Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CORTIGRAD (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
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 : 1110634.58 €

Historically, cognitive neuroscience has focused on discrete, mutually exclusive modules or networks, however, current network-level descriptions of brain organization fail to account for integrated features of cognition. I recently described a principal gradient in cortical connectivity that reflects how activity from primary sensory/motor areas is integrated into transmodal regions of the default-mode network. This novel line of research led me to hypothesize that coherent aspects of cognition are an emergent property of a whole brain architecture consisting of multiple zones of integration. In particular, I hypothesize that each region of transmodal cortex is the apex of a zone of integration that is anchored by multiple unimodal cortical regions. To investigate the mechanism that allows abstract representations to form in transmodal systems, I first propose structural studies to investigate covariance in zone geometry across healthy adults, how zones have emerged through evolution and how they change across the lifespan. I will then explore the functional consequence of zones of integration for higher-order human cognition. I will examine if individual differences in cognition emerges from variation in the architecture of different zones, and how brain activity is altered when simple decisions depend on integrating information from multiple zones. Finally, I will examine how the absence of input from a sensory modality (through congenital deafness or blindness) alters the structure and function of transmodal regions in a zone-specific manner. By describing how the spatial layout of the cortex shapes its functions, this research provides a radically new framework for understanding the structural constraints that underpin the integrated nature of human cognition.

Mots-clés : functional connectivity,cortical anatomy,cortical gradients
Projet ERC : TameHodge (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Humboldt-Universität zu Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1815642.0 €

Hodge theory, as developed by Deligne and Griffiths, is the main tool for analyzing the geometry and arithmetic of complex algebraic varieties, that is, solution sets of algebraic equations over the complex numbers. It occupies a central position in mathematics through its relations to differential geometry, algebraic geometry, differential equations and number theory. It is an essential fact that at heart, Hodge theory is NOT algebraic. On the other hand, some of the deepest conjectures in mathematics (the Hodge conjecture and the Grothendieck period conjecture) suggest that this transcendence is severely constrained. Recent work of myself and others suggests that tame geometry, whose idea was introduced by Grothendieck in the 1980s, is the natural setting for understanding these constraints. Tame geometry, developed by model-theorist as o-minimal geometry, has for prototype real semi-algebraic geometry, but is much richer. As a spectacular application of tame geometry, Bakker, Tsimerman and I recently reproved a famous result of Cattani-Deligne-Kaplan, often considered as the most serious evidence for the Hodge conjecture: the algebraicity of Hodge loci. I propose to lead a group at HU Berlin to explore this striking new connection between tame geometry and Hodge theory, with three axes: (I) attack the arithmetic of periods coming from the moduli space of abelian differentials; this opens a completely new perspective on this space cherished by dynamicists; (II) attack some fundamental questions for general variations of Hodge structures: fields of definition of Hodge loci (related to the conjecture that Hodge classes are absolute Hodge classes); atypical intersections, for instance for families of Calabi- Yau varieties; Ax-Schanuel conjecture for mixed period maps and for Hodge bundles; (III) attack Simpson’s « Standard conjecture » for local systems through the tame geometry of the non-abelian Hodge correspondence.

Mots-clés : hodge theory,periods,transcendence,o minimality
Projet ERC : Holo-GT (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Sapienza University of Rome — Pays : Italie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 219250.0 €

Holo-GT will define innovative ex vivo gene therapy of dominant genetic skin disease, by using Epidermolysis Bullosa (EB) as a model system. EB is a group of dominantly or recessively inherited, devastating, incurable diseases marked by structural fragility of the integuments. The applicant has shown that combined ex vivo cell and gene therapy can cure the skin of recessive LAMB3-Junctional EB. This lifesaving procedure unveiled that the human epidermis is sustained solely by long-lived stem cells, detected as holoclone-forming cells, which generate transient progenitors referred to as meroclones and paraclones. However, over 50% of EB are dominantly inherited, making gene addition unsuitable. Gene editing does not efficiently correct epidermal stem cells, which define a small proportion of clonogenic keratinocytes and cannot be prospectively isolated. Holo-GT aims at designing a safe and efficacious protocol for dominant forms of EB through: • Molecular characterization of the keratinocyte clonal types and pathways sustaining holoclone-forming cells by single-cell RNA profiling. • Generation of induced holoclone-forming cells (iHolo) by transient expression of specific sets of transcription factors (identified in aim 1) able to reprogram progenitors into holoclone-forming cells. • Development of custom-engineered CRISPR/Cas nucleases, based on selection-based directed evolution or structure-guided mutagenesis, able to fully distinguish wild type and mutant alleles. • Using this newly developed CRISPR/Cas system, gene editing of iHolo prepared from keratinocyte cultures initiated from patients with dominant forms of EB. Holo-GT could tackle not only dominant EBs but also other dominant genetic diseases of the epidermis and other squamous epithelia, as well as recessive forms of EB, particularly those characterized by the well-known depletion of stem cells, which could be rescued by the reprogramming of transient progenitors into holoclone-forming cells (iHolo).

