Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : AAA (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
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 : 1175902.5 €

Although we have extensive knowledge of many important processes in cell biology, including information on many of the molecules involved and the physical interactions among them, we still do not understand most of the dynamical features that are the essence of living systems. This is particularly true for the actin cytoskeleton, a major component of the internal architecture of eukaryotic cells. In living cells, actin networks constantly assemble and disassemble filaments while maintaining an apparent stable structure, suggesting a perfect balance between the two processes. Such behaviors are called “dynamic steady states”. They confer upon actin networks a high degree of plasticity allowing them to adapt in response to external changes and enable cells to adjust to their environments. Despite their fundamental importance in the regulation of cell physiology, the basic mechanisms that control the coordinated dynamics of co-existing actin networks are poorly understood. In the AAA project, first, we will characterize the parameters that allow the coupling among co-existing actin networks at steady state. In vitro reconstituted systems will be used to control the actin nucleation patterns, the closed volume of the reaction chamber and the physical interaction of the networks. We hope to unravel the mechanism allowing the global coherence of a dynamic actin cytoskeleton. Second, we will use our unique capacity to perform dynamic micropatterning, to add or remove actin nucleation sites in real time, in order to investigate the ability of dynamic networks to adapt to changes and the role of coupled network dynamics in this emergent property. In this part, in vitro experiments will be complemented by the analysis of actin network remodeling in living cells. In the end, our project will provide a comprehensive understanding of how the adaptive response of the cytoskeleton derives from the complex interplay between its biochemical, structural and mechanical properties.
Projet ERC : aLzINK (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université de Toulouse — Pays : France — Rôle : Partner
Acronyme de l'entité : UT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 57831.25 €

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

Mots-clés : bio inorganic chemistry,peptides,copper,zinc,aggregation,ligands
Projet ERC : AD-VIP (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Alzheimer’s disease (AD) is the most common form of dementia in the Western World, representing an economic and social cost of billions of euros a year. Given the changing demographics of society, these costs will only increase over the coming decades. Amyloid plaques, composed of amyloid beta peptide (Abeta), are a defining characteristic of AD. Evidence now suggests that Abeta is central to disease pathogenesis due to its toxicity, which leads to cell loss and eventual cognitive decline. Abeta is generated by proteolytic cleavage of amyloid precursor protein, a process that involves the protein BACE1. Knock-down of BACE1 is sufficient to prevent amyloid pathology and cognitive deficits in transgenic mouse models of AD, so BACE1 is an attractive target for therapeutic intervention. Although many small molecule inhibitors of BACE1 have been developed, many have problems with imperfect selectivity, posing a substantial risk for off-target toxicity in vivo. In contrast, antibody-based therapeutics provide an attractive alternative given their excellent molecular selectivity. However, the success of antibody therapies in AD is limited by the blood brain barrier, which limits antibody entry into the brain from the systemic circulation. Recent studies have shown that adeno-associated virus serotype 9 (AAV9) effectively crosses the blood brain barrier. Here, we propose evaluating the use of AAV9 as a delivery system for a highly specific and potent inhibitory nanobody targeted against BACE1 as a treatment for AD.

Mots-clés : adeno associated virus  aav  based vector,blood brain barrier crossing,nanobody,bace1
Projet ERC : CatASus (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Graz — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 62500.0 €

Amines are crucially important classes of chemicals, widely present in pharmaceuticals, agrochemicals and surfactants. Yet, surprisingly, a systematic approach to obtaining this essential class of compounds from renewables has not been realized to date. The aim of this proposal is to enable chemical pathways for the production of amines through alcohols from renewable resources, preferably lignocellulose waste. Two key scientific challenges will be addressed: The development of efficient cleavage reactions of complex renewable resources by novel heterogeneous catalysts; and finding new homogeneous catalyst based on earth-abundant metals for the atom-economic coupling of the derived alcohol building blocks directly with ammonia as well as possible further functionalization reactions. The program is divided into 3 interrelated but not mutually dependent work packages, each research addressing a key challenge in their respective fields, these are: WP1: Lignin conversion to aromatics; WP2: Cellulose-derived platform chemicals to aromatic and aliphatic diols and solvents. WP3: New iron-based homogeneous catalysts for the direct, atom-economic C-O to C-N transformations. The approach taken will embrace the inherent complexity present in the renewable feedstock. A unique balance between cleavage and coupling pathways will allow to access chemical diversity in products that is necessary to achieve economic competitiveness with current fossil fuel-based pathways and will permit rapid conversion to higher value products such as functionalized amines that can enter the chemical supply chain at a much later stage than bulk chemicals derived from petroleum. The proposed high risk-high gain research will push the frontiers of sustainable and green chemistry and reach well beyond state of the art in this area. This universal, flexible and iterative approach is anticipated to give rise to a variety of similar systems targeting diverse product outcomes starting from renewables.
Projet ERC : MycoVAP (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 : 149625.0 €

