Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SLaMM (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Polytechnic University of Turin — Pays : Italie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 87762.78 €

Central nervous system (CNS) tumors are an important cause of morbidity and mortality worldwide. Among them, glioblastoma multiforme (GBM) is the most aggressive and lethal, characterized by extensive infiltration into the brain parenchyma. Under the standard treatment protocols, GBM patients can expect a median survival of 14.6 months, while less than 5% of patients live longer than 5 years. This poor prognosis is due to several factors, including the highly aggressive and infiltrative nature of GBM, resulting in incomplete resection, and the limited delivery of therapeutics across the blood-brain-barrier (BBB). The present project aims at addressing these therapeutic challenges by proposing a nanotechnology-based approach for the treatment of GBM, focused on the selective uptake of drug-loaded multifunctional magnetic solid lipid nanoparticles (SLNs). An external magnetic guidance will help the SLN accumulation on the cerebral endothelium, where, owing to their lipid nature, they will be allowed to enter the CNS. Here, appropriate surface ligands will drive their internalization inside cancer cells. The chemotherapeutic payload will undergo release, allowing a targeted pharmaceutical treatment that will be combined to hyperthermia upon appropriate radiofrequency application. A synergic attack against GBM will thus be performed, consisting of a chemical attack thanks to the drug, and a physical attack thanks to hyperthermia, that will dramatically enhance the possibilities of therapeutic success. By demonstrating the effectiveness of the platform to cross the BBB and to support tumor regression, a huge impact on human healthcare is envisioned. Moreover, further outcomes of this project are expected by considering the development of nanotechnology-based, multi-functional solutions that can easily be adapted to many other high-impact diseases, in particular at the brain level, where BBB crossing poses a crucial obstacle to many therapeutic approaches.

Mots-clés : smart nanomaterials,drug delivery,drug targeting
Projet ERC : ThymusTolerance (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2220000.0 €

Central tolerance is shaped in the thymus, a primary lymphoid organ, where immature T lymphocytes are “educated” into mature cells, capable of recognizing foreign antigens, while tolerating the body’s own components. This process is driven mainly by two separate lineages of thymic epithelial cells (TECs), the cortical (cTEC) and the medullary (mTEC). While cTECs are critical at the early stages of T cell development, mTECs play a pivotal role in negative selection of self-reactive thymocytes and the generation of Foxp3+ regulatory T (Treg) cells. Crucial to the key role of mTECs in the screening of self-reactive T cell clones, is their unique capacity to promiscuously express and present almost all self-antigens, including thousands of tissue-specific antigen (TSA) genes. Strikingly, the expression of most of this TSA repertoire in mTECs is regulated by a single transcriptional regulator called Aire. Indeed, Aire deficiency in mice and human patients results to multi-organ autoimmunity. Although there has been dramatic progress in our understanding of how thymic epithelial cells shape and govern the establishment of adaptive immunity and of immunological self-tolerance, there are still several outstanding questions with no comprehensive answers. Therefore, in the research proposed herein, we wish to provide more comprehensive answers to these still elusive, but very fundamental questions. Specifically we will aim at: 1.) Delineation of molecular mechanisms controlling TEC development and thymus organogenesis; 2.) Delineation of molecular mechanisms underlying promiscuous gene expression in the thymus; 3.) Identification and characterization of molecular determinants responsible for the breakdown of thymus-dependent self-tolerance. To this end, we will build upon our recently published data, as well as unpublished preliminary data and utilize several state-of-the-art and interdisciplinary approaches, which have become an integral part of our lab’s toolbox.

Mots-clés : aire,thymic epithelial cells,thymus,aps 1,central tolerance,autoimmunity
Projet ERC : Mod-L-T (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Trinity College Dublin — Pays : Irlande — Rôle : PI
Acronyme de l'entité : TCD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1943146.88 €

