Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : WIDE (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2496875.0 €

Although homo sapiens has been endowed with language for over 50,000 years, the invention of alphabet-like scripts 3,000 years ago dominates Western linguistic thinking. Training in literacy starts in early childhood, and because of this, words and letter-like sound units can naturally seem to be the building blocks of language. The Chinese writing system highlights the cultural-specificity of this approach: characters are juxtaposed without intervening spaces, and their interpretation is highly context-dependent. Words are not singled out. And although more frequent characters contain parts indicating pronunciation, it is syllables that are referred to, not letter-like sound units. The research proposed here seeks to break the hold that the alphabet-centric approach has on our understanding of language by exploring the idea that instead of being phone and word-based, languages use low-level properties of the acoustic signal to directly reduce uncertainty about the messages encoded in the speech signal. My work with wide learning networks (two-layer networks with many thousands of units, using the simplest possible error-driven learning rule) provides remarkable support for this suggestion: For reading and speech comprehension, their performance closely matches both the strengths and the weaknesses of human processing. Especially at a time when machine learning and artificial intelligence are moving beyond human capacity, it is a methodological imperative to study and work with algorithms reflecting both the advantages and disadvantages of human learning. I am requesting funding to take this radically novel research program to the next level by further developing our account of auditory comprehension, by modeling more typologically diverse languages, by extending this approach to speech production, and by developing a discrimination-based language theory.

Mots-clés : wide learning,speech comprehension,speech production,computational modeling,naive discrimination learning
Projet ERC : MYMOVE (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : Vrije Universiteit Brussel — Pays : Belgique — Rôle : Partner
Acronyme de l'entité : VUB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 112500.0 €

Although many immigrant children are more likely to move within the country of settlement than native born youth, little is known on the potential effects of this so called internal mobility. When does childhood internal mobility have negative consequences on an individual’s life? Are there differences in processes and consequences for those of immigrant and non-immigrant background? Do the number of moves or the reason for moving make a difference? Is the age at which moving takes place decisive and is distance relevant? Despite the fact that moving is a major stress-inducing life event, so far little is known on the potential consequences of childhood internal mobility for people of diverse immigrant origins. Given Europe’s diverse population and immigration being the key factor in population change, it is crucial to understand if, how and for whom childhood internal mobility matters. The main objective of the MYMOVE project is to advance knowledge on the relationship between childhood internal mobility and adult life chances as defined by demographic family life choices, health and well-being for those with and without immigrant background. The project makes five innovative contributions to the so far scattered literature. It will 1) comprehensively map childhood internal mobility patterns; 2) study its mid- and long-term consequences for diverse immigrant groups and the native-born; 3) cover two key outcomes that are crucial in the individual life path (demographic family behaviour and health and well-being); 4) simultaneously study different dimensions of internal mobility (number, reason, timing, distance), and 5), distinguish three levels of influence that may moderate the effect of internal mobility (the neighbourhood of origin and destination, family background, and individual characteristics). The MYMOVE project will break new ground by using unique and new longitudinal (full-) population register and survey panel data from across Europe.

Mots-clés : immigrants,internal mobility,later life outcomes,life course,demography
Projet ERC : Multiscreen (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : École polytechnique — Pays : France — Rôle : Partner
Acronyme de l'entité : X
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 10310.0 €

Although some biotechnologies have made huge strides e.g. in automation, data generation, or biochemical methods, cell handling still uses antiquated methods that limit the scale at which assays can be performed. Our ERC-funded microfluidics work has lead to cutting-edge microdroplet manipulation tools for cell handling: While working with 3D cell cultures, we have recently shown that we can obtain great increases in both throughput and detail, while reducing the sample use and the machine footprint. In addition to these quantitative leaps, the microfluidic format also allows qualitatively new biological constructs to be explored by making significant steps towards the organ-on-a-chip framework. The current project therefore aims to show how the technologies developed in our lab can function together in an integrated cell screening platform. This will require demonstrating a convincing proof of concept of the hardware, software, and workflow, in addition to demonstrating the added value to different industries.

