Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MicroMOUPE (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Vienna — Pays : Autriche — Rôle : PI
Acronyme de l'entité : Univie
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1672752.0 €

The sensitivity of modern microscopy is limited by shot-noise. It limits the accuracy of measurements of specimen properties as well as the spatial resolution of electron microscopes when imaging sensitive specimens, such as proteins or DNA. But the shot-noise limit is not a fundamental limit. A technologically feasible and optimal approach to overcoming the shot-noise limit is to have each probe particle interact with the specimen multiple times. We recently introduced this concept to microscopy using self-imaging cavities. Within this project, I want to demonstrate post-selection free sub-shot noise microscopy with both photons and electrons. Optically this will be possible by introducing a fast electro-optical switch into a multi-pass microscope, evading the need for temporal post-selection. After this proof-of principle experiment, the sensitivity enhancement offered by multi-pass microscopy shall be applied to the detection of nanometric particles, such as single molecules, proteins and metal nanoparticles. Linear signal enhancement with the number of interactions is expected for bright-field microscopy. For dark-field microscopy a quadratic enhancement is expected, due to coherent build-up of scattered fields. Finally, adaptive optics will be used to optimize multi-pass microscopy for the study of cells. Multi-pass electron microscopy will be realized in collaboration with Stanford University. It will require several novel electron optical elements that will be designed and tested both at Stanford University and at the University of Vienna. One of these elements will be a pattern generator for electrons based on ponderomotive potentials. The required potential landscapes will be created using adaptive optics to shape intense laser pulses. With this novel electron optics tool fast beam-blanking, a phase plate for Zernike phase microscopy, arbitrary pattern creation and aberration correction will be demonstrated.

Mots-clés : high sensitivity,low damage microscopy,sub shot noise measurements,electron optics,electron light interaction
Projet ERC : CRISS (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Bar-Ilan University — Pays : Israël — Rôle : PI
Acronyme de l'entité : BIU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1372839.0 €

The severe combined immunodeficiencies (SCIDs) are a set of life threatening genetic diseases in which patients are born with mutations in single genes and are unable to develop functional immune systems. While allogeneic bone marrow transplantation can be curative for these diseases, there remain significant limitations to this approach. Gene therapy using viral vectors containing a corrective transgene is being developed for some of these disorders, most successfully for ADA-SCID. However, for other SCID disorders, such as those caused by genetic mutations in RAG1 and RAG2, the transgene needs to be expressed in a precise, developmental and lineage specific manner to achieve functional gene correction and to avoid the risks of cellular transformation. In contrast to using viral vectors to deliver transgenes in an uncontrolled fashion, we are working towards using genome editing by homologous recombination (HR) to correct the disease causing mutation by precisely modifying the genome. We have shown that by using clustered, regularly interspaced, short palindromic repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9) system we can stimulate genome editing by HR at frequencies that should be therapeutically beneficial (>10%) in hematopoietic stem and progenitor cells (HSPCs). The overall focus of the proposal is to translate our basic science studies to use in RAG-SCID patient-derived HSPCs in methodical, careful and pre-clinically relevant fashion. The fundamental approach is to develop a highly active functional genome editing system using CRISPR-Cas9 for RAG-SCIDs and complete pre-clinical efficacy and safety studies to show the approach has a clear path towards future clinical trials. Our goal with this proposal is to develop the next wave of curative therapies for SCIDs and other hematopoietic disorders using genome editing.

Mots-clés : genome editing,crispr,precision medicine,homologous recombination,dna repair,severe combined immunodeficiency
Projet ERC : FunCapSys (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2478236.0 €

The simplest living organism is composed of myriad chemical subsystems, each consisting of structurally complex biomolecules that interact in many ways; the properties of life emerge from these dense connections. Understanding how these interactions take place will help elucidate the foundations of biology, as well as enabling the design and creation of new chemical networks with targeted functions. Deciphering and designing chemical systems requires new tools to be developed, however. In this research programme, we will develop new means for engineering functional chemical systems based upon the use of guest-binding capsules. These hosts will respond to many different signals in predictable ways. Their responses will enable their guests to be transformed in new ways or pumped between phases using light. Chemical signals will enable hosts to be transformed reversibly or irreversibly, changing their guest binding properties so as to favour some guests and disfavour others, and catalysts will be released or taken up, accelerating or impeding catalysed transformations. Ultimately we will design systems where signal transduction occurs in complex cycles and feedback loops, allowing complex behaviour to emerge from abiological systems.