Chemicals, fuels and energy must be produced from lignocellulosic plant-matter if global economies are to decarbonise. To be successful, these lignocellulose-derived products must compete in technical quality and price with fossil derived products. Thus, we must understand what lignocellulose is, and how its chemical structures react in thermochemical processing technologies, such as pyrolysis. Pyrolysis is a promising method to produce valuable products from lignocellulose and the basic fundamental process of more complex thermochemical technologies, such as catalysis. Mod-L-T deciphers the elementary reaction mechanism and kinetics of lignocellulose pyrolysis. Relative to cellulose, the reaction kinetics of hemicellulose and lignin are less studied, and thus the focus of Mod-L-T. Mod-L-T creates the first detailed, elementary, mass- and energy-conserved chemical reaction model for lignocellulose pyrolysis. A compositional characterisation and modelling procedure utilising Nuclear Magnetic Resonance spectroscopy identifies what molecular structures comprise, and best represent actual lignocelluloses. The mechanism and kinetics of the pyrolysis reaction of the identified hemicellulose and lignin functionalities are then rigorously and systematically determined by the study of model molecules of incrementally increasing structural complexity, up to actual hemicellulose and lignin structures. Experimental and theoretical means are coordinated; A Thin Film Reactor obtains kinetically limited isothermal reaction rate and time-resolved evolved species information. Potential Energy Surfaces are determined by the M06-2X/6-311++G(d, p) methodology. This new fundamental knowledge is assimilated by the construction of detailed reaction kinetic models for hemicellulose, lignin and lignocellulose pyrolysis. The knowledge is disseminated for application in optimized and reduced models, envisaging their coupling to process and fluid dynamic engineering modelling tools.

Mots-clés : chemical reaction kinetics,kinetic model,lignocellulose,pyrolysis,lignin,hemicellulose
Projet ERC : LeibnizDream (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Humboldt-Universität zu Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2938750.0 €

Children around the globe acquire language and with it the human ability to communicate complex thoughts. This project develops a new linguistic theory to explain language and its acquisition. Our central hypothesis is that language radically compresses thought structures to sound or sign. While current theories assume a parallel between thought and language or meaning-preserving transformations, we assume that thought is mapped to language by only realizing some pieces of conceptual representations. Adult language is hyper-efficient at compressing information. For this reason, Leibniz and many others over the last 300 years have been unable to agree on the primitives of human thought. We predict that child languages are a better mirror of the human mind. Our initial evidence suggests that children are not able to compress conceptual representations as efficiently as adults. Sometimes children produce more material than adults, leading to so-called commission errors, which have never been systematically investigated. Furthermore, comprehension is easier for children when there is a one-to-one match between language and thought. To test our central hypothesis and specify how conceptual structure is compressed into language, we carry out a series of at least twelve targeted language acquisition studies on a global scale. We have recruited collaborators for more than 50 languages from 21 different language families, two sign languages and two creoles to carry out our studies. With this data, we can formulate a complete formal model of the semantic primitives, their combination into conceptual structures, the morphological compression mechanism, and the acquisition process within our model. To accomplish these goals, we rely on insights from formal semantics, generative syntax, distributed morphology, and several other linguistic frameworks. As part of our work, we also create the first open, global research collaboration to conduct language acquisition studies.

Mots-clés : first language acquisition,comparative linguistics,formal semantics,morphology,event structure
Projet ERC : SocSensors (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Children with autism and learning difficulties often need substantial support in schools and in later life with communication, emotion regulation and daily living skills. Teaching these children and measuring their progress in education is challenging. Our recent work (ERC grant INTERACT 313398) showed that tracking body motion in children and adults can give a real-world measure of how much people are engaged in a social interaction. In this project, we develop this result into a wearable sensor system to quantify and support children’s learning. In the SocSensor system, each child and teacher wears a sensor on their wrist (like a FitBit) and we track how they move in relation to each other, that is, their social engagement. This continuous monitoring is unobtrusive and is particularly valuable in understanding the behaviour of children with minimal verbal skills who cannot easily express themselves. Teachers and/or researchers can receive a report at the end of the lesson showing how often children were engaged and who interacted with who, which will allow them to monitor the effectiveness of lessons and compare different educational approaches. This will allow them to optimise learning opportunities for these-hard-to-reach children. The domains of educational technology and wearables are growing rapidly but no other product addresses the needs of children with autism and learning difficulties, so the SocSensors system can make a big impact. In this project, we will develop the interface for the SocSensors sensor system, collect validation data in a large autism school and build connections with business partners. This will move SocSensors from a lab prototype to a viable product, as well as showcasing the product to schools, teachers and the autism community. Thus, SocSensors will lead the way in using psychology and wearable computing to support engagement and learning in children with autism + learning difficulties.

