Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : uDAS (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Bar-Ilan University — Pays : Israël — Rôle : PI
Acronyme de l'entité : BIU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Microfluidic systems, in general, have proven important platforms for biomedical assays. These systems benefit from reduced requirements for expensive reagents, short analysis times, and portability. Although microfluidic systems are convenient platforms, their use in the life sciences is still limited mainly due to the high-level fabrication expertise required for construction. Integrated microfluidics is one of the most sophisticated three-dimensional (multi layer) solution. It requires soft lithography (PDMS based chips), for production of high complexity microfluidic systems (multiple serial or parallel processes). Integrated microfluidics in particular is almost non-existent in the industry due to the low yield and uncontrolled production process. My ERC project (MUDLOC-2012) is to develop a microfluidic platform for multidimensional protein array analysis. It uses complex multilayer microfluidic devices that consist of 2 PDMS layers and a glass microarray. The integrated microfluidics system contains thousands of micromechanical valves in micrometer dimensions, controlling thousands of parallel reactions. Our research demands production of hundreds of such devices. We, as all others who produce integrated microfluidics, suffered from frustrating low yield (15%). In order to improve fabrication yield and to fabricate devices with increased density, we designed and manufactured, a first of its kind, full production process sequence, semi automatic Microfluidic Device Assembly System (µDAS). This resulted in a direct increase of device complexity and yield (85%) over the last half year. The 2nd generation automated µDAS prototype will become a generic assembly tool for soft lithography. µDAS will enable a critical production standard and process control, which will pave the road for significant penetration of complex integrated microfluidics technology into both academia and industry.

Mots-clés : integrated microfluidics,lab on chip,production process control
Projet ERC : REM (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Bilkent University — Pays : Turquie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Microfluidics technology has been quite successful in fabricating small, low-cost devices with excellent analyte handling capabilities. However, the main detection paradigm in microfluidics has still been optical microscopy — which is a bulky and expensive technique. A chip-scale detection scheme that can provide multidimensional information is much needed for the widespread adoption of lab-on-a-chip technology. So far, successful capacitive and resonant electrical sensors have been deployed in the field; yet the focus of these sensors has been to obtain the electrical volume or location of a particle — which constitutes only a limited piece of information about the analytes. Here we propose to redesign and utilize resonant electrical sensors in a radically different way to obtain images of cells in a microfluidic channel. The technique proposed can also multiplex on-chip cytometry greatly, accomplish low-cost and high-throughput single-cell transit-time characterization, obtain not only the electrical but also the geometrical size of analytes, determine the dielectric permittivity of analytes, in addition to capturing 1D profile or 2D images of cells. At the basic science level, the project will enhance our understanding of the interaction of electromagnetic fields and living matter at the single cell level and may provide new insights on cell motility, growth and mechanics.

Mots-clés : lab on a chip
Projet ERC : ComplexSwimmers (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Bilkent University — Pays : Turquie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

Microswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equilibrium physics underlying the adaptive and collective behavior of biological entities such as chemotactic bacteria and eukaryotic cells. From the more applied side, they provide tantalizing options to perform tasks not easily achievable with other available techniques, such as the targeted localization, pick-up and delivery of microscopic and nanoscopic cargoes, e.g., in drug delivery, bioremediation and chemical sensing. However, there are still several open challenges that need to be tackled in order to achieve the full scientific and technological potential of microswimmers in real-life settings. The main challenges are: (1) to identify a biocompatible propulstion mechanism and energy supply capable of lasting for the whole particle life-cycle; (2) to understand their behavior in complex and crowded environments; (3) to learn how to engineer emergent behaviors; and (4) to scale down their dimensions towards the nanoscale. This project aims at tackling these challenges by developing biocompatible microswimmers capable of elaborate behaviors, by engineering their performance when interacting with other particles and with a complex environment, and by developing working nanoswimmers. To achieve these goals, we have laid out a roadmap that will lead us to push the frontiers of the current understanding of active matter both at the mesoscopic and at the nanoscopic scale, and will permit us to develop some technologically disruptive techniques, namely, targeted delivery of cargoes within complex environments, which is of interest for drug delivery and bioremediation, and efficient sorting of chiral nanoparticles, which is of interest for biomedical and pharmaceutical applications.