Mots-clés : microfluidics,drug screening,bio engineering,3d cell culture
Projet ERC : MOBILISE (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Although the number of anti-inflammatory drugs has increased during the past decade, there is still an urgent need to develop novel alternatives that overcome limitations of current treatments. The most used therapies, such as non-steroidal anti-inflammatory drugs, non-analgesic anti-inflammatory drugs or colchicine, often present severe side-effects. In addition, in recent years biologicals have appeared, but they are extremely expensive. Therefore, novel therapeutic approaches with lower toxicity, higher tolerance and lower price must be developed to treat autoinflammatory and autoimmune diseases. Since the NLRP3 inflammasome is a key contributor of inflammatory diseases (including gout, pseudogout, metabolic arthropathies and multiple sclerosis), its targeting has become very relevant for the development of novel therapeutics. As part of our ERC project STePS, we discovered a novel activation pathway to the NLRP3 inflammasome, which opens new opportunities to use an existing line of compounds for radically new medical indications. Within STePS, we uncovered the activation of the NLRP3 inflammasome by the enzyme Monoamine Oxidase B (MAO-B) through ROS production, positioning MAO-B as a promising target to treat autoinflammatory and autoimmune diseases. Given that there are several MAO-B inhibitors (iMAO-B) currently used in the clinic for treatment against Parkinson disease, the use of iMAO-B represent a major opportunity to develop new therapies at low risk and a fraction of the cost. This ERC PoC MOBILISE will assess the technical and commercial feasibility of repositioning iMAO-B as a novel treatment of gout and other NLRP3 inflammasome-driven diseases. Within MOBILISE, we aim to explore the efficacy in vivo of iMAO-B, solidify our IP protection, perform an extensive market and competitor analysis and develop a detail business plan to define the optimal commercialisation route for MAO-B inhibitors in gout and other autoinflammatory diseases.

Mots-clés : monoamine oxidase inhibitors,nlrp3 inflammasome,autoimmune diseases,autoinflammatory diseases,gout
Projet ERC : SYNVIA (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Bern — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999437.5 €

Although various effective anti-cancer drug treatments have become available over the last decades, drug resistance remains the major cause of death of cancer patients. Striking examples are patients with tumors that are defective in DNA repair by homologous recombination (HR). Despite initial responses to cancer therapy, resistance of primary or disseminated tumors eventually emerges, which minimizes therapeutic options and greatly reduces survival. The molecular mechanisms underlying this therapy escape are often poorly understood. In the SYNVIA project I will address the problem of therapy escape by using powerful genetically engineered mouse models for BRCA1- and BRCA2-deficient breast cancer, which closely mimic the human disease. Due to the BRCA inactivation, the tumors that arise lack HR-directed DNA repair. Similar to the situation in cancer patients, we observe that cancer cells in these models eventually escape the deadly effects of chemotherapy or novel targeted drugs. Thus, these resistance models provide a unique opportunity to explore therapy escape mechanisms. I propose an approach that will take the in vivo analysis of therapy resistance mechanisms to a new level. By synergizing the advantages of next generation sequencing with functional genetic screens in tractable model systems, I will explore novel mechanisms that cause resistance of HR-deficient cancers by the loss of another gene (“synthetic viability”). I provide evidence that new mechanisms of resistance can be identified with this approach. In an innovative step, I will generate genome-wide alterations using the revolutionizing CRISPR/Cas technology. Mutations will also be introduced into 3D tumor organoid cultures, as we found that these are more physiologically relevant. I am convinced that the combination of these state-of-the-art approaches will yield highly useful information for designing effective approaches to circumvent or reverse therapy escape in human cancer patients.

Mots-clés : brca1,breast cancer,anti cancer drug resistance,dna repair,crispr,genomic screens,3d organoid cultures
Projet ERC : AAA (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Commissariat à l’énergie atomique et aux énergies alternatives — Pays : France — Rôle : Partner
Acronyme de l'entité : CEA
Type d'entité : Recherche
Financement ERC de l'entité : 1173995.5 €