Mots-clés : epidermal stem cells,regenerative medicine,cell therapy,gene therapy,gene editing,genetic skin diseases,epidermolysis bullosa
Projet ERC : GenGeoHol (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1300775.0 €

Holography is by now a fundamental tool in the understanding of both strongly coupled conformal field theories (CFTs) and quantum theories of gravity. While holography in Anti de Sitter (AdS) space-times is rather well understood, we currently lack a basic picture of what it means in non-AdS space-times. Considering non-AdS space-times is an essential and urgent next step in the study of quantum gravity as we seem to live in a universe with a positive cosmological constant that is approaching de Sitter (dS) in the far future. Also, the near-horizon geometries of black holes are typically described by more exotic geometries that need to be understood on their own right. I propose to address this and study the physics of holographic systems on non-AdS space-times and their connection to generalized geometric structures that naturally arise in these setups. In order do this I will use both conventional field theory techniques and new holographic tools, some of which I have developed recently. The relevance of GenGeoHol is illustrated by universal properties of black holes, e.g. their area-law entropy. These are independent of AdS, pointing towards the existence of a more general holographic principle that generalizes the usual symmetries and geometric notions. A great deal of evidence has accumulated recently indicating that this is indeed the case. The physics of extremal black holes and non relativistic systems are clear examples. GenGeoHol will impact a wide range of fields. As one moves away from AdS Einstein gravity, the dual quantum-field theories present different symmetries from that of usual relativistic systems. These systems couple naturally to generalized background geometries which are of intrinsic interest and key to a range of concepts extending from Newton-Cartan geometry in non-relativistic systems to higher-spin geometries for so-called W_N CFTs. Given my experience and track record, I am uniquely positioned to attack this problem successfully.
Projet ERC : Let-it-Bi (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1498750.0 €

Homogeneous catalysis based on transition metals has become an indispensable strategy in the development of efficient methodologies for organic synthesis, finding application in a wide variety of processes across the chemical sciences. Inspired by the wealth of reactivity in this area, we present a proposal that departs from transition metal catalysis and aims at unlocking the potential of bismuth (Bi) as a sustainable catalyst, unravelling novel and unknown catalytic redox processes for organic chemistry. The main goal of this project is to translate the unique properties traditionally associated to transition metals to a main group element. Let-it-Bi is a quest to disclose the remarkable potential of a commonly overlooked element of the periodic table such as bismuth, in the field of catalysis and organic synthesis. Being an earth abundant, non-toxic and inexpensive element, bismuth represents an excellent candidate to be explored in catalysis and to study its fundamental reactivity. In the first part of this proposal, we describe the design of a novel Bi(III)⇄Bi(V) redox cycle towards the formation of synthetically relevant and challenging C‒C, C‒Halogen, C‒N and C‒O bonds. The last part proposes the expansion of this concept to an unprecedented Bi(I)⇄Bi(III) redox cycle. Such a unique redox system will find application in the activation of small molecules (H2, NH3, B‒H and Si‒H bonds) for the functionalization of simple and largely available olefins. In addition to provide a solution to the price, toxicity and environmental issues associated to transition metal-based transformations, this proposal aims at the exploration of uncharted territories in the area of homogeneous catalysis; thus discovering and providing novel reactivities for organic synthesis which remained elusive to date. Noteworthy, preliminary results accompany both parts demonstrating the feasibility of the proposed research.
Projet ERC : EVOLHGT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : Partner
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 305124.05 €

