Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : TWIST (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : European Organization for Nuclear Research — Pays : Suisse — Rôle : PI
Acronyme de l'entité : CERN
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

TWIST will build detector modules for PET scanners that offer high sensitivity together with precise position and time resolution. TWIST will deliver high-resolution PET images with low background using a lower dosage of radio-tracer. The breakthrough is obtained due to the successful development of the new Strip Silicon PhotoMultiplier (SSiPM) within the ERC TICAL project. PET (Positron Emission Tomography) scanners create images of the distribution of positron emitters in the body of subjects under investigation. PET scans have a fundamental advantage over other forms of medical imaging, such as CT scans; since they are sensitive to the functioning of biological processes. Biomarkers are involved in chemical reactions active in molecular pathways of interest for diagnosing diseases; the image will alter according to molecular changes occurring within the area of interest. Since the imaging technique operates at the sub-cellular and molecular level of the body, it is known as molecular imaging. Although PET imaging is a very powerful diagnostic tool, an injection of a radiotracer is required. The precise time resolution of the TWIST modules with substantially reduce the background generating clearer images. The image resolution will be further enhanced due to the determination of the 511 keV gamma interaction point (including the depth of interaction). Since the depth of interaction is well determined, longer crystals can be used and the detection modules can be mounted close to the subject being scanned. This results in higher resolution images with a significant reduction (at least x5) use of radio tracer. For all developments, it is important to move from tests in the laboratory to building a system of multiple units, because this is the stage that these new developments become useful and open up commercial possibilities. The creation of a business plan to manufacture modules on a commercial basis is integrated within this proposal.

Mots-clés : medical imaging,precise timing,gamma detection,advanced electronics
Projet ERC : IMPACCT (Horizon 2020, appel 2018, Proof of concept grants)
Entité participante : Centre for Genomic Regulation — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG;CRG-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 145000.0 €

Targeted precision medicine combined with companion diagnostics will provide the basis for future more effective more economic patient care. Recent advances in breast cancer treatment combining inhibitors of poly-ADP-ribose polymerase (PARP1) in conjunction with other targets are at the forefront of this new advance both at the level of basic research and pharmaceutical interest, due to its pivotal role in gene expression, chromatin and repair. We have discovered a key enzyme downstream of PARP1 which generates ATP locally in the nucleus; NUDIX5. This enzyme is overexpressed in cancer and correlates with poor prognosis, as the activity of this enzyme is essential for changes within the 3D chromatin structure, gene regulation and the proliferation of cancer cells. We have developed inhibitors of NUDIX5 in addition to a companion diagnostic, and propose to prove using a multi-disciplinary, international collaborative effort that they can be used to determine not only patient risk and treatment options but also provide an exciting new avenue for the combinatorial treatment of breast and (we hope) other cancer patients.

Mots-clés : cancer biomarker,precision medicine,genomics,3d chromatin structure,multi disciplinary,systems biology,structural biology,molecular biology,lead compound validation,companion diagnostic,syg6 synergy panel 6
Projet ERC : FLE-X (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Italian Institute of Technology — Pays : Italie — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Techniques for non-destructive and non-invasive inspections are more and more required in our society, in different areas such as medical, industrial and security. X-ray radiation and its detection is the current inspection tool, coupled with electronic systems to gather information. However, while the electronic has gone through an impressive development to respond more and more to the need of a capillary presence in our life, without disturbing perception, the X-ray detection has remained behind. Thus, Users are limited to costly, cumbersome, fragile and extremely heavy detection devices, which do not allow nor extension to large areas neither easy integrability/conformability to a large variety of objects. FLE-X will develop the prototype of a low cost, flexible direct x-ray detector for imaging applications, which can be customized. It will be suitable for large areas inspections, and bendable around complex objects. It will be easy to handle. This will be achieved by developing printed thin films (<< 100 um) fabricated from lead-halides perovskites inks. Such device does not exist on the market. Once transformed into a commercial product, it will enable a shift paradigm for the X-ray detection market and will be a gate for new applications. To make this happen, FLE-X will identify the first process flow compatible with industrialization, will deliver a prototype of flexible X-ray imager and will provide a model and business plan which will allow an efficient technology transfer.

