Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : BioNanoPattern (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
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 : 1499850.0 €

Protein nanopatterning concerns the geometric arrangement of individual proteins with nanometre accuracy. It is becoming apparent that protein nanopatterns are essential for cellular function, and have roles in cell signalling and protection, phagocytosis and stem cell differentiation. Recent research indicates that our immune system is activated by nanopatterned antibody platforms, which initiate the classical Complement pathway by binding to the first component of Complement, the C1 complex. DNA nanotechnology can be used to form self-assembled nanoscale structures, which are ideal for use as templates to pattern proteins with specific geometries and nanometre accuracy. I propose to use DNA to nanopattern antigens and agonistic aptamers with defined geometry to study and control Complement pathway activation by the C1 complex. To develop and demonstrate the potential use of DNA to nanopattern proteins, the first aim of this proposal is to design DNA nanotemplates suitable for patterning antibody-binding sites. Antibodies and C1 will bind with specific geometry, and the relationship between antibody geometry and Complement activation will be assessed using novel liposome assays. Using DNA to mimic antigenic surfaces will enable high-resolution structure determination of DNA-antibody-C1 complexes, both in solution and on lipid bilayer surfaces, using phase plate cryo-electron microscopy to elucidate the structure-activation relationship of C1. The second aim of this proposal is to evolve agonistic aptamers that directly bind to and activate C1, and incorporate these into DNA nanotemplates. These nanopatterned aptamers will enable further study of C1 activation, and allow direct targeting of Complement activation to specific cells within a population of cell types to demonstrate targeted cell killing. This may open up new and highly efficient ways to activate our immune system in vivo, with potential for targeted anti-tumour immunotherapies.

Mots-clés : dna nanotechnology,complement
Projet ERC : MolDynForSyn (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Johannes Gutenberg University Mainz — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 262339.84 €

Proteins are the building blocks of life and neurons constantly need proteins to remain functional. This is a formidable challenge because neurons must regulate dendritic protein numbers across hundreds of micrometers, and need to redistribute proteins quickly in response to any synaptic changes. For example, long-term plasticity requires new proteins. Yet, it is still a puzzle how the available pool of proteins is redistributed via diffusion or active trafficking and how synaptic protein numbers are modified by increased translation of local mRNAs. Similarly, it is now an open question how the dysregulation of mRNA transport translates into plasticity impairments, how these modify circuit functions and ultimately lead to cognitive impairments. To answer these questions and connect the molecular dynamics to circuit function, we will develop a data-driven theory describing the dendritic mRNA and protein distributions in space and time and will use it to study the emergent synaptic plasticity dynamics in dendrites and its impact on memory storage. We will use data from leading experimental labs to identify how the unique combination of dendritic mRNAs, dendritic morphology, and synaptic activity gives rise to the synaptic protein dynamics that shapes circuit function. Our theory framework will generate and test hypotheses about how individual components such as mRNA motion, translation or degradation shape the protein exchange between synapses and clarify how they translate into multi-synapse synaptic plasticity rules that give rise to memory formation, memory generalization and separation. The unique combination of theory and experimental data will improve our understanding of long-term memory mechanisms and numerous neurological diseases that are associated with neuronal trafficking pathologies or protein synthesis dysfunction.

Mots-clés : neural circuits,protein dynamics,synaptic dynamics,neural network models,computational neuroscience
Projet ERC : Protein Lego (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Bayreuth — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1928750.0 €

Proteins are ubiquitous, very diverse, and participate in virtually every cellular process. Nature has generated this impressive set of proteins using mechanisms such as recombination of smaller, sub-domain sized protein fragments that serve as building blocks in a Lego-like manner. Based on these observations we propose a rational design strategy in which new functional proteins are build from fragments of existing proteins. With this approach we aim to tackle a long-standing goal in biochemistry, namely the design of complex, custom-made proteins. Initial experiments that recombine fragments from the same as well as from different folds have been successful in creating new proteins. Moreover, the utilized fragments contribute their unique functional properties to the protein chimeras, which is a tremendous advantage of using existing subunits for the design. Here, we aim to generalize this approach. We will identify common structural fragments and classify them based on their associated functions. We will build stable hybrid proteins from different folds, transfer functional sites associated with particular fragments, and thereby learn about general design rules. The proposed approach offers a rigorous test for the identification of minimal determinants of protein structure and function. It simultaneously allows us to test our understanding of protein evolution and will have profound implications on the current view of structural classification and interactions. And lastly, the development of a reliable methodology for the design of complex proteins will be very valuable for synthetic biology and bioengineering approaches.