Mots-clés : microswimmers,active brownian motion,far from equilibrium physics
Projet ERC : INsPIRE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Université Paris-Saclay — Pays : France — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1277500.0 €

Mid-infrared (mid-IR) spectroscopy is a nearly universal way to identify chemical and biological substances, as most of the molecules have their vibrational and rotational resonances in the mid-IR wavelength range. Commercially available mid-IR systems are based on bulky and expensive equipment, while lots of efforts are now devoted to the reduction of their size down to chip-scale dimensions. The demonstration of mid-IR photonic circuits on silicon chips will benefit from reliable and high-volume fabrication to offer high performance, low cost, compact, low weight and power consumption photonic circuits, which is particularly interesting for mid-IR spectroscopic sensing systems that need to be portable and low cost. In this context, the INsPIRE project will address a new route towards key advances in the development of chip-scale integrated circuits on silicon for the mid-IR wavelength range. The original idea is to use nonlinear optical properties in Ge/SiGe quantum well (QW) active devices combined with Ge-rich-SiGe waveguides. The objectives of the INsPIRE project are far beyond the state of the art, by targeting the monolithic integration of passive and active devices for operation in the 3 to 15 µm wavelength range. As a main cornerstone we will demonstrate an optical photonic circuit based on Ge/SiGe QWs relying on a mid-IR light emitter combined with a mid-IR spectrometer and a detector array. The integration will be performed using Ge-rich-SiGe waveguides allowing the extension of the wavelength range up to 15 µm. Such demonstration, which will constitute a breakthrough for establishing chip-scale circuits for the mid-IR photonics, requires a deep knowledge and understanding of Ge/SiGe optical properties. In particular, second- and third-order nonlinear optical properties of Ge/SiGe QW structures will be investigated in a wide spectral range from 3 to 15 µm.

Mots-clés : mid infra red,silicon photonics,germanium,quantum wells
Projet ERC : MINORITYRULE (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Cologne — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Minority rule is a frequent phenomenon in many parliamentary democracies. In minority governments, political parties in cabinet neither enjoy majority support in the electorate nor in parliament. Minority rule has become more prevalent in a time when party systems in democracies are experiencing drastic changes. Citizens’ voting behavior has become more volatile, new challenger parties – including populist radical right parties – have permanently entered the political landscape, and parliaments have become more fractionalized. The implications of the increasing phenomenon of minority rule for the functioning of democracy and political representation are possibly far-reaching. Unfortunately, existing theoretical and empirical approaches are insufficient to understand the consequences of minority rule for party systems, governmental behavior, and citizens’ responses. MINORITYRULE’s objective is therefore to provide a broad and systematic comparative analysis of the implications of minority rule for political representation. The project investigates how minority rule affects the intensity of political polarization between political parties during parliamentary debates and election campaigns, how it constrains the responsiveness of governments to public opinion at the national and European level, and how citizens evaluate the legitimacy of minority rule. MINORITYRULE will accomplish these tasks on the basis of an unprecedented comparative data collection using novel multilingual text-as-data approaches and cross-national survey experiments. Ultimately, the project will lead to a new theory of political representation under minority rule. In light of changing party systems, MINORITYRULE will generate new insights about the nature of political representation in which governments rule without stable majorities in parliament and society.

Mots-clés : political representation,minority governments,responsiveness,public opinion,text as data,survey experiments
Projet ERC : MSAG (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2434492.0 €

