Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PhenoSwitch (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Technion – Israel Institute of Technology — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1906250.0 €

The limited success of cancer therapy especially in advanced metastatic disease warrants a reassessment, especially given our limited understanding of the nature of cancer cells and the factors that allow them to proliferate and metastasise. Stromal cells of the tumour microenvironment, including fibroblasts, endothelial, immune, adipose and mesenchymal cells, significantly affect cancer cell characteristics and tumour fate; however, their sometimes dichotomous function in high- and low-aggressive tumours has not been thoroughly investigated. Here, we propose to elucidate the largely unknown role of haematopoietic stem and/or progenitor cells (HSCs) on tumour growth and metastases. We found that such cells reside in the tumour niche predominantly in non-aggressive tumours. We hypothesise that cancer cells trigger the differentiation of HSCs into haematopoietic tumour-supporting stromal cells, thereby inducing a phenotypic and functional switch that skews them towards a tumour-promoting phenotype, hence promoting tumour cell aggressiveness and metastases. To test our hypothesis, we will use high-throughput technologies to track the lineage, differentiation and commitment of HSCs during tumour progression. Our specific aims are therefore: (a) To systematically analyse tumour-promoting and tumour-restricting stromal phenotypes at the cellular and molecular levels. (b) To characterise stromal cell plasticity and the contribution of tumour cells to the phenotype switch. (c) To determine whether differentiated stromal cells and HSCs in cancer patients can predict clinical outcome. (d) To screen for molecules that inhibit the tumour-promoting stromal switch. Blocking the tumour-promoting phenotypic switch and maintaining a pre-mature tumour-restricting stromal microenvironment represent a novel strategy in the fight against cancer. This study will lead to the development of new tools to predict prognosis and pharmacological strategies to restrict tumour growth.

Mots-clés : haematopoietic stem cells,tumor microenvironment,macrophages,myeloid cells,angiogenesis,treatment modalities for cancer,metastasis,biomarkers
Projet ERC : CircaCHIP (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Hebrew University of Jerusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149969.0 €

The liver is responsible for the systemic regulation of human metabolism, responding to a dynamically changing hormonal and nutritional environment. These physiological dynamics limited our ability to model human metabolism in our efforts to create efficient pharmaceutical interventions for prevalent metabolic diseases, such as fatty liver disease, obesity, and type-2 diabetes. In addition, physiological dynamics impact the pharmacokinetics and toxicity of drugs due to circadian changes in drug metabolism, affecting our ability to formulate efficient pharmaceutical interventions or properly assess drug toxicity (i.e. Chronopharmacology). The problem stems from our inability to model the dynamics of human metabolism in vitro, and compounded by the failure of animal models to predict human response due to differences in physiology, metabolic regulation, and an inverted day/night cycles. In addition, in vitro hepatocytes show little to no metabolic function and lack the physiological complexity of human tissue. Therefore, there is a pressing need to develop models that mimic human physiological complexity. Recently, we established groundbreaking libraries of expandable human hepatocytes (Levy et al. Nature Biotechnology 2015) and a cutting-edge liver-on-chip platform that tracks metabolic dynamics in real time (Bavli et al. PNAS 2016). Our technology explained the idiopathic toxicity of acetaminophen and the idiosyncratic toxicity of troglitazone and was recently highlighted by the H2020 program. Here, we describe the development of a novel platform that captures the synchronization of circadian rhythms in self-assembled human micro-livers by microfluidic oscillations of temperature and hormones. Our next generation model for liver metabolism will present a quantum leap in capability, offering to go beyond animal models by predicting time-of-day dependent toxicity and drug clearance. In addition, we will enable the rational design of a new generation of pharmaceuticals

Mots-clés : in vitro toxicology,microfluidics,human on chip,liver biology,drug metabolism
Projet ERC : OCLD (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Hebrew University of Jerusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2118175.0 €