Mots-clés : protein design,protein engineering,molecular evolution,origin of protein domains,structural classification
Projet ERC : chemREPEAT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 1999844.0 €

Proteins hosting regions highly enriched in one or few amino acids, the so-called Low-Complexity Regions (LCR), are very common in eukaryotes and play crucial roles in biology. Homorepeats, a subfamily of LCR that present stretches of the same amino acid, perform very specialized functions facilitated by the localized enrichment of the same physicochemical property. In contrast, numerous severe pathologies have been associated to abnormally long repetitions. Despite the relevance of homorepeats, their high-resolution characterization by traditional structural biology techniques is hampered by the degeneracy of the amino acid environments and their intrinsic flexibility. In chemREPEAT, I will develop strategies to incorporate isotopically labelled and unnatural amino acids at specific positions within homorepeats that will overcome present limitations. These labelled positions will be unique probes to investigate for first time the structure and dynamics of homorepeats at atomic level using complementary biophysical techniques. Computational tools will be specifically developed to derive three-dimensional conformational ensembles of homorepeats by synergistically integrating experimental data. chemREPEAT strategies will be developed on huntingtin (Htt), the prototype of repetitive protein. Htt hosts a glutamine tract that is linked with Huntington’s disease (HD), a deadly neuropathology appearing in individuals with more than 35 consecutive Glutamine residues that represent a pathological threshold. The application of the developed approaches to several Htt constructions with different number of Glutamines will reveal the structural bases of the pathological threshold in HD and the role played by the regions flanking the Glutamine tract. The strategies designed in chemREPEAT will expand present frontiers of structural biology to unveil the structure/function relationships for LCRs. This capacity will pave the way for a rational intervention in associated diseases.

Mots-clés : protein disorder,protein dynamics,low complexity regions,huntington disease,unnatural amino acids,small angle scattering
Projet ERC : HyDegronomics (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
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 : 1801490.0 €

Proteostasis is a highly regulated process by which cells maintain a healthy proteome. Loss of proteostasis is a common feature of aging and disease. To preserve proteostasis, the cell has developed protein quality control (PQC) pathways that monitor a proteins’s fate from synthesis to degradation. Exposed hydrophobic residues in aberrant or mislocalized protein substrates is a key feature recognized by distinct PQC mechanisms. If not handled properly, exposed hydrophobicity can result in protein aggregation and subsequent reduced cell fitness. To prevent accumulation of toxic aggregates, cells are equipped both with chaperones and proteolytic pathways. Within the degradation systems, E3 ligases are the major determinants of specificity, which is achieved through their selective recognition of specific short peptide motifs, or degrons, in substrate proteins. Despite the growing list of PQC players and substrates, it has yet to be determined what are the client range, selectivity and specificity of each of the PQC mechanisms. The objective of this proposal is to systematically investigate the exposed hydrophobicity “code” and to advance the state-of-the-art of the PQC field. Here, we utilize the GPS-peptidome method that we recently developed together with genetics, biochemistry, cell biology and proteomic approaches to: (1) map distinct classes of hydrophobic degrons to elucidate the specificity of substrate selection; (2) identify novel E3 ligases playing a role in PQC pathways, explore redundancies among them and identify endogenous substrates proteome- wide; (3) investigate the physiological significance of PQC mechanisms. This work will provide a comprehensive view of PQC pathways that recognize hydrophobicity. This is critical to further our understanding on how aberrant features in proteins are recognized and can provide valuable information for the development of new therapeutic intervention strategies that target abnormal proteins implicated in disease.

