and grow from oxidized vapours. We recently presented in Science the ground-breaking observation of purely organic nucleation. The existence of this mechanism was confirmed by laboratory experiments where we show that highly oxygenated molecules are able to form new particles independent of H2SO4. This finding sheds the light into the preindustrial era where the anthropogenic emissions were almost absent and H2SO4 concentration was rather minimal. The aim of my project is to provide unprecedented data to resolve the preindustrial nucleation mechanism. I will organize intensive long-term measurements in pristine preindustrial-like environments like the Arctic and Siberia. Using state-of-the-art chemical ionization mass spectrometry, I will retrieve the chemical cluster composition and the vapours concentration. Additionally, I am planning short intensive measurements at high altitude above the oceans. Finally, these measurements will be complemented by laboratory experiments needed to probe the observed mechanism and retrieve a parametrization that can be used in global modelling. The outcome of these field campaigns combined with laboratory experiments will provide extraordinary results in understanding pre-industrial aerosol formation, which will set the baseline for estimations of the impact of present and future aerosol on climate.
Projet ERC : NEURAMORPH (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : RWTH Aachen University — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : RWTH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 202415.3 €

After decades of perfecting the established way of computing, it is now evident that the fundamental logic of today’s computers will prevent them from ever reaching the efficiency of neural networks as found in nature. Neuromorphic hardware promises a leap forward by following the inherent working principles of biological neural networks. In very-large-scale integrated neuromorphic circuits incorporating an immense number of artificial neurons, the even much larger number of synapses poses the challenge of imitating especially the synaptic functionality in a most compact way. Over the last years, various memristive devices have been proposed to represent the weight of a synapse, determining how well electrical spikes are transmitted from one neuron to another. Existing attempts to achieve spike-timing-dependent plasticity, however, possess inherent problems. The NEURAMORPH project aims to develop a simple and compact circuit element to regulate the access to the memristive device for weight modifications. The dynamics of electrical excitability intrinsic to the employed amorphous semiconductors will naturally be able to mimic spike-timing-dependent plasticity. For full control over the properties of these synaptic access elements, a fundamental understanding of the relaxation processes in such amorphous materials is imperative. To this end, amorphization conditions will be systematically varied over a wide-range to create very distinct amorphous states. As a measure for relaxation the temporal evolution of their electrical properties will then be investigated. Based on experimental results for a variety of materials, molecular dynamics simulations will be employed to elucidate the relationship between elemental composition, structural dynamics and changing electrical excitability. Finally, as proof of concept, a prototype of a neuromorphic chip will be developed incorporating the new kind of synaptic device.

Mots-clés : neuromorphic hardware
Projet ERC : NEURAMORPH (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Münster — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WWU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1297052.7 €

After decades of perfecting the established way of computing, it is now evident that the fundamental logic of today’s computers will prevent them from ever reaching the efficiency of neural networks as found in nature. Neuromorphic hardware promises a leap forward by following the inherent working principles of biological neural networks. In very-large-scale integrated neuromorphic circuits incorporating an immense number of artificial neurons, the even much larger number of synapses poses the challenge of imitating especially the synaptic functionality in a most compact way. Over the last years, various memristive devices have been proposed to represent the weight of a synapse, determining how well electrical spikes are transmitted from one neuron to another. Existing attempts to achieve spike-timing-dependent plasticity, however, possess inherent problems. The NEURAMORPH project aims to develop a simple and compact circuit element to regulate the access to the memristive device for weight modifications. The dynamics of electrical excitability intrinsic to the employed amorphous semiconductors will naturally be able to mimic spike-timing-dependent plasticity. For full control over the properties of these synaptic access elements, a fundamental understanding of the relaxation processes in such amorphous materials is imperative. To this end, amorphization conditions will be systematically varied over a wide-range to create very distinct amorphous states. As a measure for relaxation the temporal evolution of their electrical properties will then be investigated. Based on experimental results for a variety of materials, molecular dynamics simulations will be employed to elucidate the relationship between elemental composition, structural dynamics and changing electrical excitability. Finally, as proof of concept, a prototype of a neuromorphic chip will be developed incorporating the new kind of synaptic device.

Mots-clés : neuromorphic hardware