Mots-clés : x ray detector,perovskites,flexible electronics
Projet ERC : ORGANOMICS (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 328212.65 €

Technologies to sequence single-cell transcriptomes (scRNA-seq) are revolutionizing our ability to analyze cell composition and differentiation in complex tissues. In parallel, recent innovations allow the generation of three-dimensional tissues from stem cells that recapitulate human development. In this proposal, we will focus on human cortex development modelled by cerebral organoids. Our vision is to create an integrative single-cell transcriptomic platform to reconstruct cerebral organoid development, and dissect network alterations that lead to human brain malformations. Our project will be advanced through the following objectives: 1. Single-cell transcriptome-coupled lineage tracing: We will use cellular barcoding to label individual cortical progenitor cells, trace their output and lineage trees with high-throughput scRNA-seq, and quantify lineage transition probabilities between cell types. 2. Gene knockout screens in mosaic organoids: We will use CRISPR/Cas9 to perform genetic screens of up to 100 genotypes in mosaic organoids to understand mechanisms that regulate cell lineage decisions during cortex development. 3. High-throughput reconstructions of cortex malformations: We will generate cerebral organoids from patients with cortical malformations and reconstruct networks and infer differentiation hierarchies using high-throughput and lineage-coupled scRNA-seq. We will spatially resolve network aberrations using sequential fluorescence in situ hybridization (seqFISH). ORGANOMICS provides an entirely new quantitative direction to study human corticogenesis. We will build high-resolution models of cortex development by measuring the expression and function of genes in thousands of single cells. Our interdisciplinary project will lead to groundbreaking insight into mechanisms underlying neurodevelopmental diseases. Our general strategy can be extended to various other organ systems where protocols to generate in vitro counterparts can be established.

Mots-clés : single cell genomics,organoid technology,crispr,cas screen,cortical malformations
Projet ERC : Scale-FreeBack (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
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 : 2810575.0 €

Technology achievements were typically built upon fundamental theoretical findings, but nowadays technology seems to be evolving faster than our ability to develop new concepts and theories. Intelligent traffic systems benefit from many technical innovations, for example. Mobile phones, radars, cameras and magnetometers can be used to measure traffic evolution and provide large sets of valuable data. Vehicles can communicate with the network infrastructure, as well as each other. However, these huge technological advances have not been used to the full so far. Traffic lights are far from functioning optimally and traffic management systems do not always prevent the occurrence of congestions. So what is missing? Such systems affect our daily life; why aren’t them on pace with technology advances? Possible because they have become far more complex than the analytical tools available for managing them. Systems have many components, communicate with each other, have self-decision-making mechanisms, share an enormous amount of information, and form networks. Research in control systems has challenged some of these features, but not in a very concerted way. There is a lack of “glue” relating the solutions to each other. In the Scale-FreeBack project, it is proposed to approach this problem with a new holistic vision. Scale-FreeBack will first investigate appropriate scale-free dynamic modeling approaches breaking down system’s complexity, and then develop control and observation algorithms which are specifically tailored for such models. Scale-FreeBack will also investigate new resilient issues in control which are urgently required because of the increasing connectivity between systems and the external world. Road traffic networks will be used in proof-of-concept studies based on field tests performed at our Grenoble Traffic Lab (GTL) and in a large-scale microscopic simulator.
Projet ERC : SHELTERINS (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Spanish National Cancer Research Centre — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CNIO
Type d'entité : Recherche
Financement ERC de l'entité : 2495466.0 €