Mots-clés : protein degradation,protein quality control,ubiquitination,e3 ligase,degron,hydrophobic residues
Projet ERC : FELICITY (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Institut national de recherche en sciences et technologies du numérique — Pays : France — Rôle : PI
Acronyme de l'entité : Inria
Type d'entité : Recherche
Financement ERC de l'entité : 1311687.5 €

Public key cryptography is the backbone of internet security. Yet it is very likely that within the next few decades some government or corporate entity will succeed in building a general-purpose quantum computer that is capable of breaking all of today's public key protocols. Lattice cryptography, which appears to be resilient to quantum attacks, is currently viewed as the most promising candidate to take over as the basis for cryptography in the future. Recent theoretical breakthroughs have additionally shown that lattice cryptography may even allow for constructions of primitives with novel capabilities. But even though the progress in this latter area has been considerable, the resulting schemes are still extremely impractical. The central objective of the FELICITY project is to substantially expand the boundaries of efficient lattice-based cryptography. This includes improving on the most crucial cryptographic protocols, some of which are already considered practical, as well as pushing towards efficiency in areas that currently seem out of reach. The methodology that we propose to use differs from the bulk of the research being done today. Rather than directly working on advanced primitives in which practical considerations are ignored, the focus of the project will be on finding novel ways in which to break the most fundamental barriers that are standing in the way of practicality. For this, I believe it is productive to concentrate on building schemes that stand at the frontier of what is considered efficient -- because it is there that the most critical barriers are most apparent. And since cryptographic techniques usually propagate themselves from simple to advanced primitives, improved solutions for the fundamental ones will eventually serve as building blocks for practical constructions of schemes having advanced capabilities.

Mots-clés : post quantum cryptography,lattice cryptography
Projet ERC : PyroSafe (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 2435353.0 €

PyroSafe aims at (1) creating a new generation of safe and versatile energetic materials with tailored architectures at nanoscales to replace old unsafe energetic substances currently used in pyrodevices; (2) enabling a new technology based on the co-integration of electronic components with these new types of energetic layers; (3) manufacturing high energetic microsystems able to produce multiple functionalities (gas, heat, or generation of chemical species) to implement relevant emergency safety responses. This involves both evolutionary and revolutionary advances in metal/oxide materials science and engineering that constitute the focus of the proposed work. Specifically, I will develop: i. multi-scale (nm to mm) processing methodologies combining vapor-deposition techniques with additive manufacturing methods, to tailor the structural features of the energetic layers to the application needs; ii. an understanding of the physical and chemical processes at the most fundamental level to predict composition/structure/performance relationships and aging mechanisms; iii. a heterogeneous assembly process to co-integrate the energetic layers with electronic circuits. As key achievements of the project, three safety-critical microsystems, capable of detecting catastrophes and trigger quick safety responses, will be demonstrated with prototypes, ensuring that the basic research performed in initial thrusts will directly contribute to the development of novel microsystems. Overall, the PyroSafe technology will constitute a technological breakthrough in the current “pyrotechnical systems industry” by introducing a new way of thinking and manufacturing energetic materials as safe programmable and protectable components in a field led, for decades, by organic chemistry. Furthermore, the output of this research will have a deep and broad impact on the European society by introducing a real-time response to accidents in contrast to the current approach based on prevention.

Mots-clés : nanothermites,safe and smart pyrodevices,mems,multi scale engineering
Projet ERC : QuCIP (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Tübingen — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 31462.69 €

QuCIP will deliver the first historical-critical commentary on a sizable portion of the Qur’an in English, covering the three longest and most complex compositions in the Islamic scripture, surahs 2–4, as well as the short opening surah 1. The project will thereby put forward a pioneering proof of concept for an integrative exegetical approach capable of addressing three core dimensions of the Qur’an: the compositional structure of Qur’anic texts, the intricate processes of literary growth and redactional expansion by which many of them have been shaped, and the theological concerns governing the Qur’an’s appropriation of antecedent (especially Jewish and Christian) ideas, traditions, and literary forms. Pre-modern Islamic exegesis will be critically scrutinised as a valuable repository of close scriptural reading, even if its premises and conclusions are not always persuasive to a modern historian. The result will be a paradigmatic benchmark transforming the methodological toolkit of the discipline. In realising this ambitious project, the PI will be supported by three postdoctoral scholars. Two of them will undertake foundational research into the Qur'an's compositional grammar and into Qur’anic law. The third postdoctoral researcher will support the PI’s engagement with the voluminous Islamic exegetical literature and write a reception history of surah 4. The project team will furthermore produce an edited volume or special journal issue.

