Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ARMOR-T (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1636710.0 €

Adoptive T cell therapy (ACT) is a powerful approach to treat even advanced cancer diseases where poor prognosis calls for innovative treatments. However ACT is critically limited by insufficient T cell infiltration into the tumor, T cell activation at the tumor site and local T cell suppression. Few advances have been made in the field to tackle these limitations besides increasing T cell activation. My group has focussed on these unaddressed issues but came to realise that tackling these one by one will not be sufficient. I have developed a panel of unpublished chemokine receptors and innovative modular antibody-activated receptors which have the potential to overcome the limitations of ACT against solid tumors. This ground-breaking portfolio places my group in the unique position to address combination of synergistic receptors and enable cellular therapies in previously unsuccessful indications. My project will provide the rationale for provision of an effective cancer treatment. The goal is to develop the next generation of ACT through T cell engineering both by forced expression of migratory and activating receptors and simultaneous deletion of immune suppressive molecules by gene editing. ARMOR-T will provide the basis for further preclinical and clinical development of a pioneering cellular product devoid of the limitations of available products to date. I will prove 1) synergy between migratory and modular activating receptors, 2) feasibility to integrate gene editing into a T cell expansion protocol, 3) synergy between gene editing, migratory and modular receptors and 4) efficacy, safety and mode of action. The main work of the project will be carried out in models of pancreatic cancer. The ARMOR-T platform will subsequently be translated to other cancer entities where response to ACT is likely such as melanoma, breast or colon cancer, providing less toxic and more effective therapies to otherwise untreatable disease.

Mots-clés : adoptive cellular therapy,t cell engeneering,cancer immunotherapy
Projet ERC : CeraText (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Montanuniversität Leoben — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1985000.0 €

Advanced ceramics are often combined with metals, polymers or other ceramics to produce structural and functional systems with exceptional properties. Examples are resistors and capacitors in microelectronics, piezo-ceramic actuators in car injection devices, and bio-implants for hip joint replacements. However, a critical issue affecting the functionality, lifetime and reliability of such systems is the initiation and uncontrolled propagation of cracks in the brittle ceramic parts, yielding in some cases rejection rates up to 70% of components production. The remarkable “damage tolerance” found in natural materials such as wood, bone or mollusc, has yet to be achieved in technical ceramics, where incipient damage is synonymous with catastrophic failure. Novel “multilayer designs” combining microstructure and architecture could change this situation. Recent work of the PI has shown that tuning the location of “protective” layers within a 3D multilayer ceramic can increase its fracture resistance by five times (from ~3.5 to ~17 MPa∙m1/2) relative to constituent bulk ceramic layers, while retaining high strength (~500 MPa). By orienting the grain structure, similar to the textured and organized microstructure found in natural systems such as nacre, the PI has shown that crack propagation can be controlled within the textured ceramic layer. Thus, I believe tailored microstructures with controlled grain boundaries engineered in a layer-by-layer 3D architectural design hold the key to a new generation of “damage tolerant” ceramics. This proposal outlines a research program to establish new scientific principles for the fabrication of innovative ceramic components that exhibit unprecedented damage tolerance. The successful implementation of microstructural features (e.g. texture degree, tailored internal stresses, second phases, interfaces) in a layer-by-layer architecture will provide outstanding lifetime and reliability in both structural and functional ceramic devices.