Mots-clés : host guest chemistry,encapsulation,catalysis
Projet ERC : CHANGE (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
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 : 810471.24 €

The simulation of Partial Differential Equations (PDEs) is an indispensable tool for innovation in science and technology. Computer-based simulation of PDEs approximates unknowns defined on a geometrical entity such as the computational domain with all of its properties. Mainly due to historical reasons, geometric design and numerical methods for PDEs have been developed independently, resulting in tools that rely on different representations of the same objects. CHANGE aims at developing innovative mathematical tools for numerically solving PDEs and for geometric modeling and processing, the final goal being the definition of a common framework where geometrical entities and simulation are coherently integrated and where adaptive methods can be used to guarantee optimal use of computer resources, from the geometric description to the simulation. We will concentrate on two classes of methods for the discretisation of PDEs that are having growing impact: isogeometric methods and variational methods on polyhedral partitions. They are both extensions of standard finite elements enjoying exciting features, but both lack of an ad-hoc geometric modelling counterpart. We will extend numerical methods to ensure robustness on the most general geometric models, and we will develop geometric tools to construct, manipulate and refine such models. Based on our tools, we will design an innovative adaptive framework, that jointly exploits multilevel representation of geometric entities and PDE unknowns. Moreover, efficient algorithms call for efficient implementation: the issue of the optimisation of our algorithms on modern computer architecture will be addressed. Our research (and the team involved in the project) will combine competencies in computer science, numerical analysis, high performance computing, and computational mechanics. Leveraging our innovative tools, we will also tackle challenging numerical problems deriving from bio-mechanical applications.

Mots-clés : numerical methods for pdes,isogeometric methods,numerical methods on polyhedral meshes,geometric modeling and processing
Projet ERC : CIRCADYN (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
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 : 1999963.0 €

The skin is the largest organ of the body and represents the primary physical barrier to the environment. Circadian, ~24h rhythms in the environment have emerged as important regulators of the immune system, yet, the circadian dynamics of leukocyte turnover and function in the skin are completely unknown. Insights into the mechanisms occurring at this host-environment interface will be of key importance to understand how rhythmicity in the immune system is achieved. This will produce knowledge to optimize adjuvant design and maximize adaptive immune responses such as required in vaccinations, ultimately providing a time window for therapy. We will elucidate how circadian dynamics in leukocyte input and output to the skin interplay to create oscillatory numbers of leukocytes in this tissue. We will assess the impact of lineage-specific rhythmicity and arrhythmicity on skin immune homeostasis using an innovative combination of novel genetic tools. We will mechanistically assess how circadian leukocyte dynamics in the skin are governed at a higher level by the sympathetic nervous system. We will finally unravel the cause and the functional relevance of circadian leukocyte dynamics in the skin by assessing whether they primarily represent a response to exogenous factors or whether they are caused by physiological tissue turnover in response to daily recurring mechanical stress. Based on these data we will create a mathematical model determining circadian skin leukocyte turnover in a quantitative manner. The project combines the disciplines of immunology and chronobiology by obtaining unprecedented insights into circadian immunity in the skin, a critical epithelial barrier site, which is of broad impact for both fields. Our extensive experience in the rhythmic control of both the innate and adaptive immune system makes us well poised to unravel the molecular mechanisms that orchestrate circadian leukocyte dynamics in the skin.

Mots-clés : circadian rhythms,leukocyte migration,leukocyte turnover,skin
Projet ERC : DDRNA (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : FIRC Institute of Molecular Oncology — Pays : Italie — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 111000.0 €

The so-called “DNA damage response” (DDR) is a coordinated set of evolutionary-conserved events that, triggered upon DNA damage detection, arrests the cell-cycle and attempts DNA repair. Recently, we have unveiled and reported that DDR activation depends on RNA. We observed that DNA double-strand breaks (DSBs) trigger the local generation of small non-coding RNAs at the site of DNA damage carrying the sequence surrounding the damaged site. These DDR RNAs (DDRNAs) are essential for DDR activation: removal of DDRNAs by RNAse A treatment of permeabilized cells inhibits DDR activation and DDR can be fully restored by the addition of chemically-synthesized DDRNA carrying the sequence surrounding the damaged site but not other sequences (Francia, Nature 2012). Cancer cells must preserve unlimited proliferative potential. We have previously shown that oncogene activation (and therefore cell transformation) is associated with DDR activation at fragile sites (Di Micco, Nature 2006). Several studies have shown that RNA functions can be inhibited by antisense oligonucleotides (ASO) that act by pairing with target RNAs. We propose scientific development and commercialization activities to bring to a clinical application a therapeutic approach for tumors based on DDRNA inhibition by ASO. Analysis of prior art indicate that there is no overlapping IP protection. Based on our solid IPR, we trust we have an excellent candidate for a first-in-class tool to block proliferation in a subtype of tumors.

