Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Enhancer ID (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Research Institute of Molecular Pathology — Pays : Autriche — Rôle : PI
Acronyme de l'entité : IMP
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1999906.0 €

A major goal in biology is to understand how gene regulatory information is encoded by the human genome and how it defines different gene expression programs and cell types. Enhancers are genomic elements that control transcription, yet despite their importance, only a minority of enhancers are known and functionally characterized. In particular, their activity changes during cellular signalling or cell type transitions are largely elusive. Furthermore, fundamental questions about transcriptional co-factors have remained unanswered even though they regulate enhancer activities and have become attractive therapeutic targets, e.g. for cancer treatment. Here, I propose a functional genomics approach in mammalian cells with three specific objectives: First, we will identify and functionally characterize transcriptional enhancers in selected human and mouse cells using the recently developed quantitative enhancer activity assay STARR-seq. Second, we will determine enhancer activity changes quantitatively during steroid hormone signalling, cell differentiation, and malignant transformation to reveal enhancers that are important for these processes. Third, we will systematically dissect the functional relationship of enhancers and transcriptional co-factors. This proposal uses emerging in-house technology to address fundamental questions in enhancer biology and complement the genome-wide profiling of gene expression and chromatin states (e.g. by ENCODE). We will gain insights into the genomic organization of active enhancers and reveal chromatin or sequence features associated with dynamic activity changes. I also expect that we will be able to define co-factor requirements for enhancer function and reveal if different types of enhancers exist. Given our expertise in experimental and computational approaches and STARR-seq, I anticipate that we reach our aims and make major contributions to the understanding of gene regulation in mammals.

Mots-clés : enhancers,crms,transcriptional co factors,transcription factors,transcription factor motifs,functional enhancer assays,starr seq
Projet ERC : Gradual_Change (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Freie Universität Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2390598.0 €

A major goal in ecology is to predict how environmental changes, including drivers of global change, affect communities and ecosystem functioning, with society demanding answers to these pressing questions. A key limitation of virtually all experimental approaches addressing such questions is that treatments are delivered abruptly, while many changes occurring in nature are gradual. Here I propose to comprehensively study consequences of environmental change when delivered abruptly vs. gradually. In order to understand and model effects of gradual vs. abrupt changes, we need to simultaneously consider physiological effects (e.g. acclimation), evolutionary changes (e.g. adaptation) and changes in community composition and functioning. Even though changes at these levels likely interact, there is no study in which physiology, evolutionary changes and community shifts have been studied in response to a changing environmental factor. This research program thus enters unchartered territory of empirical environmental research in proposing work at this nexus of physiology, environmental change and community composition/ function. I focus on soil fungi, key players in terrestrial ecosystems, testing a range of gradually vs. abruptly changing environmental factors, in a range of soils, in the field and in microcosms. We connect differential responses to species traits, apply modeling and employ data syntheses across all biomes and organisms to achieve high external validity. We carry out a set of core experiments that will afford unprecedented insight into the nature of change in a community context in response to warming, focusing on soil fungi. In these we follow evolutionary change (phenotype and genotype), test physiological shifts by re-isolation of fungi and monitor community changes. This work will have transformative character in providing not only new mechanistic insights into effects of environmental change, but will also represent a step change in fungal ecology.

Mots-clés : global change
Projet ERC : KiloNeurons (Horizon 2020, appel 2020, Synergy grants)
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 : 2765000.0 €