The liver is the main organ responsible for the systemic regulation of human metabolism, responding to hormonal stimulation, nutritional challenges, and circadian rhythms using fast enzymatic processes and slow transcriptional mechanisms. This regulatory complexity limits our ability to create efficient pharmaceutical interventions for metabolic diseases such as fatty liver disease and diabetes. In addition, circadian changes in drug metabolism can impact pharmacokinetics and pharmacodynamics affecting our ability to optimize drug dosage or properly assess chronic liver toxicity. The challenge in rationally designing efficient drug interventions stems from current reliance on end-point assays and animal models that provide intermittent information with limited human relevance. Therefore, there is a need to develop systems capable of tracking transcriptional and metabolic dynamics of human tissue with high-resolution preferably in real time. Over the past 5 years, we established state-of-the-art models of human hepatocytes; oxygen nanosensors; and cutting-edge liver-on-chip devices, making us uniquely suited to address this challenge. We aim to develop a platform capable of tracking the metabolism of tissue engineered livers in real time, enabling an accurate assessment of chronic liver toxicity (e.g. repeated dose response) and the deconstruction of complex metabolic regulation during nutritional events. Our approach is to integrate liver-on-chip devices, with real time measurements of oxygen uptake, infrared microspectroscopy, and continuous MS/MS analysis. This innovative endeavour capitalizes on advances in nanotechnology and chemical characterization offering the ability to non-invasively monitor the metabolic state of the cells (e.g. steatosis) while tracking minute changes in metabolic pathways. This project has the short-term potential to replace animal models in toxicity studies and long-term potential to elucidate critical aspects in metabolic homeostasis.

Mots-clés : biomems,human on chip,bioreactors,liver metabolism,circadian rhythms,chrono pharmacology,predictive toxicology,sensors
Projet ERC : TheTocharianTrek (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499980.0 €

The long trek of the Tocharians from Europe to China is one of the most disputed issues in the migration history of Eurasia. Tocharian is an extinct branch of the Indo-European language family, which includes a.o. English, Latin, Greek and Sanskrit. The Indo-European languages stretch in one uninterrupted belt from Ireland to the Sea of Bengal, but Tocharian, discovered in manuscripts from the Tarim Basin in Northwest China dating from c. 500–1000 CE, is a notorious exception to this geographic distribution. The common ancestor of the Indo-European languages, Proto-Indo-European, can be hypothetically reconstructed and is often located in the east of present-day Ukraine. Therefore, speakers of early Tocharian must have made a long trek eastward before they settled in the Tarim Basin. Archaeological and genetic evidence suggests that they first moved east to southern Siberia around 3500 BCE and then south to the Tarim Basin in China, where they may have arrived as early as 2000 BCE. The arrival of the Tocharians in the Tarim Basin is possibly linked to ancient corpses found there: the so-called Tarim Mummies. Curiously, linguistic evidence has mostly been neglected. Therefore, the proposed project aims to provide an integrated linguistic assessment of the hypothesised migration route of the Tocharians. Languages preserve precious information about their prehistory through the effects of language contact. Through close scrutiny and periodisation of the different layers of contact of Tocharian and its prehistoric neighbours, the project will reconstruct the migration route of the Tocharians from the Proto-Indo-European homeland all the way to China. The crucial Siberian phase of the migration shows the groundbreaking nature of the approach. Genetic evidence points to influence from local Siberian populations on the early Tocharians. Likewise, the Tocharian language shows such heavy impact of local Siberian languages that this may be called the “birth of Tocharian”.

Mots-clés : language contact,indo european linguistics,tocharian,siberia,tarim basin
Projet ERC : ImmunoStem (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Pavia — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPV
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 600000.0 €

The low gene manipulation efficiency of human hematopoietic stem cells (HSC) remains a major hurdle for sustainable and broad clinical application of innovative therapies for a wide range of disorders. Indeed, high vector doses and prolonged ex vivo culture are still required for clinically relevant levels of gene transfer even with the most established lentiviral vector-based delivery platforms. Current and emerging gene transfer and editing technologies expose HSC to components potentially recognized by host antiviral factors and nucleic acid sensors that likely restrict their genetic engineering and contribute to broad individual variability in clinical outcomes observed in recent gene therapy trials. Nevertheless, specific effectors are yet to be identified in HSC. We have recently identified an antiviral factor that potently blocks gene transfer in HSC and have discovered small molecules that efficiently counteract it. This is the first example of how manipulating a single host factor can significantly impact gene transfer efficiencies in HSC but likely represents the mere tip of the iceberg of the plethora of innate sensing mechanisms potentially hampering genetic manipulation of this primitive cell compartment. This proposal aims to identify the antiviral factors and innate sensing pathways that prevent efficient modification of HSC and to mitigate their effects using methods developed through a thorough understanding of their mechanisms of action. My approach builds on the innovative concept that understanding the crosstalk between HSC and viral vectors will instruct us on which immune sensors and effectors to avoid and how, with direct implications for all gene engineering technologies. Successful completion of this project will deliver broadly exportable novel paradigms of innate pathogen recognition that will allow ground-breaking progress in the development of cutting-edge cell and gene therapies and to fight infectious and autoimmune diseases.