Mots-clés : dna damage response  ddr,non coding rna,dna damage response rna  ddrna,cancer
Projet ERC : BOSS-WAVES (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Acronyme de l'entité : KUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1991959.76 €

The solar coronal heating problem is a long-standing astrophysical problem. The slow DC (reconnection) heating models are well developed in detailed 3D numerical simulations. The fast AC (wave) heating mechanisms have traditionally been neglected since there were no wave observations. Since 2007, we know that the solar atmosphere is filled with transverse waves, but still we have no adequate models (except for my own 1D analytical models) for their dissipation and plasma heating by these waves. We urgently need to know the contribution of these waves to the coronal heating problem. In BOSS-WAVES, I will innovate the AC wave heating models by utilising novel 3D numerical simulations of propagating transverse waves. From previous results in my team, I know that the inclusion of the back-reaction of the solar plasma is crucial in understanding the energy dissipation: the wave heating leads to chromospheric evaporation and plasma mixing (by the Kelvin-Helmholtz instability). BOSS-WAVES will bring the AC heating models to the same level of state-of-the-art DC heating models. The high-risk, high-gain goals are (1) to create a coronal loop heated by waves, starting from an "empty" corona, by evaporating chromospheric material, and (2) to pioneer models for whole active regions heated by transverse waves.

Mots-clés : solar corona,coronal heating,3d simulations,transverse waves
Projet ERC : DEEPTIME (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
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 : 2495496.0 €

The solar system represents the archetype for the formation of rocky planets and habitable worlds. A full understanding of its formation and earliest evolution is thus one of the most fundamental goals in natural sciences. The only tangible record of the formative stages of the solar system comes from ancient meteorites and their components some of which date back to the to the birth of our Sun. The main objective of this proposal is to investigate the timescales and processes leading to the formation of the solar system, including the delivery of volatile elements to the accretion regions of rocky planets, by combining absolute ages, isotopic and trace element compositions as well as atomic and structural analysis of meteorites and their components. We identify nucleosynthetic fingerprinting as a tool allowing us to probe the history of solids parental to our solar system across cosmic times, namely from their parent stars in the Galaxy through their modification and incorporation into disk objects, including asteroidal bodies and planets. Our data will be obtained using state-of-the-art instruments including mass-spectrometers (MC-ICPMS, TIMS, SIMS), atom probe and transmission electron microscopy. These data will allow us to: (1) provide formation timescales for presolar grains and their parent stars as well as understand how these grains may control the solar system’s nucleosynthetic variability, (2) track the formation timescales of disk reservoirs and the mass fluxes between and within these regions (3) better our understanding of the timing and flux of volatile elements to the inner protoplanetary disk as well as the timescales and mechanism of primordial crust formation in rocky planets. The novel questions outlined in this proposal, including high-risk high-gain ventures, can only now be tackled using pioneering methods and approaches developed by the PI’s group and collaborators. Thus, we are in a unique position to make step-change discoveries.

Mots-clés : solar system formation,meteorites,isotopes,chronology,nucleosynthesis,planet formation
Projet ERC : TeloHOOK (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
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 : 1795010.0 €