Horizontal gene transfer (HGT) is a form of genic inheritance that occurs between individuals in a population or between species rather than from parent to offspring. HGT is most prevalent in bacteria, where it is an important source of novel metabolic pathways, pathogenicity factors, and antibiotic resistance. In spite of the importance of HGT, we understand little about the evolutionary barriers to HGT. This proposal will outline a systematic experimental approach to elucidate factors that select for or against horizontally transferred genes, by pursuing three objectives. The first is to quantify intrinsic selection acting on newly transferred genes, by experimentally transferring and expressing several hundred genes across species boundaries. We will be able to systematically classify genes as resistant or permissive to transfer, examine the effect of the function and position in metabolic and regulatory networks on resistance to transfer, as well as identify any genes with substantial intrinsic benefits. The second objective is to examine the effect of evolutionary divergence on HGT, by determining whether genes from closely related species are more permissive to transfer than those from more divergent species. The final objective is to determine the role of the environment in shaping these selective effects. Understanding how robust the selective effects are to different environmental conditions will aid in evaluating the relative roles of genetics and the environment as factors in the evolutionary outcomes of HGT . Overall, this work will provide a systematic analysis of the roles of different factors in affecting the outcomes of horizontal gene transfer. Understanding this process in a quantitative fashion is critical to understanding bacterial adaptation and diversity.

Mots-clés : horizontal gene transfer,distribution of mutational effects
Projet ERC : PHAGENET (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : National University of Ireland — Pays : Irlande — Rôle : PI
Acronyme de l'entité : NUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999988.0 €

Horizontal gene transfer (HGT) is one of the primary forces driving rapid adaptation and long term evolution of complex microbial communities such as the human microbiome. The same process is involved in the dissemination of virulence and antimicrobial resistance genes and emergence of “superbugs”. The precise mechanisms and role of HGT in the structure and function of the microbiome remain largely unexplored. Bacteriophages are ubiquitous and highly abundant members of the human microbiome, accounting for ~5% of total microbial DNA. Many of them, such as crAssphage, are highly prevalent and have evolved complex relationships with their microbial hosts. At the same time their role in microbiome composition and function is unclear. Recently we observed the accumulation of considerable amounts of bacterial genomic DNA in the phage-encapsulated fraction of human faeces (up to 50% in some instances). Analysis of this chromosomal fraction reveals that it does not appear to be due to contamination, but rather represents phage-mediated mobilisation and transfer (transduction) of DNA from specific bacterial taxa and specific genomic regions. PHAGENET argues that phage-mediated transduction plays a significant role in the genetic plasticity of the human microbiome, and that the phageome provides individual microbes with access to a wider pangenome and enables dissemination of genes both within and across individual human microbiomes. I propose to thoroughly test this hypothesis at molecular, cellular and organismal levels. This will involve an array of approaches, including long-read high-throughput sequencing, faecal chemostat models, random transposon insertion libraries in gut bacteria and animal models. By addressing an important gap in our understanding of the microbiome, PHAGENET will impact across the research areas of microbiology, virology, gastroenterology, evolutionary ecology and epidemiology.

Mots-clés : phageome,virome,bacteriophages,crassphage,horizontal gene transfer,phage transduction,mobile genetic elements,human gut microbiome,pangenome
Projet ERC : XRayProton (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Forschungsverbund Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FVB
Type d'entité : Recherche
Financement ERC de l'entité : 2482500.0 €

How acids and bases react in water is a question raised since the pioneering days of modern chemistry. Recent decades have witnessed an increased effort in elucidating the microscopic mechanisms of proton exchange between acids and bases and the important mediating role of water in this. With ultrafast spectroscopy it has been shown that the elementary steps in aqueous proton transfer occur on femtosecond to picosecond time scales. Aqueous acid-base neutralization predominantly proceeds in a sequential way via water bridging acid and base molecules. These ultrafast experiments probing molecular transitions in the ultraviolet, visible and mid-infrared spectral ranges, though, only provide limited insight into the electronic structure of acids, bases and the water molecules accommodating the transfer of protons in the condensed phase. Soft-x-ray absorption spectroscopy (XAS), probing transitions from inner-shell levels to unoccupied molecular orbitals, is a tool to monitor electronic structure with chemical element specificity. The aim is now to develop steady-state and time-resolved soft-x-ray spectroscopy of acids and bases in water-poor and water-rich solutions. Here novel liquid flatjet technology is utilized with soft-x-ray sources at synchrotrons as well as table-top laser-based high-order harmonic systems, to elucidate the electronic structural evolution of proton transfer pathways. Questions to be solved are electronic structural changes upon hydrogen bond formation, the nature of hydrated proton species, and the impact of conversion from acid to conjugate base (or base to conjugate acid) in aromatic alcohols, carboxylic and amine compounds, and ultimately the oxygen oxidation state in hydrated protons. Resolving the electronic structural dynamics of elementary steps of aqueous proton transport will furthermore elucidate the role of mediating water in bulk solution, and in specific conditions such as hydrogen fuel cells or trans-membrane proteins.
Projet ERC : OTTOCONFESSION (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Boğaziçi University — Pays : Turquie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 357950.0 €