Mots-clés : haematopoietic stem and progenitor cells,innate immunity,viral vectors,nucleic acid sensing,genetics
Projet ERC : noRAG-TOR (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1499756.0 €

The mTOR complex 1 (mTORC1) is a master regulator of cell growth and metabolism in response to environmental cues, such as nutrients. Its dysregulation is a common feature of several life-threatening disorders, including cancer and metabolic disease. Therefore, understanding how mTORC1 is regulated is of great importance for both basic and translational research. The availability of Amino Acids (AA) is a prerequisite for cell growth, hence a robust mTORC1 regulator. Previous studies on how AA regulate mTORC1 have mainly focused on the lysosomal Rag GTPases and built a complex protein network that coordinatively senses AA to modify Rag activity. According to the current model, AA sufficiency leads to Rag activation, which in turn recruit mTORC1 to the lysosomal surface, where its direct activator Rheb also resides. Although this machinery is indeed important for acute mTORC1 re-activation upon AA re-addition, my preliminary work suggests that additional, Rag-independent mechanisms also exist and have a predominant role to activate mTORC1 in unchallenged cells or following longer re-activation times. In line with this, Rag knockout cells show persistent steady-state mTORC1 activity and grow similarly to their WT counterparts. In stark contrast to previous approaches, this project aims to elucidate the Rag-independent modes of mTORC1 regulation by AA. To achieve this goal, I will 1) use WT and Rag-mutant cells to study the mechanistic differences of basal mTORC1 activation vs. acute re-activation, and 2) identify novel mTORC1 regulators/interactors in Rag-mutant cells, using biochemical assays, proteomic approaches and functional RNAi screens, to build part of the Rag-independent mTOR regulatory network. Overall, this work will identify new mechanisms and principles of mTORC1 activation and thus expand our view on how AA control mTORC1 activity. In addition, it will provide novel mTORC1 regulators, as putative targets for drug development against mTOR-related diseases.

Mots-clés : cell growth,mtorc1,nutrient sensing,amino acids,rags,ageing,metabolism,cell biology,imaging,small gtpases,protein synthesis,functional genomics,proteomics,protein interactions,organelles
Projet ERC : ISOREE (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
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 : 2200000.0 €

The main geochemical features of the mantles of terrestrial planets and asteroids can be attributed to differentiation events that occurred during or shortly after the formation of the Solar System. Numerous questions remain regarding the Earth’s bulk composition and the most likely scenario for its evolution prior to the last major differentiation event caused by a giant impact leading to the formation of the Moon. The aim of this five-year project is to evaluate the state-of-the-art models of the Earth’s early evolution with the following main objectives: (i) Defining precisely the age of the Moon’s formation, (ii) Refining the giant impact model and the Earth-Moon relationship, (iii) Dating the successive magmatic ocean stages on Earth, and (iv) Constraining the Earth mantle’s composition in terms of rare earth element concentrations. These different questions will be addressed using trace elements, radiogenic isotopic systematics (146Sm-142Nd, 147Sm-143Nd, 138La-138Ce) and stable isotopes. ISOREE is a multi-disciplinary project that combines isotope and trace element geochemistry, experimental geochemistry and spectroscopy. A large number of samples will be analysed, including terrestrial rocks with ages up to 3.8 Ga, chondrites, achondrites and lunar samples. This proposal will provide the tools to tackle a vast topic from various angles, using new methodologies and instrumentation and promoting innovation and creativity in European research. This research program is essential to further constrain the major events that occurred very early on in the Earth’s history, such as the Earth’s cooling, its crustal growth, the surface conditions and development of potential habitats for life.
Projet ERC : GRAPHEALTH (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Institute of Photonic Sciences — Pays : Espagne — Rôle : PI
Acronyme de l'entité : ICFO;ICFO-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

The main goal of GRAPHEALTH is to exploit the inherent properties of hybrid graphene – quantum dot detectors in order to enable constant non-invasive health monitoring through vital parameters. Unlike current bulky systems, our approach enables a flexible, compact and wearable health monitoring system for constant monitoring for consumer health applications and muscle health of athletes during exercise or after injury. The hybrid quantum dot and graphene technology exhibits very high sensitivity and the technology is compatible with flexible electronic manufacturing processes, and also more compact detectors than current commercial devices.

