Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MemDense (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Saarland University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1934065.0 €

All cells must balance the production of proteins and lipids to maintain membrane functions. Imbalances in protein folding and lipid metabolism cause endoplasmic reticulum (ER) stress associated with a wide range of complex diseases including diabetes, neurodegeneration, and viral infections. The central homeostatic program of the ER is the unfolded protein response (UPR), which senses unfolded proteins in the ER to control protein synthesis, chaperone abundance, and lipid metabolism. Through these mechanisms, the UPR centrally controls decisions between cell survival, adaptation, and apoptosis. The field has focused almost exclusively on soluble proteins as triggers of the UPR, while the more abundant membrane proteins have been neglected. Our finding of UPR activation by membrane aberrancies provides a radically new perspective and allows us to address central questions in membrane and cell biology: How is the density of ER membrane proteins sensed and controlled? How are misfolded membrane proteins recognized to mount adaptive responses? Focusing on the conceptual advance that UPR transducers sense signals from the membrane, we will 1) establish and reconstitute the machinery for sensing membrane protein crowding, 2) identify mechanisms coordinating protein and lipid homeostasis between organelles, 3) study the molecular recognition of misfolded membrane proteins by the UPR. Key to this endeavor is our unique combination of genetic, biochemical, and biophysical tools for parallel characterization of the UPR in vivo and in vitro. Combining this framework with novel strategies for an immuno-isolation of organelles, we are primed to answer how membrane aberrancies cause chronic ER stress. By establishing the UPR as a quality control system for membrane proteins, and providing novel tools and valuable resources to the community, MemDense will have wide impact on our molecular and cellular understanding of ER homeostasis and the many diseases related to ER stress.

Mots-clés : membrane quality control,unfolded protein response,membrane protein crowding,lipid bilayer stress
Projet ERC : BIRD (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
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 : 2424186.0 €

All day long, our fingers touch, grasp and move objects in various media such as air, water, oil. We do this almost effortlessly - it feels like we do not spend time planning and reflecting over what our hands and fingers do or how the continuous integration of various sensory modalities such as vision, touch, proprioception, hearing help us to outperform any other biological system in the variety of the interaction tasks that we can execute. Largely overlooked, and perhaps most fascinating is the ease with which we perform these interactions resulting in a belief that these are also easy to accomplish in artificial systems such as robots. However, there are still no robots that can easily hand-wash dishes, button a shirt or peel a potato. Our claim is that this is fundamentally a problem of appropriate representation or parameterization. When interacting with objects, the robot needs to consider geometric, topological, and physical properties of objects. This can be done either explicitly, by modeling and representing these properties, or implicitly, by learning them from data. The main scientific objective of this project is to create new informative and compact representations of deformable objects that incorporate both analytical and learning-based approaches and encode geometric, topological, and physical information about the robot, the object, and the environment. We will do this in the context of challenging multimodal, bimanual object interaction tasks. The focus will be on physical interaction with deformable objects using multimodal feedback. To meet these objectives, we will use theoretical and computational methods together with rigorous experimental evaluation to model skilled sensorimotor behavior in bimanual robot systems.
Projet ERC : tRNAslation (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Jagiellonian University — Pays : Pologne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997500.0 €

All living cells employ messenger RNAs (mRNA), transfer RNAs (tRNA) and ribosomal RNAs (rRNA) to decode genomic information and synthesize the correct set of proteins at the right sub-cellular localization and at the right time. The attachment of specific chemical groups to individual RNA bases attributes novel chemical properties and strongly influences their functionality. In particular, modifications of the tRNA anticodon and critical regions of rRNAs are primed to influence the translation of individual mRNAs and tune the decoding behavior during ribosomal translation elongation. Individual ribosomes, mRNAs and tRNAs are dynamically decorated with different combinations of RNA modifications depending on the cell type, cellular compartment, metabolic state and environmental conditions. This additional layer of complexity creates specialized translational units and vastly expands the regulatory potential of the strictly conserved and almost invariant core translation machinery. Despite their key role in translation, most modification cascades and the functional interplay of the resulting RNA modifications during ribosomal decoding remain elusive. In the proposed project, we aim (i) to structurally characterize key RNA modification complexes, (ii) to create sets of fully modified RNAs in vitro, (iii) to understand the role of individual rRNA and tRNA modifications during translation elongation and (iv) to provide mechanistic insights into the unfortunate link between patient derived mutations of the underlying pathways and the onset of severe human diseases. In summary, we will extend the recently arising concept of “specialized ribosomes” by adding unique RNA modifications into the overall scheme. This project will provide deep molecular insights into fundamental processes, that are clinically relevant and which regulate, shape and orchestrate the cellular protein landscapes in all known organisms.

Mots-clés : protein synthesis,rrna,trna,modification,anticodon,elongator,thiolation,cancer,neurodegenerative diseases
Projet ERC : COGNAP (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Liège — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499125.0 €

All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.

