Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ICLUb (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Dundee — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 228405.41 €

The overall objective of this proposal is to understand, on an atomic level, the mechanism of activation and regulation of the Fanconi Anemia (FA) DNA repair pathway. Homozygous mutations in the FA pathway lead to Fanconi Anemia, a devastating childhood genome instability disorder, typified by bone marrow failure and a high predisposition to cancers. The FA pathway is required for the repair of DNA interstrand crosslinks (ICLs), the hallmark of many cancers and FA. ICL repair is poorly understood on a biophysical and mechanistic level. The FA pathway is regulated by ubiquitin, in a cycle of monoubiquitination and deubiquitination of FANCD2. Despite considerable advances in our understanding of the genetics of the pathway, there is strikingly little known on a mechanistic and chemical level concerning how the ubiquitin signal is assembled, recognised and disassembled. We will define, on an atomic level, the site-specific monoubiquitination and deubiquitination cycle of FANCD2 in its entirety. We will determine the mechanism of FANCD2 monoubiquitination, identify and characterise currently unknown readers of the monoubiquitin signal, define the role of the core complex in the modification of FANCD2, and the requirements for removal of the signal. To tackle this ambitious work we will determine the atomic level three-dimensional structure of key complexes in the modification cycle, and develop a novel method for producing large quantities of stably modified FANCD2. The results of our work will represent a major breakthrough in our knowledge and understanding of the regulation of a critical DNA repair process, will provide a model for understanding mechanisms of monoubiquitination, and will open up both therapeutic potential and new pathways for research into the cause and cure of FA, cancers, and aldehyde-induced liver or bone marrow failure.

Mots-clés : ubiquitin,posttranslational modification,fanconi anemia
Projet ERC : BRILLIANCE (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : European synchrotron radiation facility — Pays : France — Rôle : PI
Acronyme de l'entité : ESRF
Type d'entité : Recherche
Financement ERC de l'entité : 1430275.0 €

The overarching goal of this project is to establish a novel technique for neuroimaging to probe large tissue volumes at the nanometre scale. Currently only electron microscopes are capable of generating data with sufficient resolving power for comprehensive exploration of the neural circuits that underlie brain function. With state of the art systems, imaging just one cubic mm of brain entails years of data collection, ultra-thin sectioning which is prone to errors and data loss, and prohibitive costs. Each circuit unit spans over large distances, thus access to millimetre sized volumes of view is essential for both fundamental and therapeutic discoveries in neurosciences. Today this is an unreachable goal. In contrast, X-ray microscopy facilitates rapid imaging of large samples but the resolving power is not sufficient to visualize neural connections. Thus, at present, resolving large neural circuits is hardly imaginable. The aim of this project is to overcome these limitations and to develop an integrative approach which will open new research perspectives. X-ray holographic nano-tomography is a 3D coherent imaging technique which is capable of generating exceptional contrast in soft tissue through phase contrast. The penetrating power of X-rays and the full-field, free space propagation setup enable rapid multiscale imaging of large samples which are opaque to visible light. By combining a highly brilliant X-ray nanoprobe, a carefully designed nanopositioning system, a cutting edge detection system and cryogenics for sample preservation, isotropic 3D spatial resolution better than 30 nm is conceivable. The objectives of this interdisciplinary project are to 1) develop a system for imaging neural circuits at synaptic level in large tissue volumes, including methods for sample preparation, image acquisition and image reconstruction 2) develop an automatic image analysis tool 3) create unprecedented maps of brain circuits with immediate impact in neurosciences.

Mots-clés : x ray phase contrast microscopy,nanoimaging,neuroimaging,image reconstruction,cryomicroscopy,connectomics,neural networks,machine learning,holography,image segmentation
Projet ERC : SHADE (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497672.0 €