How and why did the Ottoman Empire evolve from a fourteenth-century polity where "confessional ambiguity" between Sunnism and Shiism prevailed into an Islamic state concerned with defining and enforcing a "Sunni orthodoxy" by the early sixteenth century? Recent historiography attributes this new concern with "orthodoxy" in the Ottoman Empire to the rise of the rival Shii Safavid Empire at the turn of the sixteenth century. However, the OTTOCONFESSION project is based on the premise that the evolution of Ottoman discourse on Sunni orthodoxy can be understood only in a longer perspective that spans the fifteenth and seventeenth centuries, and that it was shaped by religio-political dynamics not only in the Safavid Empire but also within the Christian communities in the Ottoman Empire and in Europe as well. The project sets out to demonstrate that although the polarization between Sunni and Shii Islam on the one hand, and Catholic and Protestant Christianity on the other, resulted from the dynamics specific to the Turco-Iranian world and Europe, respectively, the subsequent processes of confession- (and in come cases state-) building were related and constitute an entangled history of confessionalization that spanned Europe and the Middle East. This entanglement resulted in particular from: the Ottomans' concomitant competition with the Safavids, Habsburgs, and Venetians, and the shared political theologies this entailed; the spread of various Muslim and Christian communities across imperial borders; and the Ottomans' permissiveness towards Catholic, Lutheran and Calvinist missionary activities among the Empire's (mostly Orthodox) Christians. The project will investigate the evolution of the confessional discourses in the Ottoman Empire in both community-specific and entangled, cross-communal perspectives between the fifteenth and seventeenth centuries by focusing on a) agents and strategies; b) textual genres; and c) sites of confessionalization.

Mots-clés : ottoman empire,confessionalization,social disciplining,sunnism,orthodoxy
Projet ERC : SolarALMA (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of Oslo — Pays : Norvège — Rôle : PI
Acronyme de l'entité : UiO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1995963.75 €

How are the outer layers of the Sun heated to temperatures in excess of a million kelvin? A large number of heating mechanisms have been proposed to explain this so-called coronal heating problem, one of the fundamental questions in contemporary solar physics. It is clear that the required energy is transported from the solar interior through the chromosphere into the outer layers but it remains open by which physical mechanisms and how the provided energy is eventually dissipated. The key to solving the chromospheric/coronal heating problem lies in accurate observations at high spatial, temporal and spectral resolution, facilitating the identification of the mechanisms responsible for the transport and dissipation of energy. This has so far been impeded by the small number of accessible diagnostics and the challenges with their interpretation. The interferometric Atacama Large Millimeter/submillimeter Array (ALMA) now offers impressive capabilities. Due to the properties of the solar radiation at millimeter wavelengths, ALMA serves as a linear thermometer, mapping narrow layers at different heights. It can measure the thermal structure and dynamics of the solar chromosphere and thus sources and sinks of atmospheric heating. Radio recombination and molecular lines (e.g., CO) potentially provide complementary kinetic and thermal diagnostics, while the polarisation of the continuum intensity and the Zeeman effect can be exploited for valuable chromospheric magnetic field measurements. I will develop the necessary diagnostic tools and use them for solar observations with ALMA. The preparation, optimisation and interpretation of these observations will be supported by state-of-the-art numerical simulations. A key objective is the identification of the dominant physical processes and their contributions to the transport and dissipation of energy. The results will be a major step towards solving the coronal heating problem with general implications for stellar activity.