Mirror symmetry is a phenomenon first discovered by string theorists in 1989. This phenomenon, when described in mathematical language, posits that certain kinds of geometric objects, known as Calabi-Yau manifolds, come in pairs X, Y. Further, mirror symmetry posits an intricate relationship between the geometry of the members of the pair. This relationship can be summarized by the rough statement that the symplectic geometry of X is isomorphic to the complex geometry of Y. Mathematical explorations of mirror symmetry have led to deep and profound insights in algebraic, logarithmic, symplectic and differential geometry, as well as algebraic combinatorics and representation theory. Working with Siebert, I have developed a program (colloquially referred to as the Gross-Siebert program) for exploring the underlying geometry of mirror symmetry using methods from algebraic and tropical geometry. I propose to use the techniques developed with Siebert to make significant breakthroughs in our understanding of mirror symmetry. Recently, we gave a general mirror construction for log Calabi-Yau pairs and maximally unipotent degenerations of Calabi-Yau manifolds. This allows the possibility of dramatic progress in the subject. The construction of a mirror goes by way of the construction of its coordinate ring. These coordinate rings can be viewed as the degree zero part of a `relative quantum cohomology ring.' I plan to generalize the construction of this ring to all degrees. A proof of mirror symmetry at genus zero could then be realised by constructing an isomorphism between this ring and the ring of polyvector fields of the mirror. I will also use the new constructions of mirrors to develop powerful new methods for constructing algebraic varieties, and I will develop a range of practical techniques for understanding the mirrors constructed. I also propose to explore a range of other enumerative invariants in the context of the Gross-Siebert program.

Mots-clés : mirror symmetry,gromov witten theory,tropical geometry
Projet ERC : MitO2Health (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Ulm — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999363.75 €

MitO2Health aims to develop and empirically prove a radically new pathophysiological model of Major Depressive Disorder (MDD) as a systemic energy deficiency disease. Traditionally, MDD is conceptualized as a neurotransmitter deficiency in the brain. However, with pioneering methods my group has provided evi-dence for reduced mitochondrial energy production in MDD, characterizing it as a cellular-metabolic disorder with a lowered production of adenosine triphosphate (ATP). Reduced mitochondrial bioenergy production and impairments in oxygen (O2) homeostasis (reduced levels of erythrocytes, less hemoglobin and its lower O2-binding affinity due to oxidative stress), as well as oxidative stress and inflammation (the “MitO2Health parameters”) were consistently associated with an increased risk for MDD, but have been neglected so far in MDD research and therapy. In MitO2Health we will more comprehensively than ever before investigate the physiological mechanisms underlying MDD and will provide first longitudinal evidence on the mutual in-terplay between the MitO2Health parameters and MDD. Moreover, we will apply cognitive-behavioral therapy (CBT) as randomized treatment condition to test whether CBT-related MDD symptom reduction is coupled to a normalization of the MitO2Health parameters. We will treat 100 MDD patients with 6 months of CBT and compare them to 100 MDD patients of a waiting-list group and 100 healthy controls. Clinical and biological status will be assessed at four points over 18 months. We will thus characterize the biomarker pro-files of MDD treatment response and resistance as well as MDD symptom recurrence during a follow-up pe-riod. MitO2Health will not only establish a modern etiological model of MDD, but also identify biomarkers of individual therapy response and relapse. This will lead to new diagnostic standards and inspire personalized MDD treatment concepts that will fundamentally improve clinical outcomes in psychotherapy and psychiatry.

Mots-clés : clinical psychology,stress,chronic and traumatic stress,depression,major depressive disorder,inflammation,oxidative stress,mitochondria
Projet ERC : SynapticMitochondria (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Lisbon — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1300000.0 €

Mitochondria at the synapse have a pivotal role in neurotransmitter release, but almost nothing is known about synaptic mitochondria composition or specific functions. Synaptic mitochondria compared to mitochondria in other cells, need to cope with increased calcium load, more oxidative stress, and high demands of energy generation during synaptic activity. My hypothesis is that synaptic mitochondria have acquired specific mechanisms to manage local stress and that disruption of these mechanisms contributes to neurodegeneration. How mitochondria sense their dysfunction is unclear. Even more intriguing is the question how they decide whether their failure should lead to removal of the organelle or dismissal of the complete neuron via cell death. We anticipate that these decisions are not only operational during disease, but might constitute a fundamental mechanism relevant for maintenance of synaptic activity and establishment of new synapses. Recent studies have revealed several genes implicated in neurodegenerative disorders involved in mitochondrial maintenance. However the function of these genes at the synapse, where the initial damage occurs, remains to be clarified. These genes provide excellent starting points to decipher the molecular mechanisms discussed above. Furthermore I propose to use proteomic approaches to identify the protein fingerprint of synaptic mitochondria and to compare them to mitochondria from other tissues. I plan to identify key players of the proposed regulatory pathways involved in intrinsic mitochondria quality control. In a complimentary approach, I will exploit our findings and use in vitro and in vivo experimental approaches to measure mitochondrial function of synaptic versus non-synaptic mitochondria and the relevance of those changes for synaptic function. Our work will unravel the specific properties of synaptic mitochondria and provide much needed insight in their hypothesized predominant role in neurodegenerative disorders.