The past four years have witnessed dramatic discoveries surrounding the birth of gravitational wave astronomy. By their nature, gravitational waves are ideal probes with which to test the laws of gravity – something currently under scrutiny due to unresolved questions about the dark sector of the universe. In this proposal I lay out an ambitious campaign to determine the behaviour of gravity over cosmological distances, using the upcoming surge of gravitational wave data. I will achieve this by developing the burgeoning technique of `Statistical Host Identification’ of gravitational wave sources. This new tool will enable me to test gravity using hundreds of future detections of binary black holes at high redshifts, even without direct redshift information – thus removing a major obstacle for gravitational wave cosmology. I will phrase my constraints in terms of model-independent parameters that quantify physically viable deviations from General Relativity, making my results applicable to virtually any dark energy or extended gravity model. In this way, I can validate or eliminate the space of theories in current literature. To model the distribution of gravitational wave events and their host galaxies, I will construct an approximate simulation that operates with generalised, model-independent gravitational laws – the first ever simulation to do this. This tool enables me to additionally use information about gravity from non-linear scales of cosmological structure. This regime is virtually untouched by current comparable work, and is a prime target for the next generation of galaxy surveys. My key objectives are: i) To develop the calculations and software tools needed to apply gravitational wave Statistical Host Identification, in theories of gravity beyond General Relativity; ii) To use these tools to obtain powerful new constraints on extended gravity models, thereby confirming or ruling out a leading candidate explanation for the nature of dark energy.

Mots-clés : gravitational waves,tests of gravity,standard sirens
Projet ERC : SUPRABIOTICS (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Leibniz Association — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LG
Type d'entité : Recherche
Financement ERC de l'entité : 1970906.1 €

The pharmaceutical sector has a huge demand for new active compounds including natural products to fill the drug pipelines and to stop the global decline in novel approved active pharmaceutical ingredients. Therefore, developing new tools to fabricate complex molecular structures in a fast and reliable way is paramount. This holds especially true for the field of antibiotics. Multidrug resistant (MDR) pathogens evolve at a terrifying rate and confer resistance to all presently available antibacterial treatments and therefore WHO has identified MDR bacteria as major threat to human health. In this ERC Advanced Grant, I propose a radically new approach to fabricate very complex molecules with minimal synthetic effort. The technology is based on nucleic acid binders (aptamers), which are evolved in a selection protocol and block several functional groups within a target molecule while allowing other functionalities not in contact with the aptamer to be selectively modified in a single reaction step. Here, we aim to establish this groundbreaking aptameric protective group (APG) method as a novel tool that gives access to compounds that would otherwise be too difficult to obtain by multistep synthesis. Toward this end, the specific objectives are: • To develop reagents and reactions that are compatible with aptamer-mediated reactions • To control the site of chemical modification within complex molecules by APGs • To establish APGs as a general paradigm in natural product derivatization to modify several kinds of substrates • To achieve site selective modification of proteins by aptamers • To synthesize novel antibiotics that kill MDR bacteria • To fabricate “image-and-activate” antibiotics by the APG technology • To employ the aptamer-target complexes for live-cell imaging of RNA The outcomes will enable future advances in drug discovery and drug design, bioimaging technologies, and the site-specific modification of therapeutic proteins.
Projet ERC : SUPRABIOTICS (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 529093.9 €

The pharmaceutical sector has a huge demand for new active compounds including natural products to fill the drug pipelines and to stop the global decline in novel approved active pharmaceutical ingredients. Therefore, developing new tools to fabricate complex molecular structures in a fast and reliable way is paramount. This holds especially true for the field of antibiotics. Multidrug resistant (MDR) pathogens evolve at a terrifying rate and confer resistance to all presently available antibacterial treatments and therefore WHO has identified MDR bacteria as major threat to human health. In this ERC Advanced Grant, I propose a radically new approach to fabricate very complex molecules with minimal synthetic effort. The technology is based on nucleic acid binders (aptamers), which are evolved in a selection protocol and block several functional groups within a target molecule while allowing other functionalities not in contact with the aptamer to be selectively modified in a single reaction step. Here, we aim to establish this groundbreaking aptameric protective group (APG) method as a novel tool that gives access to compounds that would otherwise be too difficult to obtain by multistep synthesis. Toward this end, the specific objectives are: • To develop reagents and reactions that are compatible with aptamer-mediated reactions • To control the site of chemical modification within complex molecules by APGs • To establish APGs as a general paradigm in natural product derivatization to modify several kinds of substrates • To achieve site selective modification of proteins by aptamers • To synthesize novel antibiotics that kill MDR bacteria • To fabricate “image-and-activate” antibiotics by the APG technology • To employ the aptamer-target complexes for live-cell imaging of RNA The outcomes will enable future advances in drug discovery and drug design, bioimaging technologies, and the site-specific modification of therapeutic proteins.
Projet ERC : LeviTech (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