Mots-clés : bio inspired materials,architectural design,damage tolerance,fracture mechanics,mechanical testing
Projet ERC : FIBCAN (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 2125000.0 €

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 : MOSAIC (Horizon 2020, appel 2017, Consolidator 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 : 1997060.0 €

Advances in DNA sequencing technology, enabling routine genetic variation studies, have uncovered that genomic structural variants (SVs; e.g. deletions and inversions) account for most varying bases in human genomes. SVs are also disproportionally associated with disease phenotypes when compared to single nucleotide variants by number. Studies are increasingly implicating genetic polymorphisms with diseases – yet why some humans develop diseases while others do not, and why disease incidences often increase with age, is largely unclear. Intriguingly, recent studies showed that human genetic variation extends markedly beyond heritable variants. Soon after fertilization, mutations naturally accumulate in healthy tissues resulting in somatic genetic mosaicism (SGM), a highly understudied form of variation. Among SGM classes, ‘SV mosaicisms’ likely account for most varying bases, are increased at age, are seen in the context of clonal cell expansion, and are associated with diseases of the elderly including type 2 diabetes and cancer. This indicates that to understand the basis of particular diseases we may first need to comprehend how naturally formed somatic SVs impact human cells. Here we aim to uncover the extent and impact of SV mosaicism. We aim to pursue single cell analyses, which offer the most direct way to detect somatic SVs in individual cells. Performing SV analysis in single cells at scale, however, is not a mainstream approach: current methods identify copy-number variants (CNVs), but miss key copy-neutral SV classes (e.g. inversions) likely to be highly relevant. We aim to develop new experimental and computational tools to construct a single cell catalog of a wide variety of relevant SV classes in different cell types (i.e. the blood compartment and skin) and ages. Using this catalog, we aim to study the functional impact of SV mosaicism on the cellular level, as a foundation for elucidating roles of somatic SVs in age-related phenotypes and diseases.

Mots-clés : genomic structural variation,somatic genetic mosaicism
Projet ERC : PEQEM (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497890.0 €

Advances in measurement always lead to dramatic advances in science and in technology. Our society is now heavily dependent on the sensors that permeate environmental monitoring, security, healthcare and commerce. This is quantified by the global sensing market worth rising from $110 billion in 2015 to $124 billion in 2016, and is predicted to continue to rise to $240 billion by 2022. Now, our rapidly growing understanding of how to control quantum systems vastly expands both the potential performance and application for measurement and sensing using quantum-enhanced techniques. But these techniques will only efficiently find disruptive use once they are engineered for robustness, deliver desired operational parameters and are shown to work in a platform that can be mass-produced. This project adopts an engineering approach to the disciplines of photonic quantum enhanced sensing and squeezed light quantum optics. We will develop integrated photonics that are tailored to enable miniature, deployable and ultimately low cost sensors that exceed the state of the art through (i) exploitation of the quantum mechanics of light and by (ii) developing the requisite high performance of components in an integrated photonics platform. The methodology is to combine quantum optics of Kerr-nonlinear materials that generate squeezed light and quantum state detection with photonic device engineering. We will benchmark device performance using quantum metrology techniques. By the end of this project, we will have developed all-integrated squeezed light generation and detection technology, that provides enhanced sensors for absorption and phase measurements beyond the shot noise limit --- the hard limit that bounds performance of state of the art “classical” sensors. Applications include next generation quantum metrology experiments, measurement of photo-sensitive samples, precise characterization of photonic components and trace gas detection.

Mots-clés : silicon photonics,quantum metrology,sub shot noise measurement
Projet ERC : SCARABEE (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Oslo — Pays : Norvège — Rôle : PI
Acronyme de l'entité : UiO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499961.0 €

Advances in sequencing technologies are currently providing an unprecedented opportunity to a detailed discovery of the mechanisms involved in the evolution and spread of microbes causing human infectious disease. Simultaneously the developers of statistical methods face an enormous challenge to cope with the wealth of data brought by this opportunity. We have very recently demonstrated the ability of our advanced computational approaches to deliver breakthroughs in understanding pathogen evolution and transmission in numerous highlight results published in Science, PNAS and top-ranking Nature journals. The rise of microbial Big Data gives a promise of a giant leap in making causal discoveries, however, the existing statistical methods are neither able to cope with the size and complexity of the emerging data sets nor designed to answer the novel biological questions they enable. To fulfil the promise of giant leaps SCARABEE will leverage scalable inference methods by a unique combination of machine learning algorithms and Bayesian statistical models for evolutionary epidemiology. We focus on central biological questions about adaptation, epistasis, genome evolution and transmission of microbes causing infectious disease. The Big Data combined with the novel inference methods will make it possible to answer a multitude of important questions that remain currently intractable. Through our close collaboration with the leading research centres in infectious disease epidemiology and genomics we expect the SCARABEE project to considerably advance understanding of the evolution and transmission of numerous pathogens that pose a major threat to human health, which will be important for reducing their disease burden in the future. Large-scale biological data will be used to benchmark the developed methods, which will be made publicly available as free software packages to benefit the wide community of microbiologists and infectious disease epidemiologists.
Projet ERC : SynOxyS (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999995.0 €