Mots-clés : health monitoring,wearables,graphene,quantum dot,photodetector,flexible
Projet ERC : GTRACK (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Institute of Photonic Sciences — Pays : Espagne — Rôle : PI
Acronyme de l'entité : ICFO;ICFO-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

The main goal of GTRACK is to demonstrate a semi-transparent eye-tracking system that is disposed in the line of sight of the user, for portable applications. To this end, we will use hybrid Quantum Dot – Graphene photodetectors. Eye-tracking existed since the 1800’s, but is expected to appear abundantly in our daily lives with the advent of virtual and augmented reality. In the existing systems, the camera has to be placed sufficiently close to the eye to capture enough IR light at sufficiently high resolution, while not blocking the user’s vision. By placing the camera directly on the lens, all these disadvantages are circumvented. Moreover, larger detectors can increase the sensitivity of the detectors and hence decrease the power consumption of the active illumination, which would allow for portable applications.

Mots-clés : eye tracking,wearables,graphene,quantum dot,photodetector,transparent
Projet ERC : ReadCalibration (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Basque Center on Cognition, Brain and Language — Pays : Espagne — Rôle : PI
Acronyme de l'entité : BCBL
Type d'entité : Recherche
Financement ERC de l'entité : 1875000.0 €

The main goal of this project is to demonstrate that reading acquisition (RA) drastically reshapes our phonemic inventory, and to investigate the time-course and fine-grained properties of this recalibration. The main innovative and ground-breaking aspect of this project is the merging of two research fields, (1) reading acquisition and (2) phonemic recalibration, together with a deep and extensive exploration of the (3) perception-production link, which results in a new research line that pushes the boundaries of our understanding of the complex interactions between auditory and visual language perception and production. We will demonstrate that phonemic representations (PRs) become more stable (less dispersed) during the process of learning to read, and that this recalibration varies according to the grapheme-phoneme conversion rules of the reading system. We will explore such recalibration by means of the first cross-linguistic longitudinal study examining the position and dispersion of PRs, both in perception and production of phonemes and words. Secondly, we will explore how recalibration develops when RA is impaired as is the case in dyslexic children –informing the research field on (4) dyslexia– and when pre-reading PRs are unstable as is the case in deaf children with cochlear implants –informing the research field on (5) deafness. Finally, the research will also be extended to PR recalibration during RA in a second language –informing the research on (6) bilingualism. This proposal provides the first systematic investigation of phonemic recalibration during literacy acquisition, and will provide important insight for pragmatic research and theoretical accounts of language perception and production and phonemic recalibration. This project will also have major implications for the clinical field (theories and remediation of dyslexia and deafness) and for social policies and education (bilingualism, spoken and written language teaching).

Mots-clés : phonemic recalibration,reading acquisition,orthographic consistency,dyslexia,deafness,bilingualism
Projet ERC : ModGravTrial (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : Partner
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 231924.24 €

The main goal of this project is to study the fundamental properties of field theories of space-time, their cosmological consequences and observational signatures. My approach aims to use the next generation of cosmological and astrophysical observations to test the validity of General Relativity on scales where it has not been fully tested yet and its resilience against alternative theories with modifications on cosmological scales. I will first study the implications of the quantum aspects of modified gravity theories beyond the tree level analyses for their viability, consistency and predictability. This will reduce the allowed alternative theories significantly. I will then investigate the physical consequences of these theoretically promising theories for cosmological and astrophysical scenarios. As part of my approach, I will use large galaxy surveys to constrain effects on the dynamics of cosmic structure formation from these modifications of gravity. In addition, I will confront modified theoretical predictions with Planck measurements of the Cosmic Microwave Background, type-Ia supernova data, measurements of the Baryon Acoustic Oscillations and gravitational lensing. Along the way, my group and I will crucially contribute to the development of the necessary analytical and numerical tools to exhaustively analyse such data in the search for modifications of gravity. In addition, the recent detection of gravitational waves by the LIGO team has paved an exciting new avenue for testing gravitational theories. These new observations will put even more stringent constraints on alternative theories. As part of the proposed research, I will also extensively exploit this new observational channel to test the validity of General Relativity and put new effects of modified gravity on trial. In particular, the propagation speed of tensor perturbations in modified gravity theories will be severely restricted by observations of gravitational waves.

Mots-clés : modified gravity