Mots-clés : mitochondria,synapse,neurodegeneration
Projet ERC : MISTRANSMITO (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Helsinki — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1354507.5 €

Mitochondria play a central role in the energy metabolism of our bodies and their defects give rise to a large variety of clinical phenotypes that can affect practically any tissue. The mechanisms for the tissue-specific outcomes of mitochondrial diseases are poorly understood. Mitochondrial energy production relies on two separate protein synthesis machineries, cytoplasmic and mitochondrial, but the mechanisms regulating the concerted actions between the two are largely to be discovered. Defects in either protein synthesis system that lead to accumulation of mistranslated mitochondrial proteins, intrinsic or imported from the cytoplasm, result in stress signals from mitochondria and in adaptive responses within the organelle and the entire cell. My hypothesis is that some of these signals and adaptive mechanisms are tissue-specific. My group will test the hypothesis by 1) generating and characterizing mouse models of cytoplasmic and mitochondrial mistranslation to be able to address our questions in different tissues. 2) We will develop methods for detection of ribosome stalling in mouse tissues to identify the consequences of mistranslation for individual proteins. 3) We will use systems biology approaches to identify stress signal responses to mitochondrial and/or cytoplasmic mistranslation using different tissues of our models, to identify those that are unique or global. 4) Our previous study has identified an interesting candidate responder to mistranslation stress and we will test the role of this factor in knockout animal models and by crossing with the mistranslation mice. I expect to gain important new knowledge of in vivo responses to mistranslation and execution of quality control. This proposal investigates key questions in understanding differential tissue involvement in metabolic defects, and will provide new directions for utilization of tissue-specific adaptations in finding interventions for mitochondrial diseases.

Mots-clés : mistranslation,mitochondria,aminoacyl trna synthetase
Projet ERC : Mito-recombine (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1473732.0 €

Mitochondrial DNA (mtDNA) is a multi-copy genome that works with the nuclear genome to control energy production and various cellular processes. To date, disorders associated with mutations in mtDNA are among the most common genetically inherited metabolic diseases1. However, our knowledge regarding many aspects of mtDNA biology remains limited, and we know even less about how it influences development and organismal traits. This is largely due to our inability to manipulate mtDNA. Recently, a colleague and I developed novel genetic tools in Drosophila that allowed us to isolate animal mitochondrial mutants for the first time, and to create heteroplasmic organisms containing two mitochondrial genotypes2,3. These advances make Drosophila a powerful system for mtDNA studies. Importantly, I showed that Drosophila mtDNA could undergo homologous recombination. Furthermore, I established a system to induce recombination at specific sites and select for progeny containing only the recombinant genome4. Thus, my work has demonstrated the existence of recombination in animal mitochondria, and opens up the possibility of developing a recombination system for functional mapping and manipulating animal mtDNA. Here I propose to 1) identify components of the mitochondrial recombination machinery by a candidate RNAi screen; 2) develop a recombination toolkit to map trait-associated mtDNA sequences/SNPs; and 3) build a site-directed mutagenesis system by establishing robust ways to deliver DNA into fly mitochondria. Given the essential functions of mitochondria and their involvement in incurable diseases, the genetic tools developed in this proposal will transform the field by making it possible to link mtDNA variations to phenotypic differences and introduce specific mutations into mtDNA for functional studies at organismal level. These advances will open many possibilities to accelerate our understanding on how mtDNA impacts health, disease and evolution.