Telomeres are protective structures at the chromosome ends essential for genome stability. Telomere biology is intricately linked with human cancer. Most cancer cells reactivate telomerase to avoid telomere loss associated to cell division. Targeting telomerase inhibition in cancer has shown very limited efficacy, alternative or additional mechanisms of telomere maintenance are thus at play in cancer. Recent evidence shows that components of the telomere-protecting shelterin complex are mutated in cancer. Shelterin prevents chromosome fusions, impedes persistent DNA damage response at telomeres and regulates telomerase activity. We were first in describing shelterin mutations in cancer and pioneered the idea of targeting shelterin as an anticancer strategy to induce length-idependent telomere damage. We also found that key cancer pathways regulate shelterin function throughout post-transcriptional modifications. Developing new therapeutic approaches based on targeting shelterin is hampered by lack of mouse models and incomplete understanding of which underlying mechanisms mutations in shelterin drive tumour development. We strive to establish a comprehensive set of tools, to enable us to conduct a fundamental and far-reaching experimental programme on the role of shelterin in cancer. Our specific aims are to i) generate knock-in mice to understand the role of POT1 shelterin mutations found in cancer and develop personalized therapeutic strategies based on these alterations, ii) generate knock-in mice to understand the role of post-translational modifications of the TRF1 shelterin by several cancer pathways for the identification of new cancer targets, and iii) dissect the potential role of TRF1 in cancer stem cells. We expect to block the ability of cancer cells to divide indefinitely and effectively impair cancer growth. Our research programme will reveal the role of two fundamental aspects of biology, telomere capping and chromosomal stability, in cancer.

Mots-clés : telomeres,cancer,telomere integrity,cancer stem cells,shelterin proteins,mouse models,pot1 mutations,trf1 post translational modifications,crispr cas9 technology
Projet ERC : INHIBITHUMAN (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1796038.0 €

Temporal co-ordination of the activity of cortical neurons underlies cognitive processes. Intracortical inhibitory circuits set temporal windows for modulation of glutamatergic pyramidal cell firing. In non-human mammals, the activity of the GABAergic neurons is governed by other specialised GABAergic neurons, which can dis-inhibit pyramidal cells. The overarching aim of this project is to define cellular and pharmacological mechanisms of dis-inhibitory circuits in the human cerebral cortex. These circuits could act as regulators of cognitive process. First, we will investigate the neuron types and their synaptic influences to characterise how dis-inhibition controls synaptic integration and the output of neurons. Second, we will elucidate synaptic plasticity in dis-inhibitory circuits, as plastic events likely represent physiological substrates of cognitive operations. Third, we will identify the subcellular sites and the mechanisms of action of key receptors for ACh, monoamines, endocannabinoids, neuropeptides and mGluRs modulating dis-inhibitory circuits, which are targets of small molecule CNS drugs, such as cognitive enhancers. We will test three hypotheses: 1) the human cortical pyramidal cell output is gated by compartment-specific dis-inhibition mediated by specific interneurons; 2) activity-dependent plasticity occurs in dis-inhibitory circuits and has consequences for the output of cortical pyramidal neurons; 3) small molecule drugs act via dis-inhibitory mechanisms at cell-type specific sites altering the inhibitory dynamics of pyramidal cells leading to subcellular redistribution of inhibition and alteration in their output. Combined electrophysiology/imaging with neuropharmacology and high resolution molecular receptor localisation will generate an unprecedented knowledge of the human cortical circuits. Understanding human cortical neuronal connections and their responses to pharmacological interventions may also lead to novel therapeutic strategies.

Mots-clés : interneuron,gaba,cerebral cortex,electrophysiology,synaptic transmission,synaptic receptors
Projet ERC : LifeWithoutInsulin (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Geneva — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIGE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Tens of millions suffer from insulin deficiency (ID); a condition caused by pancreatic β-cell loss. If untreated, ID is a lethal catabolic disease characterized by hyperglycemia. Thus, the focus of ID research and drug development has been mainly on improving strategies to lower hyperglycemia without causing life-threatening hypoglycemia. However, in addition to increased circulating glucose level β-cell loss leads to several “other defects”, some of which (e.g. severe hyperketonemia and ketoacidosis) are life-threatening. Therefore, it is important to develop strategies that in addition to improve hyperglycemia can also rescue the “other defects” (e.g. increased ketogenesis) caused by ID. For example, we have recently published results underscoring the importance of ameliorating hyperglycemia and the “other defects”. Indeed, our data indicate that despite the presence of slightly improved hyperglycemia a normalization of hyperketonemia and hypertriglyceridemia is associated with a significant extension in lifespan of mice with β-cell loss (https://www.nature.com/articles/s41467-019-11498-x). Untreated ID rapidly leads to death. However, since insulin was discovered in the early 1920s, ID has been treated with insulin therapy; an approach that converted this lethal disease into one a person can live with. Yet, insulin therapy is unsatisfactory. Indeed, ID subjects have higher risks for developing kidney failure, blindness, nerve damage, heart attack, stroke, and hypoglycemia. Some of these defects are favored by insulin therapy itself. Our goal is to diminishing the amount of insulin dosage and hence reducing the risks associated with insulin therapy (e.g. life-threatening hypoglycemia). The present application aims at providing a composition for improving the treatment of ID. If successful, we will be able to commercialize our composition and improve therapy in millions suffering from ID.