Among 65-80% of human infections are associated to biofilms, especially in respiratory infections or those associated with catheters. Endotracheal tube (ETT) biofilm is related to the development of ventilator-associated pneumonia (VAP), which occurs in 9–27% of all intubated patients. Those ETT-biofilms are mainly formed by Pseudomonas aeruginosa and/or Staphylococcus aureus, forming a protective barrier against antibiotics and the host immune system. The consequence of VAP is chronic inflammation resulting in slow but continuous decrease of lung function, which is the primary cause of mortality of patients at hospital wards, and is also associated with increased hospital morbidity; duration of hospitalization and consequently health care costs. Engineering bacteria to deliver locally therapeutic agents or to present antigens for vaccination is an emerging area of research with great clinical potential. Up to date, an attenuated BCG strain, used for prostate cancer vaccination, is the only example of a living bacteria used for human therapy. However, there are several studies worldwide at preclinical stage addressing the use of engineered bacteria for human therapy. We suggest here to test a non-pathogenic chassis of the mild human lung pathogen Mycoplasma pneumoniae, engineered to dissolve biofilms of S. aureus and P. aeruginosa for the treatment of VAP. The specific objectives of this proposal are: First, to confirm the safety of our bacterial chassis in the lung of animal models (mice and pigs). Second, to test the capacity of our engineered chassis to eliminate bacterial biofilms formed in endotracheal tubes and in mice models of biofilm formation. Success in both objectives will open the way to test our chassis in pig models of VAP as a first step towards its application in humans.

Mots-clés : biofilm,lung infection,bacterial therapy,synthetic biology
Projet ERC : MathAm (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Université Catholique de Louvain — Pays : Belgique — Rôle : Partner
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 421645.0 €

Among the most important mathematical quantities of interest in high-energy particle physics are the so-called scattering amplitudes, which allow us to make predictions for physical observables. Despite their importance, performing explicit computations of scattering amplitudes is still one of the bottlenecks of high-energy physics, mostly due to the complexity of the integrals involved and a lack of understanding of the underlying mathematics. Over the last couple of years, a deep connection between scattering amplitudes and certain branches of modern mathematics has slowly started to emerge. The goal of MathAm is investigate in detail the relationship between scattering amplitudes, number theory and algebraic geometry, with the final aim of developing novel computational techniques for scattering amplitudes that are beyond reach of conventional state-of-the-art technology. The ultimate goal of MathAm is threefold: By revealing unexpected connections between seemingly disconnected areas of mathematics and physics, MathAm will 1. shed new light on the mathematical underpinnings of the fundamental laws of Nature in general. 2. play a decisive role in testing recent conjectures about the all-loop structure of certain special classes of gauge 3. theories by confronting them to the explicit results for scattering amplitudes, 3. set a new standard for making predictions for collider experiments like the LHC by performing computations that are beyond reach of current technology. To sum up, MathAm has a unique multi-disciplinary character and, by applying novel technology from modern mathematics, its results will have impact in various seemingly disconnected disciplines, ranging from the frontiers of research in pure mathematics over formal aspects of Quantum Field Theory all the way to making the most precise theoretical predictions for the LHC experiments.

Mots-clés : scattering amplitudes,feynman integrals,number theory,algebraic geometry
Projet ERC : STEMCARDIORISK (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Leiden University Medical Center — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : LUMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Among the most significant conceptual changes in stem cell biology of the past decade has been the use of human pluripotent stem cells (hPSCs) for disease modelling and drug development rather than solely as therapeutics. One area of major interest in this context is that of arrhythmic disorders of the heart. Cardiac arrhythmias are a leading cause of death among young people, with inherited forms affecting as many as 1 in 2000. Even more prevalent are acquired arrhythmias due to adverse responses to medication. These too have a significant heritable component. Although hundreds of mutations have been associated with both forms of arrhythmia, two outstanding issues remain: (i) it is difficult to prove the identified mutation is causal, and (ii) large differences in disease severity are seen even among patients with the same primary mutation. To date hPSC models of arrhythmogenic diseases exhibit the characteristic electrophysiological features of the respective disorders; however lack of appropriate controls and inherent variability between hPSC lines means that it is still unclear how well these models reflect the genotype-phenotype relationship. This proposal will combine hPSC disease modelling with recent advances in gene-editing, plus the wealth of genomic data associating genetic variants to disease phenotypes, to develop unique approaches that will 1) establish the sensitivity of these models and; 2) provide more accurate functional assessment of the contribution of individual variants to congenital and acquired arrhythmias. I believe that by creating panels of isogenic PSC lines differing exclusively at candidate genetic loci we can (i) predict the pathogenicity of variants; (ii) shed light on the mechanism underlying the disease phenotype, and (iii) improve individual risk stratification and patient-specific pharmacotherapy. This study will also offer a first entry into interpreting GWAS and capitalising on the value of the human genome sequencing projects.