The phrase “no moving parts” is misleading; mechanical oscillators are the beating heart of modern technology. Whether it’s the vibration of quartz crystals setting the pace of computation, or surface acoustic wave devices amplifying signals in smartphones, mechanical oscillators are truly ubiquitous. Micro-Electromechanical Systems, or MEMS devices, dominate research into mechanical devices with technological applications. Due to their ability to be mass fabricated, they have found applications as sensors in industries ranging from healthcare to VR gaming. Their sensing performance is ultimately limited by the energy they dissipate during operation, a problem which gets worse with decreasing size. LeviTech proposes a non-obvious and inventive solution: levitation of the mechanical oscillator. By physically untethering from the environment, most energy dissipation pathways are closed, leading to ultra low-dissipation in what we term L-MEMS devices. To lay the groundwork for technological exploitation, LeviTech outlines a programme of miniaturization of both optical and electrical trapping technologies, to an intermediate state suitable for state-of-the-art sensing, generation of IP, commercial collaboration, and potential prototyping. LeviTech will deliver immediate technological application via beyond state-of-the-art pressure sensing, using a highly inventive technique whereby non-linear L-MEMS yields zero-dissipation sensing.

Mots-clés : sensing,mems sensor,optomechanics,electromechanics,miniaturization
Projet ERC : NOVOFLOP (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : KTH Royal Institute of Technology — Pays : Suède — Rôle : Partner
Acronyme de l'entité : KTH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 12500.0 €

The physical limits of CMOS scaling and the prohibitively high costs of future technology nodes, allows to foresee the end of further progress of CMOS technology in the near future and emphasizes the dire need to explore alternative technologies and computational principles. Spin as an alternative degree of freedom for computation and information storage attracts much attention due to its nonvolatility, high endurance, fast operation, and CMOS compatibility. Even though first promising results are available, these CMOS/Spintronic hybrid solutions are only competitive in comparison to conventional CMOS technology with respect to power consumption and speed - up to now - they are not able to compete in integration density. Due to the need of continuous conversion between the CMOS and the spintronic signal domain additional transistors are required, which rather leads to an integration density decrease than a densification of the circuit layout. This inspired us to avoid the signal conversion and carry out the complete device operation in the magnetic domain. The resulting non-volatile magnetic flip flop facilitates the spin transfer torque effect and magnetic exchange coupling for computation and thus enables an extremely dense layout. Instead of eight (non-clocked), twelve (clocked) or seven CMOS transistors and two magnetic tunnel junctions (CMOS/Spintronic hybrid) for a RS flip flop a footprint of only 10nmx40nm is sufficient. Furthermore, it can be stacked to a shift register which as well features a very small footprint. The device and its viability has been studied via extensive micromagnetic simulations. For the next step towards market prototypes need to be manufactured and the device performance as well as the corresponding simulation tools need to be further developed. The results of NOVOFLOP will be essential to create a package comprising prototypes, TCAD models, and a manufacturing process for presenting our device to companies and venture capitalists.

Mots-clés : flip flop,latch,spin transfer torque,sequential logic,shift register,non volatile,very large scale integration,vlsi
Projet ERC : MagTendon (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Minho — Pays : Portugal — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999854.0 €