A major goal in neuroscience is to understand neural computation in the mammalian cortex. Since the 1950s, we have learnt how cells respond to changes in the environment but the cells have largely been observed one at a time. However, single-cell recording cannot access the complexity of distributed processing and coding in the large, intermixed cell populations of the cortex. To understand this complexity, we need population-wide activity measurements, at single-cell resolution, as well as theoretical models to interpret the data. In this project, we shall combine experiments and theory to enable a paradigmatic shift from single-cell to population analysis for a prototypical high-level cortical system, the navigation system of the mammalian medial entorhinal-hippocampal region. In this system, spatial firing correlates of individual cells are so evident that they have been given simple, descriptive names – such as place cells, grid cells, and head direction cells. The wealth of information on the phenomenology of these cells, and the existence of theoretical frameworks that offer strong predictions on their population-wide activity patterns, renders the system perfect for population-level analyses of cortical computation. We shall introduce experimental tools to obtain the amount and specificity of multi-neuron data required to decipher neural population codes in freely navigating rodents. Guided initially by theory on attractor network dynamics, we shall identify regularities in firing and connectivity patterns of thousands of simultaneously monitored neurons and use the data to test, refine and develop theoretical models. This exercise will be extended to less-understood high-end systems such as lateral entorhinal cortex, where computational operations have remained elusive due to the lack of similar single-cell correlates. The project is transformative in that it will uncover fundamental and general mechanisms of high-end cortical population coding in mammals.

Mots-clés : computational neuroscience,entorhinal cortex,hippocampus,attractor networks,continuous attractors,grid cells,head direction cells,cortex,neural networks,spatial computation
Projet ERC : FANO (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Technical University of Denmark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : DTU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

A new class of devices exploiting Fano resonances and with important applications in information technology is suggested. Typically, the resonance of a system is described by a frequency and a lifetime, leading to a Lorentzian lineshape function. If the system instead involves interference between a discrete resonance and a continuum, a Fano lineshape appears with fundamentally different characteristics. Here, the Fano resonance is used to make a novel integrated mirror, enabling realization of Fano lasers, Fano switches and quantum Fano devices. These devices challenge well-accepted paradigms for photonic devices. The goals of the project are to demonstrate a laser with modulation bandwidth greatly exceeding all existing lasers; a nanolaser with linewidth three orders of magnitude smaller than existing nanocavity lasers; and a switch that operates at femtojoule energies and provides gain. Such devices are important for realizing high-speed optical interconnects and networks between and within chips. An increasing fraction of the global energy consumption is being used for data communication, and photonics operating at very high data rates with ultra-low energy per bit has been identified as a key technology to enable a sustainable growth of capacity demands. Existing device designs, however, cannot just be scaled down to reach the goals for next-generation integrated devices. The Fano mirror will also be used to demonstrate control at the single-photon level, which will enable high-quality on-demand single-photon sources, which are much demanded devices in photonic quantum technology. These devices all rely on the unique properties of the Fano mirror, which provides a new resource for ultrafast dynamic control, noise suppression and ultra-low energy operation. Using photonic crystal technology the project will achieve its goals in a concerted effort involving development of new theory, new nanofabrication techniques and advanced experiments.

Mots-clés : nanophotonics,semiconductor lasers,photonic crystals,optical signal processing,ultrafast dynamics
Projet ERC : xMEMSDBS (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : KTH Royal Institute of Technology — Pays : Suède — Rôle : PI
Acronyme de l'entité : KTH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

A new disposable sampling device that allows quantitative measurements from Dried Blood Spots (DBS) has been developed with support of the ERC AdG xMEMS. The technology consists of a small microfluidic chip made of laminated structured plastic foils and paper with the specific function to meter and store an exact blood volume as a DBS. The chip can be used directly by a patient to leave a capillary blood sample straight from a finger prick. This simplifies blood sampling, offers comfort for the patient and reduces costs for health care providers. In this project we shall perform activities to: Have a first complete product (proposed within TDM) that works for users and is backed up by clinical test(s). A company is formed, the business plan is worked out in detail and it is ready for a next financing round. IPR strategy has been chosen and patent(s) on blood as well as plasma are secured accordingly. We have worked out and tested a scalable and cost-efficient manufacturing and packaging strategy. We have chosen, prepared and acquired our first paying customer. We are ready to sell and have a plan for how to grow sales for defined product(s).