Mots-clés : circadian regulation,neuroimaging
Projet ERC : COEVOPRO (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499275.0 €

All organisms in nature are targets for parasite attack. Over a century ago, it was first observed that symbiotic species living in hosts can provide a strong barrier against infection, beyond the host’s own defence responses. We now know that ‘protective’ microbial symbiont species are key components of plant, animal, and human microbiota, shaping host health in the face of parasite infection. I have shown that microbes can evolve within days to protect, providing the possibility that microbe-mediated defences can take-over from hosts in fighting with parasites over evolutionary time. This new discovery of an evolvable microbe-mediated defence challenges our fundamental understanding of the host-parasite relationship. Here, I will use a novel nematode-microbe interaction, an experimental evolution approach, and assays of phenotypic and genomic changes (the latter using state-of-the-art sequencing and CRISPR-Cas9 technologies) to generate new insights into the drivers and consequences of coevolving protective symbioses. Specifically, the objectives are to test: (i) the ability of microbe-mediated protection to evolve more rapidly than host-encoded resistance, (ii) the impacts of evolvable protective microbes on host-parasite coevolution, and the effect of community complexity, in the form of (iii) parasite and (iv) within-host microbial heterogeneity, in shaping host-protective microbe coevolution from scratch. Together, these objectives will generate a new, synthetic understanding of how protective symbioses evolve and influence host resistance and parasite infectivity, with far-reaching implications for tackling coevolution in communities.

Mots-clés : experimental evolution,coevolutionary biology,parasitism,mutualism
Projet ERC : CATCH (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Wageningen University & Research — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : WUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1995060.0 €

All primary chemical bonds, covalent and supramolecular, weaken under tension. This imposes fundamental limits on the mechanical stability of molecules and their materials. Nature has evolved to secondary bonds that break through these limits and strengthen under tension. These so-called catch bonds, which know no synthetic equivalent to date, are used in Nature as a rule, rather than exception, in scenarios where supramolecular bonds are exposed to large stresses. This change in the fundamental mechanical nature of bonds has a profound effect on the mechanics of the materials in which they are integrated. Yet, to date, there have been no systematic studies that establish how the mechanics of individual catch bonds is programmed by their chemical design or how their collective action results in enhanced mechanics of their materials. As a result, our understanding of the ubiquitous use of catch bonds in Nature is incomplete nor do we have clear guides how their potential can be harnessed in creating bio-mimetic soft materials with programmable mechanics. Project CATCH tackles these challenges by bringing catch bonds to the synthetic domain for the first time. Their de-novo creation gives unprecedented control to establish the design rules for the mechano-activity of single bonds. Moreover, CATCH will systematically explore how the concerted action of many catch bonds within a material lead to material properties that cannot be accessed by any other means, such as the adaptive reduction of strain localisation and the filtering of mechanical signals, which is of crucial importance for mechanical communication between cells in tissue engineering. Through a multidisciplinary approach that builds on my expertise in synthetic and materials chemistry, single-molecule experiments, and multiscale mechanical experiments and modelling, this project will decipher and harness one of Nature’s most ubiquitous, but poorly understood, mechanical design strategies.

Mots-clés : mechanochemistry,catch bonds,bio inspired materials
Projet ERC : 3DMOSHBOND (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : University of Leeds — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1971468.0 €

All properties of matter are ultimately governed by the forces between single atoms, but our knowledge of interatomic, and intermolecular, potentials is often derived indirectly. In 3DMOSHBOND, I outline a program of work designed to create a paradigm shift in the direct measurement of complex interatomic potentials via a fundamental reimagining of how atomic resolution imaging, and force measurement, techniques are applied. To provide a clear proof of principle demonstration of the power of this concept, I propose to map the strength, shape and extent of single hydrogen bonding (H-bonding) interactions in 3D with sub-Angstrom precision. H-bonding is a key component governing intermolecular interactions, particularly for biologically important molecules. Despite its critical importance, H-bonding is relatively poorly understood, and the IUPAC definition of the H-bond was changed as recently as 2011- highlighting the relevance of a new means to engage with these fundamental interactions. Hitherto unprecedented resolution and accuracy will be achieved via a creation of a novel layer of vertically oriented H-bonding molecules, functionalisation of the tip of a scanning probe microscope with a single complementary H-bonding molecule, and by complete characterisation of the position of all atoms in the junction. This will place two H-bonding groups “end on” and map the extent, and magnitude, of the H-bond with sub-Angstrom precision for a variety of systems. This investigation of the H-bond will present us with an unparalleled level of information regarding its properties. Experimental results will be compared with ab initio density functional theory (DFT) simulations, to investigate the extent to which state-of-the-art simulations are able to reproduce the behaviour of the H-bonding interaction. The project will create a new generalised probe for the study of single atomic and molecular interactions.
Projet ERC : BoostDiscovery (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1420000.0 €