The poor healing ability of tendons, which play a critical role in the musculoskeletal system, as well as the limitations of currently used therapies have motivated tissue engineering (TE) strategies to develop living tendon substitutes. However, the limited knowledge on tendon development and healing processes has hindered the design of TE procedures that more closely recapitulate tendon morphogenesis. Extending beyond the state-of-the-art, MagTendon will explore conventional and innovative tools such as multimaterial 3 dimensional (3D) bioprinting to design magnetic responsive systems mimicking specific aspects of tendon tissue architecture, composition and biomechanical properties, which, combined with adequate stem cells, will render appropriate behavioural instructions to stimulate the regeneration of tendon tissue. Stem cell bioengineering approaches based on superparamagnetic nanoparticles (SPMNs), namely cell sorting, mechanoreceptors targeting and cell programming, will be used to unveil the cellular signalling pathways that trigger the tenogenic differentiation of the widely and easily obtained human adipose derived stem cells. Simultaneously, the 3D cell-laden magnetic system shall enable sophisticated 3D tissue models to unravel mechanisms behind tendon homeostasis and repair that will support the base knowledge to establish rational design criteria for the biofabrication of living tendon substitutes with the adequate signaling and structural cues to recapitulate tendon tissue developmental patterns. Therefore, the ground-breaking nature of the research proposed relies on the development of disruptive technological concepts for obtaining unique cell-laden 3D magnetically responsive systems that recapitulate key features of the native tissue and that can be further remotely modulated both in vitro and in vivo by the application of external magnetic stimuli, offering the prospect of tendon regeneration as opposed to simple tissue repair.

Mots-clés : tissue engineering,tendon injury and pathology,magnetic nanoparticles,magnetic responsive materials,stem cells,tenogenic differentiation,3d bioprinting technologies,3d tissue models
Projet ERC : CapTherPV (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Universidade Nova de Lisboa — Pays : Portugal — Rôle : PI
Acronyme de l'entité : NOVA
Type d'entité : Recherche
Financement ERC de l'entité : 1999375.0 €

The possibility of having a unique device that converts thermal and photonics energy into electrical energy and simultaneously stores it, is something dreamed by the PI since the beginning of her research career. To achieve that goal, this project aims to gather, in a single substrate, solar cells with up-conversion nanoparticles, thermoelectrics and graphene super-capacitor, all made of thin films. These three main components will be developed separately and integrated sequentially. The innovation proposed is not limited to the integration of components, but rely in ground-breaking concepts: 1) thermoelectric elements based on thin film (TE-TF) oxides; 2) plasmonic nanoparticles for up conversion of near infrared radiation to visible emission in solar cells; 3) graphene super-capacitors; 4) integration and optimization of all components in a single CapTherPV device. This ambitious project will bring new insights at large area, low cost and flexible energy harvesting and comes from an old idea of combining energy conversion and storage that has been pursued by the PI. She started her career in amorphous silicon thin film solar cells, later she started the development of thin film batteries and more recently started a research line in thermoelectric films. If approved, this project will give financial support to consolidate the research being carried out and will give independence to the PI in terms of resources and creative think. More importantly, will facilitate the concretization of the dream that has been pursued with hard work.
Projet ERC : TIME-BRIDGE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Stuttgart — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 326250.0 €

The possibility to produce materials with ultra-strengths could revolutionize materials design. Since 80 years ultra-strength materials are known to exist only theoretically. Now, new experiments show that traditional believe can be overcome by nanostructured design. Yet, while selected experiments point towards this scientifically fascinating and technologically important possibility (e.g., for advances in structural and functional materials), further progress crucially relies on insight from theoretical simulations. The most successful simulation tool is molecular dynamics. Recent advances in hardware allow to tackle trillions of atoms making a comparison with nano-experiments almost possible. The nagging problem is, however, a huge time-scale gap of up to ten orders of magnitude and none of the presently available approaches is able to cope with this discrepancy. TIME-BRIDGE aims at solving the time-scale problem by borrowing a concept well known and developed in the field of first-principles simulations: the pseudopotential ansatz. In first principles simulations a similar time scale gap exists between slow and fast moving electrons. The solution is to capture the effect of the fast electrons only effectively within a pseudopotential while retaining the motion of slow electrons important for chemical bonding. An equivalent pseudopotential ansatz is envisioned to be applicable to the fast thermal motion of atoms, the origin of the time scale problem. Capturing the thermal motion in an effective potential will allow to simulate the relevant mechanical processes occurring on microsecond and second time scales. In TIME-BRIDGE high risk and high gains apply: the physics of electrons is distinct from the atomic motion possibly making the pseudopotential ansatz non-transferable, but—based on PI’s distinguished expertise and his recent methodological advancements—a route to bridge the fundamental time scale gap might arise.

Mots-clés : molecular dynamics simulations,first principles calculations,finite temperatures,method development,numerical algorithms,ultra strength,mechanical properties,computational materials design