Mots-clés : microfluidics,material integration,bioanalysis,blood sampling
Projet ERC : PROSPER (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : PI
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499995.0 €

A new picture of our own ancestral past has emerged through the elucidation of the complex evolutionary relationships between Neanderthals, Denisovans, and modern humans. How preceding hominin populations fit into their story is currently unknown, but it has become clear that Pleistocene hominin populations were highly diverse. In addition to Homo erectus and Homo antecessor, they also include recently described populations such as the Denisovans, Homo floresiensis, Homo luzonensis, and Homo naledi, and previously known but elusive populations such as Homo heidelbergensis. These hominins were present across Africa and Eurasia, with large portions of the hominin fossil record far beyond the reach of ancient DNA research. It is therefore difficult to understand the distribution in time and space of these hominin populations, and elucidate their relation to the emergence of novel hominin behaviours evident in the archaeological record, using traditional approaches. Palaeoproteomic analysis of skeletal proteomes has recently emerged as a potential alternative biomolecular approach across the Pleistocene, and can provide independent molecular evidence on hominin evolutionary relationships on a global scale. PROSPER will make this opportunity a reality by developing novel sampling and extraction protocols for ancient skeletal proteomes, thereby minimizing the destructive sampling of highly unique, often fragmentary, hominin fossils, while simultaneously maximizing the proteomic data generated. With these methods available, PROSPER will generate unique insights into the evolutionary relationships between Pleistocene hominins across their African and Eurasian distribution, including the emergence and dispersal of our own species, Homo sapiens. PROSPER will be able to settle phylogenetic debates on hominin population relationships in a unique, novel manner, and can be expected to open up new avenues of research in palaeoanthropology.

Mots-clés : palaeoproteomics,human evolution,proteomics,phylogenetics,osteoarchaeology
Projet ERC : TORCH (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2585170.0 €

A new type of combustor architecture for large gas turbines has emerged in recent years: sequential combustion systems operated at constant pressure. This major technology change results from the need for more operationally and fuel flexible gas turbines, for future sustainable energy networks. As for regular gas turbines, the risk of combustor breakdown due to thermoacoustic instabilities is a major challenge. While the harmful consequences of these instabilities in novel sequential combustors can be as dramatic as in conventional systems, the associated physics is considerably complexified, because the two flames not only “talk” together via sound waves, but also via entropy waves. Our aim is to propose, investigate and develop novel active and passive control technologies, tailored for this new generation of combustors, in order to suppress their thermoacoustic instabilities. It brings significant scientific challenges in fluid mechanics, acoustics, combustion, nonlinear dynamics and control theory. We will address the problem of controlling these instabilities on two unexplored fronts: First, we intend to significantly move forward the state-of-the-art in passive control of combustion instabilities, by creating acoustic metamaterials with unprecedented acoustic damping properties, and capable of long term operation in harsh environments. Second, we plan to address scientific challenges, required to successfully achieve active combustion control in sequential combustors, by distributing non-equilibrium plasma discharges to locally and dynamically enhance the autoignition chemistry. To achieve these ambitious goals, a combination of experimental, numerical and theoretical methods will be applied with the aim to ultimately establish the potential and limitations of these novel technologies. This research deals with new areas in the field of thermoacoustics, and builds upon the PI’s scientific expertise in combustion and acoustics and on his technological know-how.

Mots-clés : gas turbine,combustion,acoustics,thermoacoustic instabilities,acoustic metamaterials,plasma assisted combustion
Projet ERC : WIRELESS (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Parma — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499338.0 €

A number of studies demonstrated that the primates’ premotor cortex (PM) plays a crucial role not only in organizing movement, but also in perceptual and socio-cognitive functions. However, these studies have been carried out in laboratory settings, which deeply limit the possibility to understand the neural mechanisms underlying natural behaviours. To solve this problem, I propose a new approach consisting in a two-steps chronic recording of monkey PM neurons: first, single neurons response properties will be characterized in a traditional, head-restrained laboratory setting; then, in the same session, the same neurons activity will be recorded wirelessly during free interactions of the monkey with its physical and social environment. The project will initially focus on neurons belonging to the forelimb representation of the ventral (i.e. areas F4 and F5) and dorsal (area F2vr) PM, putatively well known for their role in sensorimotor transformations, goal coding, representation of space, and recognition of other’s observed actions. The same paradigm will then be applied to the study of the mesial pre-supplementary area F6, a crucial bridge between prefrontal and PM regions whose role in socio-cognitive functions remains still virtually unknown. Finally, by simultaneous, chronic recording of neuronal activity from lateral and mesial PM, we will first assess the functional interactions between these areas in both laboratory and natural settings, and then we will probe causality in these interactions by chemically manipulating neuronal activity of one region (i.e. F6) while recording from the other one (i.e. F5). The project will reveal the role of premotor cortex in motor and social functions during natural behaviours. In addition, it might open up new possibilities for future studies of neural plasticity and reorganization of ethologically-relevant motor, cognitive and social functions following chemical manipulation of neural activity and virtual brain lesions.