The spatial and temporal organization of the nucleus and its components are essential for genome regulation. During interphase of mammalian cells the nuclear envelope maintains the shape and the mechanical integrity of the nucleus, but also provides an anchor for chromatin that is connected to its inner side. This interaction mediates the regulation of gene expression, DNA replication and the maintenance of genome stability. In human cells I found that a large subset of telomeres, the natural ends of linear chromosomes, are transiently anchored to the nuclear envelope specifically during postmitotic nuclear assembly. Chromatin organization undergoes extensive changes during progression through the cell cycle, particularly during mitosis with the nuclear envelope breakdown and the compaction of chromatin into metaphase chromosomes. The interaction between chromosome ends and the nuclear envelope at the stage where the nucleus is reforming post-mitosis suggests a new role for telomeres in nuclear organization. My aims are 1) to screen for interacting partners that mediate the cell-cycle dependent telomere tethering to the nuclear membrane; 2) to unravel the molecular mechanism of telomere-nuclear envelope association over the cell cycle by combining biochemistry and state-of-the-art microscopy; 3) to map the subset of chromosomes which ends are tethered using subtelomere specific FISH probes and determine whether they are conserved throughout cell divisions and if it plays a role in organizing chromosome territories; 4) to examine telomere dynamics in cells from premature aging syndromes affecting the nuclear envelope integrity using live imaging confocal microscopy, and understand the connection between telomeres, nuclear envelope, and aging. The originality of my scientific approach is to combine state-of-the-art cell biology, biochemistry, and molecular biology for an integrated view of human telomere function in nuclear organization.

Mots-clés : telomeres,genome organization,nuclear envelope,aging,dynamics
Projet ERC : SCIFY (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Acronyme de l'entité : KUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2270202.0 €

The spectral characterisation and understanding of terrestrial exoplanets is currently one of the most ambitious and challenging long-term goals of astrophysics. All observing techniques with the potential to tackle this challenge face the same limitations: the overwhelmingly dominant flux of the host star and/or the lack of angular resolution. A very promising technical solution around these issues is nulling interferometry, which combines the advantages of stellar interferometry (high angular resolution) and coronagraphy (starlight rejection). For several years, we have been developing both data acquisition and data processing techniques based on self-calibration of the interferometric observable and demonstrated record-breaking starlight rejection on two American ground-based facilities. With the SCIFY project, I propose to prototype the first nulling interferometric instrument for the European Very Large Telescope Interferometer. By leveraging its state-of-the-art infrastructure, long baselines, and strategic position in the Southern hemisphere, the new VLTI instrument will be able to carry out several high-impact exoplanet programmes to characterise the chemical composition of Jupiter-like exoplanets at the most relevant angular separations (i.e., close to the snow line) and better understand how planets form and evolve. To achieve these goals, we will demonstrate a new observing technique called spectral self-calibration, combining nulling interferometry with high-dispersion spectroscopy, and adapt our advanced post-processing techniques to the VLTI. This will provide a new and more robust open-source general-purpose interferometric data reduction tool to the VLTI community. In the long term, the SCIFY project will be a cornerstone in the roadmap leading to the characterisation of terrestrial exoplanets and the search for life beyond Earth.

Mots-clés : exoplanets,exozodiacal disks,interferometry,nulling interferometry,opd control,integrated optics,vlti
Projet ERC : SCIFY (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of Liège — Pays : Belgique — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 160000.0 €

The spectral characterisation and understanding of terrestrial exoplanets is currently one of the most ambitious and challenging long-term goals of astrophysics. All observing techniques with the potential to tackle this challenge face the same limitations: the overwhelmingly dominant flux of the host star and/or the lack of angular resolution. A very promising technical solution around these issues is nulling interferometry, which combines the advantages of stellar interferometry (high angular resolution) and coronagraphy (starlight rejection). For several years, we have been developing both data acquisition and data processing techniques based on self-calibration of the interferometric observable and demonstrated record-breaking starlight rejection on two American ground-based facilities. With the SCIFY project, I propose to prototype the first nulling interferometric instrument for the European Very Large Telescope Interferometer. By leveraging its state-of-the-art infrastructure, long baselines, and strategic position in the Southern hemisphere, the new VLTI instrument will be able to carry out several high-impact exoplanet programmes to characterise the chemical composition of Jupiter-like exoplanets at the most relevant angular separations (i.e., close to the snow line) and better understand how planets form and evolve. To achieve these goals, we will demonstrate a new observing technique called spectral self-calibration, combining nulling interferometry with high-dispersion spectroscopy, and adapt our advanced post-processing techniques to the VLTI. This will provide a new and more robust open-source general-purpose interferometric data reduction tool to the VLTI community. In the long term, the SCIFY project will be a cornerstone in the roadmap leading to the characterisation of terrestrial exoplanets and the search for life beyond Earth.

Mots-clés : exoplanets,exozodiacal disks,interferometry,nulling interferometry,opd control,integrated optics,vlti