Although we have extensive knowledge of many important processes in cell biology, including information on many of the molecules involved and the physical interactions among them, we still do not understand most of the dynamical features that are the essence of living systems. This is particularly true for the actin cytoskeleton, a major component of the internal architecture of eukaryotic cells. In living cells, actin networks constantly assemble and disassemble filaments while maintaining an apparent stable structure, suggesting a perfect balance between the two processes. Such behaviors are called “dynamic steady states”. They confer upon actin networks a high degree of plasticity allowing them to adapt in response to external changes and enable cells to adjust to their environments. Despite their fundamental importance in the regulation of cell physiology, the basic mechanisms that control the coordinated dynamics of co-existing actin networks are poorly understood. In the AAA project, first, we will characterize the parameters that allow the coupling among co-existing actin networks at steady state. In vitro reconstituted systems will be used to control the actin nucleation patterns, the closed volume of the reaction chamber and the physical interaction of the networks. We hope to unravel the mechanism allowing the global coherence of a dynamic actin cytoskeleton. Second, we will use our unique capacity to perform dynamic micropatterning, to add or remove actin nucleation sites in real time, in order to investigate the ability of dynamic networks to adapt to changes and the role of coupled network dynamics in this emergent property. In this part, in vitro experiments will be complemented by the analysis of actin network remodeling in living cells. In the end, our project will provide a comprehensive understanding of how the adaptive response of the cytoskeleton derives from the complex interplay between its biochemical, structural and mechanical properties.
Projet ERC : aLzINK (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
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 : 69356.25 €

Alzheimer's disease (AD) is one of the most serious diseases mankind is now facing as its social and economical impacts are increasing fastly. AD is very complex and the amyloid-β (Aβ) peptide as well as metallic ions (mainly copper and zinc) have been linked to its aetiology. While the deleterious impact of Cu is widely acknowledged, intervention of Zn is certain but still needs to be figured out. The main objective of the present proposal, which is strongly anchored in the bio-inorganic chemistry field at interface with spectroscopy and biochemistry, is to design, synthesize and study new drug candidates (ligands L) capable of (i) targeting Cu(II) bound to Aβ within the synaptic cleft, where Zn is co-localized and ultimately to develop Zn-driven Cu(II) removal from Aβ and (ii) disrupting the aberrant Cu(II)-Aβ interactions involved in ROS production and Aβ aggregation, two deleterious events in AD. The drug candidates will thus have high Cu(II) over Zn selectively to preserve the crucial physiological role of Zn in the neurotransmission process. Zn is always underestimated (if not completely neglected) in current therapeutic approaches targeting Cu(II) despite the known interference of Zn with Cu(II) binding. To reach this objective, it is absolutely necessary to first understand the metal ions trafficking issues in presence of Aβ alone at a molecular level (i.e. without the drug candidates).This includes: (i) determination of Zn binding site to Aβ, impact on Aβ aggregation and cell toxicity, (ii) determination of the mutual influence of Zn and Cu to their coordination to Aβ, impact on Aβ aggregation, ROS production and cell toxicity. Methods used will span from organic synthesis to studies of neuronal model cells, with a major contribution of a wide panel of spectroscopic techniques including NMR, EPR, mass spectrometry, fluorescence, UV-Vis, circular-dichroism, X-ray absorption spectroscopy...

Mots-clés : bio inorganic chemistry,peptides,copper,zinc,aggregation,ligands
Projet ERC : aLzINK (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
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 : 1372760.0 €

Alzheimer's disease (AD) is one of the most serious diseases mankind is now facing as its social and economical impacts are increasing fastly. AD is very complex and the amyloid-β (Aβ) peptide as well as metallic ions (mainly copper and zinc) have been linked to its aetiology. While the deleterious impact of Cu is widely acknowledged, intervention of Zn is certain but still needs to be figured out. The main objective of the present proposal, which is strongly anchored in the bio-inorganic chemistry field at interface with spectroscopy and biochemistry, is to design, synthesize and study new drug candidates (ligands L) capable of (i) targeting Cu(II) bound to Aβ within the synaptic cleft, where Zn is co-localized and ultimately to develop Zn-driven Cu(II) removal from Aβ and (ii) disrupting the aberrant Cu(II)-Aβ interactions involved in ROS production and Aβ aggregation, two deleterious events in AD. The drug candidates will thus have high Cu(II) over Zn selectively to preserve the crucial physiological role of Zn in the neurotransmission process. Zn is always underestimated (if not completely neglected) in current therapeutic approaches targeting Cu(II) despite the known interference of Zn with Cu(II) binding. To reach this objective, it is absolutely necessary to first understand the metal ions trafficking issues in presence of Aβ alone at a molecular level (i.e. without the drug candidates).This includes: (i) determination of Zn binding site to Aβ, impact on Aβ aggregation and cell toxicity, (ii) determination of the mutual influence of Zn and Cu to their coordination to Aβ, impact on Aβ aggregation, ROS production and cell toxicity. Methods used will span from organic synthesis to studies of neuronal model cells, with a major contribution of a wide panel of spectroscopic techniques including NMR, EPR, mass spectrometry, fluorescence, UV-Vis, circular-dichroism, X-ray absorption spectroscopy...