Mots-clés : autism,wearable sensors,social interaction,education,learning difficulties
Projet ERC : FastEE (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : CNRS Innovation — Pays : France — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 12950.29 €

Chiral molecules exist as two forms, called enantiomers, which are mirror images of each other but which are not superimposable. Living organisms are built upon chiral elementary blocks. Biological processes can thus be extremely sensitive to chirality. Two enantiomers can have different smells or tastes. More critically, a chiral molecule can have healing properties while its mirror image is a poison. This makes the measurement of enantiomeric excess (EE), which quantifies the relative composition of the two images in a mixture, crucial for many industrial sectors: fragrance and food industry, pharmaceutics, agrochemistry. To improve product quality, lower health risks, and optimize processes to reduce chemical waste, it would be necessary to monitor EE continuously. Yet, this task is currently impossible because there is no fast and accurate enough EE measurement method. The FastEE project aims at solving this issue by using a new physical process which is extremely sensitive to chirality. By investigating the photoionization of chiral molecules by elliptically polarized light, we found out that the angular distribution of the ejected electrons carried rich information on the ionized molecules as well as their enantiomeric purity. Continuously modulating the ellipticity of the ionizing radiation while recording images of the photoelectron distribution enables the chemical composition and EE of mixtures to be followed in in real-time. FastEE aims at: (i) designing a demonstrator instrument using this method, optimized for an applicative environment, (ii) optimizing the method for the accurate analysis of complex chiral mixtures in real-time, (iii) investigating transfer and commercialization strategies. After completion of the three phases, we will be able to offer a new solution (instrument and methodology) for chiral analysis, enabling fast and continuous measurements with excellent accuracy - which is not possible with current technologies.

Mots-clés : enantiomeric excess measurements,chiral analysis,photoelectron circular dichroism
Projet ERC : EXCITERS (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
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 : 1691865.0 €

Chiral molecules exist as two forms, so-called enantiomers, which have essentially the same physical and chemical properties and can only be distinguished via their interaction with a chiral system, such as circularly polarized light. Many biological processes are chiral-sensitive and unraveling the dynamical aspects of chirality is of prime importance for chemistry, biology and pharmacology. Studying the ultrafast electron dynamics of chiral processes requires characterization techniques at the attosecond (10−18 s) time-scale. Molecular attosecond spectroscopy has the potential to resolve the couplings between electronic and nuclear degrees of freedom in such chiral chemical processes. There are, however, two major challenges: the generation of chiral attosecond light pulse, and the development of highly sensitive chiral discrimination techniques for time-resolved spectroscopy in the gas phase. This ERC research project aims at developing vectorial attosecond spectroscopy using elliptical strong fields and circular attosecond pulses, and to apply it for the investigation of chiral molecules. To achieve this, I will (1) establish a new type of highly sensitive chiroptical spectroscopy using high-order harmonic generation by elliptical laser fields; (2) create and characterize sources of circular attosecond pulses; (3) use trains of circularly polarized attosecond pulses to probe the dynamics of photoionization of chiral molecules and (4) deploy ultrafast dynamical measurements to address the link between nuclear geometry and electronic chirality. The developments from this project will set a landmark in the field of chiral recognition. They will also completely change the way ellipticity is considered in attosecond science and have an impact far beyond the study of chiral compounds, opening new perspectives for the resolution of the fastest dynamics occurring in polyatomic molecules and solid state physics.

Mots-clés : attosecond science,high order harmonic generation,photoelectron circular dichroism,chiral recognition,ultrafast molecular dynamics
Projet ERC : SC-EpiCode (Horizon 2020, appel 2016, Starting 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 : 1500000.0 €

Chromatin regulators adjust genome functions by modifying chromatin states. Comprehensive characterization of chromatin states, associations of chromatin regulators, and expression profiles is crucial for investigating: 1.Cellular differentiation triggers. 2.The nature of the underlying chromatin regulatory mechanisms. 3.The effect of cellular heterogeneity, and 4. How chromatin affects mRNA expression. Mapping chromatin states by sequencing immunoprecipitated chromatin (ChIP-seq) provides an extraordinary resource for studying cellular states. However, a major shortcoming is that the profiles reflect a composite average over the studied cell population, concealing important information about the underlying subpopulations. To address this hurdle, I pioneered Drop-Seq, a novel drop based microfluidic technology for single cell ChIP-seq and RNA-seq. Applying the technique to thousands of embryonic stem (ES) cells, we identified a spectrum of sub-populations defined by differences in chromatin signatures of pluripotency and differentiation priming. However, despite initial progress, the extent and significance of chromatin-state heterogeneity and its relationship with mRNA expression remain largely uncharted. The central aim of this proposal is to develop a novel framework to systematically characterize cell-to-cell variability at the epigenomic level. Our approach will include the development of technology enabling ChIP-seq and RNA-seq on the same cell. We will also exploit drop-based microfluidics to develop a robust CRISPR/Cas9-based approach to assess single and multiple perturbations. Finally, we will apply these innovative technologies to questions about cellular heterogeneity and epigenomic regulation during early differentiation of ES cells. This proposal will reveal the function and interplay between chromatin regulators, histone marks and transcription events, and shed light on the underlying regulation leading to cell fate decisions.