Mots-clés : human pluripotent stem cells,disease modelling,gene targeting,inherited cardiac arrhythmia
Projet ERC : RESHAPE (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Università Campus Bio-Medico — Pays : Italie — Rôle : PI
Acronyme de l'entité : UCBM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1490750.0 €

Amputation distorts the body representation, a fundamental aspect of self-consciousness. Hand prostheses counteract sensorimotor impairment, but poor attention has been posed to target the alteration of body-image. RESHAPE aims to study prosthesis embodiment, identify what makes a hand prosthesis easily embodiable, and test non-invasive brain stimulation to facilitate the embodiment. Amputees claim to perceive prostheses as tools; RESHAPE enables amputees to project their self into the prosthesis, improving in parallel their dexterity. The first of three phases develops the enabling technology and defines the embodiment protocol. The following phase evaluates thirty myoelectric-prosthesis users and the first of two amputees implanted with peripheral neural electrodes, for functional ability, prosthesis embodiment and acceptability and for phantom limb pain (PLP), before and after neuromodulation. In the last phase, a neuro-controlled prosthesis is optimized in line with the specifications defined in the previous phase and tested in the second implanted amputee. An embodiment and a sensory/manipulation platform, integrating a discrimination setup with sensorized wearable systems, induce and weigh the embodiment and its impact on prosthesis performance. Embodiment neural correlates are investigated with EEG and fMRI-based techniques, thanks to a prosthesis virtual model controllable inside the scanner. Patients are stimulated with a homeostatic plasticity-based rTMS either on premotor cortex or on intraparietal sulcus. A robot-aided TMS compensates head-coil relative displacement, allowing the subject to operate the prosthesis during the stimulation. RESHAPE is a paradigm shift in Prosthetics. It offers the guidelines for highly-embodiable prostheses, four technological platforms beyond the state-of-the-art, novel insights on how tools shape the body-image, the proof of a TMS-induced embodiment and a new strategy to readdress amputees’ aberrant plasticity and PLP.

Mots-clés : neuroprosthetics,embodiment,non invasive brain stimulation,brain plasticity,invasive peripheral interfaces,hand performance monitoring
Projet ERC : MRI4DEEG (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 137500.0 €

An EEG calibration toolkit for monitoring rehabilitation of stroke patients EEG records electric potential differences from electrodes attached to the human skin. Since it is a brain imaging technique that provides a direct measure of neural activity, it is an ideal device to monitor stroke rehabilitation. For instance, the amplitude of an EEG response to a fixed external stimulus on the wrist could act as a biomarker quantifying the number of active cells in the primary somatosensory cortex. In this way, an EEG system could work as a simple monitoring device rendering direct feedback to healthcare workers on the success of the applied therapeutic strategy. This would greatly help to select the most optimal therapy for the individual patient. However, with the current state of the art a direct comparison between EEG amplitudes of different subjects is not possible because these amplitudes are strongly affected by inter individual skull variations. In this PoC project a calibration step is proposed to reduce these influences on the EEG biomarker. We will develop a software toolkit, allowing to execute the required calibration step with a minimum of patient burden. We foresee that the prototype delivered by the end of the project can be developed into a commercial accessory EEG software device that can be provided to end users for relatively small add-on price. Best practices of EEG calibration will be disseminated by publications, presentations at conferences, a special workshop and business development activities.

Mots-clés : head models,conductivity,stroke
Projet ERC : PLAMORF (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 2525000.0 €

An essential consequence of multi-cellularity is the need for intercellular and tissue wide communication. As seen with animals, higher plants coordinate metabolic and developmental processes via signals transferred to different body parts. Plants use a dual vascular system consisting of phloem and xylem for long-distance transfer of metabolites and signalling molecules. In contrast to circular systems in animals, transport in flowering plants occurs in the phloem via the cytoplasm of connected cells devoid of nuclei. In addition to small molecules, a remarkably large number of so-called mobile micro RNAs (miRNAs), messenger RNAs (mRNAs), and phloem RNA-binding proteins (RBPs) were identified in the phloem and in chimeric plants. Mobile RNAs and RBPs move through plasmodesmata into and through the phloem to distinct tissues. Thus, mobile RNAs represent an additional class of signalling molecules, raising important questions in the field of intercellular signalling. This project combines the expertise of three research groups in the fields of cell biology/macromolecular transport, mathematical modelling/bioinformatics and phloem function/protein biochemistry. It addresses the questions: How are mobile miRNAs and mRNAs selected for transport? Is this process specific and regulated by RBPs and motifs? What determines their destination? And importantly, how are these signals processed in the destination cells? To address these questions, we will develop predictive models, using novel single cell transcriptomics pipelines to establish cell-type specific RNA transport and motifs (WP1), and studying the structure, affinity, and functions of phloem RBPs to gain insights in the RNA delivery mechanism (WP2). We will combine the advantages of the agronomically important plant oilseed rape to identify phloem RNAs and RBPs with the well-established A. thaliana model that allows us to identify and test cell-specific transported RNA signals and RBPs in a time-efficient manner.

Mots-clés : single cell transcriptomics,macromolecular signals,rna binding proteins,rna motifs,messenger rna transport,inter cellular communication,phloem,micro rna,chimeric plants