Mots-clés : qur an,islam,scripture
Projet ERC : COOLER (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Potsdam — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UP
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2730184.0 €

Quantifying the feedbacks between tectonic processes in the lithosphere and climatic processes in the atmosphere is an overarching goal in Earth-Systems research, as it underpins our ability to differentiate natural from anthropogenic climate forcing. Long-term cooling during the Cenozoic has been linked to the growth of mountain belts, which enhanced erosion, chemical weathering, organic-carbon burial and drawdown of atmospheric CO2. Conversely, it has been proposed that the cooler and more variable climate of the late Cenozoic led to increased topographic relief and erosion. This latter coupling, however, has not been decisively demonstrated and remains highly controversial. Advancing our understanding of these couplings requires the development of tools that record erosion rates and relief changes with higher spatial and temporal resolution than the current state-of-the-art, and integrating the newly obtained data into next-generation numerical models that link observed erosion-rate and relief histories to potential driving mechanisms. The project COOLER shoulders this task. We will: (1) develop new high-resolution thermochronology by setting up a world-leading 4He/3He laboratory; (2) develop numerical modelling tools that incorporate the latest insights in kinetics of thermochronological systems and make sample-specific predictions; (3) couple these tools to glacial landscape-evolution models, enabling modelling of real landscapes with real thermochronology data as constraints; and (4) study potential feedbacks between glacial erosion and tectonic deformation in carefully selected field areas. The new high-resolution data will be integrated and extrapolated to quantitatively assess the impact of late Cenozoic climate change on erosion rates. Integration and analysis of the data will lead to novel insights into the two-way coupling of glacial erosion and tectonics, as well as latitudinal trends in glacial erosion patterns.

Mots-clés : thermochronology,cenozoic climate change,erosion,numerical modelling
Projet ERC : QCDHighDensityCMS (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Sapienza University of Rome — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1281246.0 €

Quantum Chromodynamics (QCD) is the theory of the strong force. Its high-temperature phase can be accessed experimentally via high energy heavy-ion collisions, allowing us to investigate how the macroscopic properties of nuclear matter arise from QCD interactions between quarks and gluons. With this proposal I aim to solve several fundamental and long-standing questions concerning the strong force and the evolution of the high density phase of QCD, the Quark Gluon plasma (QGP), that are related to the evolution of the early universe: a) Characterize the transport coefficient, qhat, of the Quark Gluon Plasma, which is related to its density b) Perform the equivalent of the Rutherford experiment in the QGP, to resolve the point-like quark and gluon scatterers within the QGP. c) Provide first experimental evidence of two important interference mechanisms that are expected to play a main role in the evolution of jets in a QGP, such as the Landau Pomeranchuk Migdal effect in QCD and the color coherence effect d) Study the phenomenology of the Lund plane, in particular selections on the branching time obtained from the splitting kinematics. Can it be used to draw a time-dependent picture of the jet shower? e)Perform the first attempt to time-scan the QGP with a yoctosecond chronometer using hadronic decays of W and Z bosons. As a world leader in the field of jet physics, also with a strong phenomenological background, I am in a unique position to to solve some of the most interesting problems concerning QCD at high densities by applying new ideas and techniques and exploring the jet substructure. The CMS detector capabilities for jet and electroweak boson reconstruction and the synergy between the pp and heavy ion communities within, make of CMS the ideal experimental detector to capitalize on my ideas and existing expertise. This grant will also provide the opportunity to reinforce the european contribution to the CMS heavy ion program and lead it.

Mots-clés : jet physics,jet quenching