Mots-clés : epigenomics,chromatin,histone marks,chromatin regulators,cell to cell variation,embryonic stem cells,cellular differentiation,lineage commitment,single cell measurements
Projet ERC : ANEUPLOIDY (Horizon 2020, appel 2019, Synergy grants)
Entité participante : University of Zagreb — Pays : Croatie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499625.0 €

Chromosome segregation errors cause aneuploidy, a state of karyotype imbalance that accelerates tumor formation and impairs embryonic development. Even though mitotic errors have been studied extensively in cell cultures, the mechanisms generating various errors, their propagation and effects on genome integrity are not well understood. Moreover, very little is known about mitotic errors in complex tissues. The main goal of this project is to uncover the molecular origins of mitotic errors and their contribution to karyotype aberrations in healthy and diseased tissues. To achieve our goal, we have assembled an interdisciplinary team of experts in molecular and cell biology, cell biophysics, chromosomal instability in cancer, and theoretical physics. Our team will introduce novel approaches to study aneuploidy (superresolution microscopy, optogenetics, laser ablation, single cell karyotype sequencing) and apply them to state-of-the-art tissue cultures (mammalian organoids and tumoroids). In close collaboration, Tolić will establish assays to detect and quantify error types in cells, and Kops and Amon will use the assays on various healthy and cancer tissues. Tolić and Kops will uncover the molecular origins of errors, their propagation and impact on genome integrity, while Amon will lead the investigation of the mechanisms that ensure high chromosome segregation fidelity in healthy tissues. Interwoven in these collaborations are the efforts of Pavin, who will develop a theoretical model to describe the origin of errors and to quantitatively link chromosome segregation fidelity in single cells and tissues. Model and experiment will continuously inspire each other, to achieve deep understanding of how mitotic errors arise, how they propagate and how they impact on cell populations. Thus, the extensive sets of expertise present in our team will be combined and expanded with novel technologies to tackle the big challenge of the origins of aneuploidy in humans.

Mots-clés : chromosome segregation,aneuploidy,mitotic spindle,organoids,laser microsurgery,modeling
Projet ERC : ANEUPLOIDY (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Massachusetts Institute of Technology — Pays : Etats-Unis — Rôle : PI
Acronyme de l'entité : MIT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1177500.0 €

Chromosome segregation errors cause aneuploidy, a state of karyotype imbalance that accelerates tumor formation and impairs embryonic development. Even though mitotic errors have been studied extensively in cell cultures, the mechanisms generating various errors, their propagation and effects on genome integrity are not well understood. Moreover, very little is known about mitotic errors in complex tissues. The main goal of this project is to uncover the molecular origins of mitotic errors and their contribution to karyotype aberrations in healthy and diseased tissues. To achieve our goal, we have assembled an interdisciplinary team of experts in molecular and cell biology, cell biophysics, chromosomal instability in cancer, and theoretical physics. Our team will introduce novel approaches to study aneuploidy (superresolution microscopy, optogenetics, laser ablation, single cell karyotype sequencing) and apply them to state-of-the-art tissue cultures (mammalian organoids and tumoroids). In close collaboration, Tolić will establish assays to detect and quantify error types in cells, and Kops and Amon will use the assays on various healthy and cancer tissues. Tolić and Kops will uncover the molecular origins of errors, their propagation and impact on genome integrity, while Amon will lead the investigation of the mechanisms that ensure high chromosome segregation fidelity in healthy tissues. Interwoven in these collaborations are the efforts of Pavin, who will develop a theoretical model to describe the origin of errors and to quantitatively link chromosome segregation fidelity in single cells and tissues. Model and experiment will continuously inspire each other, to achieve deep understanding of how mitotic errors arise, how they propagate and how they impact on cell populations. Thus, the extensive sets of expertise present in our team will be combined and expanded with novel technologies to tackle the big challenge of the origins of aneuploidy in humans.

Mots-clés : chromosome segregation,aneuploidy,mitotic spindle,organoids,laser microsurgery,modeling