Aerobic organisms developed systems to measure cellular oxygen levels and activAerobic organisms developed systems to measure cellular oxygen levels and activate adaptive responses in case hypoxia occurs. This condition can be caused by sudden environmental changes or associated with developmental programmes. Recent reports have revealed that complex eukaryotes, such as plants and animals, converged towards the recruitment of dioxygenase enzymes to regulate gene targets at the transcriptional level. However, while the sensing strategy is the same, the molecular identity of the components involved is different. The similarities and differences between animal and plant hypoxia machineries can be exploited to acquire better understanding of the dynamics of oxygen sensing in the two kingdoms and more precise manipulation of these mechanisms for farming proposes. Here, I plan to apply a novel approach that merges the synthetic biology framework, molecular physiology and developmental biology to transfer features of the metazoan oxygen sensing and delivery systems to plants. This strategy will be instrumental to investigate for the first time whole oxygen machineries and characterize their performance in the context of plant cells. More specifically, the proposed project expands in three distinct although interlinked directions that explore (1) the exploitation of 2-OG dioxygenase to drive selective proteolysis in higher plants, (2) the investigation of endogenous or heterologous control of chromatin accessibility by 2-OG dioxygenases and (3) the engineering of a synthetic delivery delivery system to alter oxygen provision or perception specifically to shoot apical meristems. The process of design and optimization of these synthetic oxygen machineries, and the comparison with endogenous ones, will allow pinpointing the features that enable efficient control of hypoxic responses and specifically controlling adaptive responses that ameliorate hypoxia tolerance in plants.

Mots-clés : oxygen,hypoxia,selective proteolysis,synthetic biology,oxygen delivery,flooding,camelina sativa,arabidopsis thaliana,shoot meristem development
Projet ERC : A-LIFE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Vienna — Pays : Autriche — Rôle : PI
Acronyme de l'entité : Univie
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1987980.0 €

Aerosols (i.e. tiny particles suspended in the air) are regularly transported in huge amounts over long distances impacting air quality, health, weather and climate thousands of kilometers downwind of the source. Aerosols affect the atmospheric radiation budget through scattering and absorption of solar radiation and through their role as cloud/ice nuclei. In particular, light absorption by aerosol particles such as mineral dust and black carbon (BC; thought to be the second strongest contribution to current global warming after CO2) is of fundamental importance from a climate perspective because the presence of absorbing particles (1) contributes to solar radiative forcing, (2) heats absorbing aerosol layers, (3) can evaporate clouds and (4) change atmospheric dynamics. Considering this prominent role of aerosols, vertically-resolved in-situ data on absorbing aerosols are surprisingly scarce and aerosol-dynamic interactions are poorly understood in general. This is, as recognized in the last IPCC report, a serious barrier for taking the accuracy of climate models and predictions to the next level. To overcome this barrier, I propose to investigate aging, lifetime and dynamics of absorbing aerosol layers with a holistic end-to-end approach including laboratory studies, airborne field experiments and numerical model simulations. Building on the internationally recognized results of my aerosol research group and my long-term experience with airborne aerosol measurements, the time seems ripe to systematically bridge the gap between in-situ measurements of aerosol microphysical and optical properties and the assessment of dynamical interactions of absorbing particles with aerosol layer lifetime through model simulations. The outcomes of this project will provide fundamental new understanding of absorbing aerosol layers in the climate system and important information for addressing the benefits of BC emission controls for mitigating climate change.