Mots-clés : bio inorganic chemistry,peptides,copper,zinc,aggregation,ligands
Projet ERC : AD_AGING_AND_GENDER (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1500000.0 €

AlzheimerAlzheimer’s disease (AD) is a crucial problem in our society, raising the need for new therapeutic targets. Evidence suggests multiple non-neuronal cells are implicated in the systemic deficits of AD, but the complex cellular diversity in the brain hampers the investigation of specific cells and their interactions. Moreover, the course of the disease is highly variable, due to multiple risk factors, including aging and gender, which have overlapping molecular signatures with AD that might be further masking disease mechanisms. I propose to expand the resolution from tissues to cellular environments, and to untangle overlapping molecular signatures of gender and aging, in order to unmask molecular mechanism of AD. Technological advances in genomics and imaging, including the single nucleus RNA-sequencing methods developed by me, as well as my expertise in computational analysis and CRIPSR perturbations, provide a unique opportunity to address this challenge. I obtained preliminary results strongly suggesting that multiple cell types are indeed altered in AD brains of mice and humans, and that gender, aging, and AD have overlapping molecular features. I hypothesize that age-dependent cellular/molecular alterations are key drivers of cognitive decline, and that the dynamics of these alterations determine risk and resilience levels in individuals. We will test this hypothesis by: 1) Charting the cellular microenvironments and tissue topology of the human AD brain, to reveal cells, pathways, and cellular interactions driving AD; 2) Mapping the dynamic cellular/molecular trajectories in aging and AD in w.t. and AD mice, to untangle AD, aging, and gender dimorphism; and 3) Identifying regulators of cognitive resilience and decline in AD and aging, and connecting genes to function by detailed mechanistic investigations in vivo. Overall, our innovative proposal is expected to advance our understanding of AD mechanism, and the link to aging and gender dimorphism.
Projet ERC : STEMAD3D (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1666957.0 €

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease. Despite the significant progress made towards unpacking the pathomechanisms of AD, the molecular and cellular mechanisms underlying AD pathogenesis remain poorly understood. Previous studies mainly relied on animal models that do not capture human-specific biology, monolayer neural cultures that do not capture pathological hallmarks of the disease, and post-mortem tissues that only capture disease end-stage. There is thus a pressing need for new complementary approaches that preserve the disease genetics, mimic disease pathology, and more closely reflect human brain environment. I have developed a chimeric system for transplantation of Induced Pluripotent Stem Cells (iPSC)-derived brain organoids into the mouse brain, providing a powerful platform to study AD under a physiological environment. This project aims to understand the molecular and cellular aberrations underlying AD pathogenesis. I propose to achieve this goal via a novel combination of a chimeric model, iPSC-based patient-specific brain organoids, transcriptomics, epigenetics, and genetic editing approaches. We will determine the disease-associated progressive changes at the transcriptome level, examine the cellular aberrations both in vitro and within the in vivo brain environment, and identify molecular regulators that underlie disease deficits and might enhance susceptibility to AD manifestation. Next, we will define perturbations in the epigenetic landscape associated with AD. Finally, this project seeks to extend towards identifying critical mechanisms that govern the interplay between neurons and the immune system in AD. I anticipate that this research will uncover novel molecular, cellular, and functional mechanisms that govern AD pathology, and may provide a basis for developing future therapeutic strategies.

Mots-clés : stem cells,alzheimer s disease,induced pluripotent stem cells,organoids,animal chimera