Mots-clés : mirror neurons,sensorimotor transformation,action prediction,wireless recording,free behaviour,decision,action selection
Projet ERC : GlobalBioIm (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499515.0 €

A powerful strategy for increasing the quality and resolution of medical and biological images is to acquire larger quantities of data (Fourier samples for MRI, projections for X-ray imaging) and to jointly reconstruct the complete signal by correctly reallocating the measurements in 3D space/time and integrating all the information available. The underlying image sequence is reconstructed globally as the result of a very large-scale optimization that exploits the redundancy of the signal (spatio-temporal correlation, sparsity) to improve the solution. Due to recent advances in the field, we are arguing that such a “bigger data” integration is now within reach and that our team is ideally qualified to lead the way. A successful outcome will profoundly impact the design of future bioimaging systems. We are proposing a unifying framework for the development of such next-generation reconstruction algorithms with a clear separation between the physical (forward model) and signal-related (regularization, incorporation of prior constraints) aspects of the problem. The pillars of our formulation are: an operator algebra with a corresponding set of fast linear solvers; an advanced statistical framework for the principled derivation of reconstruction methods; and learning schemes for parameter optimization and self-tuning. These core technologies will be incorporated into a modular software library featuring the key components for the implementation and testing of iterative reconstruction algorithms. We shall apply our framework to improve upon the state of the art in the following modalities: 1) phase-contrast X-ray tomography in full 3D; 2) structured illumination microscopy; 3) single-particle analysis in cryo-electron tomography; 4) a novel multipose fluorescence microscopy; 5) real-time MRI, and 6) a new multimodal digital microscope. In all instances, we shall work in close collaboration with the imaging scientists who are in charge of the instrumentation.

Mots-clés : statistical modeling,optical imaging,tomography,bio medical imaging
Projet ERC : LOCOMOUSE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Champalimaud Foundation — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1496750.0 €

A remarkable aspect of motor control is our seemingly effortless ability to generate coordinated movements. How is activity within neural circuits orchestrated to allow us to engage in complex activities like gymnastics, riding a bike, or walking down the street while drinking a cup of coffee? The cerebellum is critical for coordinated movement, and the well-described, stereotyped circuitry of the cerebellum has made it an attractive system for neural circuits research. Much is known about how activity and plasticity in its identified cell types contribute to simple forms of motor learning. In contrast, while gait ataxia, or uncoordinated walking, is a hallmark of cerebellar damage, the circuit mechanisms underlying cerebellar contributions to coordinated locomotion are not well understood. One limitation has been the difficulty in extracting quantitative measures of coordination from the complex, whole body action of locomotion. We have developed a custom-built system (LocoMouse) to analyze mouse locomotor coordination. It tracks continuous paw, snout, and tail trajectories in 3D with unprecedented spatiotemporal resolution and it has allowed us to identify specific, quantitative locomotor elements that depend on intact cerebellar function. Here we will combine this quantitative behavioral approach with electrophysiology and optogenetics to investigate circuit mechanisms of locomotor coordination. We will 1) Optogenetically silence the output of cerebellar subregions to understand their distinct contributions to locomotion. 2) Record from identified neurons and correlate their activity with specific locomotor parameters. 3) Optogenetically stimulate defined cell types to investigate circuit mechanisms of coordinated locomotion. These experiments will establish causal relationships between neural circuit activity and coordinated motor control, a problem with important implications for both health and disease.

Mots-clés : cerebellum,locomotion,coordination,optogenetics,electrophysiology