Mots-clés : climate change,air quality,absorbing aerosol,aerosol long range transport,mixing and aging,aerosol dynamic interaction,aircraft observations,remote sensing,radiative transfer,atmosph  models
Projet ERC : CMBforward (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : Cardiff University — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1915814.0 €

After almost two decades, the Standard Model of cosmology remains deeply unsatisfactory and incomplete from a theoretical viewpoint. Cosmic Microwave Background (CMB) observations provide a unique window into the early universe and are key to answering our most important and unresolved questions. The CMB has been mapped recently with unprecedented precision by the Planck satellite. However, its full potential in testing fundamental physics lies in measurements of its polarization at high resolution and sensitivity. This will be unlocked for the first time with current and future ground-based experiments. The Atacama Cosmology Telescope (ACT) is one of the leading experiments currently operating and from 2021 the new Simons Observatory (SO) will supersede all existing and funded instruments. CMBforward is a programme capitalizing on my expertise built with Planck and ACT, to deliver new CMB cosmology from ACT (during 2020-22) and SO (from 2022) that will advance the state of the art. I will lead work that will take great strides in constraining the properties of neutrinos, the nature of the primordial fluctuations seeding the cosmic structures, the physics of dark matter and dark energy, and the time of cosmic dawn. Recognizing the need and importance of a new dedicated CMB satellite, I will also lead, working closely with other European partners and space agencies, the design of the next CMB mission with European contribution. This proposal presents a workplan for the development of new, more precise, and robust data analysis techniques, and requests support for the research time and resources needed for analysis and scientific exploitation of the high volume of incoming data. Building on my expertise in characterizing and interpreting CMB data, and with leadership established and secured in key current and future experiments, this project is unique in bringing together past, present and future CMB studies, and will be at the forefront of key frontiers in cosmology.

Mots-clés : neutrino physics,inflationary cosmologies
Projet ERC : QU-BOSS (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : International Iberian Nanotechnology Laboratory — Pays : Portugal — Rôle : Partner
Acronyme de l'entité : INL
Type d'entité : Recherche
Financement ERC de l'entité : 190000.0 €

After decades of progress in quantum information science, it is widely expected that in the next few years the field will start to yield practical applications in quantum chemistry, materials and pharmaceutical research, information security, and finance. For these applications to pan out, a crucial intermediate goal is to reach the quantum advantage regime, where quantum devices experimentally outperform classical computers in some computational task. The Boson Sampling problem is an example of a task that is computationally hard for classical computers, but which can be solved with a specialized quantum device using single photons interfering in a multimode linear interferometer. The aim of QU-BOSS is to experimentally push towards the quantum advantage regime with integrated photonic technology. The key innovative ingredient is the introduction of non-linearities acting at the single photon level embedded within the Boson Sampling interferometer. We plan to provide an experimental research breakthrough along three main directions, including both “hardware” and “software” components. First, we will use complementary approaches to map out how the addition of non-linearity boosts the device ́s complexity, making it harder to simulate classically. We will use different approaches to implement these devices with hybrid integrated quantum photonics, a versatile and flexible route to the manipulation of high-dimensional quantum photonic states. Finally, we will deploy the developed technology to implement two different architectures demonstrating quantum machine learning: a hybrid model of quantum computation and an optical quantum neural network. QU- BOSS aims to position integrated photonics into the NISQ (noisy, intermediate-scale quantum) era, opening up truly new scientific horizons at the frontier of quantum information, quantum control, machine learning and integrated photonics.

Mots-clés : integrated quantum photonics,single photon sources,reconfigurable circuits,boson sampling,quantum machine learning,quantum networks,machine learning enhanced quantum information