Mots-clés : insulin deficiency,therapy,insulin,combination therapy
Projet ERC : CLOTHILDE (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Universitat Politècnica de Catalunya — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : UPC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 305125.0 €

Textile objects pervade human environments and their versatile manipulation by robots would open up a whole range of possibilities, from increasing the autonomy of elderly and disabled people, housekeeping and hospital logistics, to novel automation in the clothing internet business and upholstered product manufacturing. Although efficient procedures exist for the robotic handling of rigid objects and the virtual rendering of deformable objects, cloth manipulation in the real world has proven elusive, because the vast number of degrees of freedom involved in non-rigid deformations leads to unbearable uncertainties in perception and action outcomes. This proposal aims at developing a theory of cloth manipulation and carrying it all the way down to prototype implementation in our Lab. By combining powerful recent tools from computational topology and machine learning, we plan to characterize the state of textile objects and their transformations under given actions in a compact operational way (i.e., encoding task-relevant topological changes), which would permit probabilistic planning of actions (first one handed, then bimanual) that ensure reaching a desired cloth configuration despite noisy perceptions and inaccurate actions. In our approach, the robot will learn manipulation skills from an initial human demonstration, subsequently refined through reinforcement learning, plus occasional requests for user advice. The skills will be encoded as parameterised dynamical systems, and safe interaction with humans will be guaranteed by using a predictive controller based on a model of the robot dynamics. Prototypes will be developed for 3 envisaged applications: recognizing and folding clothes, putting an elastic cover on a mattress or a car seat, and helping elderly and disabled people to dress. The broad Robotics and AI background of the PI and the project narrow focus on clothing seem most appropriate to obtain a breakthrough in this hard fundamental research topic.

Mots-clés : assistive robotics,robotic manipulation,deformable object modeling,learning from,demonstration,computational topology,rgb d vision,probabilistic planning,textile industry,clothing business
Projet ERC : ThoriumNuclearClock (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 5739635.0 €

Th-229 has an exceptionally low-energy excited nuclear isomer state with an excitation energy of only a few electron volts, making it accessible to laser manipulation. With a predicted relative radiative linewidth of 1e-19, constructing a Thorium nuclear clock becomes possible that could rival todays most advanced optical atomic clocks. The few-eV transition emerges from a fortunate near-degeneracy of the two lowest nuclear energy levels. However, the Coulomb and strong-force contributions to these level energies differ on the MeV level. This makes the Th-229 nuclear level structure uniquely sensitive to variations of fundamental constants and ultralight dark matter. Very recently, the applicants have proven the long-sought existence of the low-energy isomer, determined the lifetime in different electronic environments, quantified the nuclear moments and charge radius based on the hyperfine splitting, and constrained the isomer energy. However, knowledge on the electronic and nuclear properties is still insufficient to exploit the Th-229 system for fundamental tests. This project aims to close this gap and realize three prototype nuclear Thorium clocks using complementary approaches in trapped ions and solids. We will develop customized VUV laser systems and perform precision spectroscopy of the Th-229 nuclear transition. Comparing these clocks among each other and with state-of-the-art optical clocks will allow us to benchmark the new frequency standard before ultimately applying it to test fundamental physics. This project requires a unique combination of experimental and theoretical expertise in atomic and nuclear physics, high precision metrology and fundamental symmetries. Furthermore, special infrastructure is required for (distributed) clock comparison, precision spectroscopy as well as processing of Th-229. The synergy team is composed to optimally respond to these challenges while being rooted in established and successful collaborations.

Mots-clés : atomic clocks and frequency standards,fundamental constants,dark matter search