Almost ten years into the highly successful program both in ATLAS and CMS, our understanding of the Standard Model (SM) of particle physics has deepened. Nonetheless, what lies beyond the SM remains one of the most urgent questions of physics in the 21st century. To move forward, one must think outside of the box and leap into uncharted waters. Searches today are aiming at the high-energy frontier, while low-mass resonances are mostly overlooked by the Large Hadron Collider (LHC). Consequently, far-reaching hints of new physics may silentlyhide in the data. Motivated by numerous New Physics (NP) scenarios that often predict light states, such as extended Higgs sectors, axion physics, or dark sector models, among others, the PI will develop new techniques to search for low-mass resonances decaying into two collimated low-pT hadronic τ leptons. τs, being the heaviest, third-generation leptons, provide a unique experimental opportunity to search for low-lying states that would otherwise go undetected. In particular, novel methods to identify boosted hadronic τ+τ− pairs will be established. These techniques will then be used to pave a new path towards discovery of low-mass resonances produced through various production modes. As part of this proposal, the PI will also develop new trigger-level capabilities to further extend the reach of this program at Run-3. As a former leader of the ATLAS Beyond the Standard Model physics group, and current leader of low-mass resonance searches, the PI is ideally positioned to establish a strong research team and take this project to completion, laying the groundwork for the discovery of new physics beyond the SM.

Mots-clés : atlas,physics beyond the standard model,beyond the standard models higgs searches
Projet ERC : WiHDE (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : University of Stuttgart — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149994.0 €

Altered muscle activity might be co-responsible for chronic pain. Discomfort, ache and reduced mobility are, for example, associated in low back pain patients with dysfunctional activation of the spine musculature often leading to a vicious circle of overloading and inactivity. Analysing the activities of relevant muscles in real time could provide valuable feedback for new therapies. However, deriving from muscular activities pathological behaviour requires the use of a high-density electromyographic (HD-EMG) device that precisely measures muscular activity during daily activities. A HD-EMG device that can be used in such a scenario, however, does not exist. The aim of this proof of concept is to deploy WiHDE, the first fully wearable HD-EMG device with wireless transmission and local storage capabilities, able to stream data directly towards computers or mobile devices, store it locally, or to perform on-board advanced signal processing operations in real-time while the subject can freely move around. WiHDE appears in the shape of a small, unobtrusive and discrete device, which can be placed on top or in the vicinity of an HD-EMG electrode array and allows to access the muscular activity with simplicity and precision. WiHDE is safe, energy and privacy-aware, and its modular nature favours advanced sensor fusion for unprecedented versatility of use. Within this ERC-PoC, we aim to develop such a HD-EMG device by investigating different business options and by enhancing current technology at the same time. This proposed device can be used in a clinical or similar setting, e.g., for neurophysiology-based applications such as (but not limited to) prostheses control, ergonomics, sport, rehabilitation, entertainment and, of course, basic motor control research. There is also an increasing interest in this technology from sports professional and advanced amateurs, who started realizing the importance of detailed muscular information to evaluate and improve their performance.

Mots-clés : wireless emg,high density,rehabilitation,sport,entertainment,ergonomics,prosthesis control,safety
Projet ERC : Fluodamage (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : CNRS Innovation — Pays : France — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 6800.0 €

Although elastomers are widely used in load-bearing engineering applications where lightweight and flexibility is essential, they are typically designed thicker than they need to be, due to a poor prediction of their lifetime in use. The loss of flexibility and extensibility results from individual covalent bond scission in the bulk of the material. When the extent of bond scission increases or localizes in specific spots, the rubber becomes brittle and can break catastrophically, potentially causing an accident. Detecting the early stage progressive molecular scale damage during use is impossible with current techniques using ultrasounds or X-rays. Within the framework of the ERC project CHEMECH we have precisely developed a method to detect, image and quantify bond breakage. This technique is based on tagging model materials with molecular probes (i.e., fluorophores) that become fluorescent when they break in response to a mechanical force. The goal of the current proposal is to incorporate the fluorophores in a variety of elastomers and to develop a novel methodology for non-destructive visualization and quantification of early damage by bond scission occurring in elastomers during cyclic mechanical testing. Compared to existing ultrasound and X-ray solutions, our technology detects degradation occurring at a much smaller scale (10 nm), can localize the damage more precisely and is non-destructive allowing the monitoring of the damage evolution in time. This information can then be used to refine the prediction of lifetime to design parts lighter and with less material, to schedule maintenance and part replacement more accurately, preventing catastrophic failures while saving time and money and finally to find new materials design strategies and expand the use of lightweight polymeric materials into new applications where they could replace metals or ceramics.

Mots-clés : organic chemistry,polymer physics,fracture mechanics,materials engineering,non destructve testing,fluorescence