Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : crInSitu (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Institut Pasteur — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1999780.0 €

Humans live in a symbiotic relationship with trillions of microorganisms that inhabit our bodies and play an important role in health and disease. There is a growing interest in manipulating the microbiome to improve health, yet we currently lack the knowledge and technology to carry out precise interventions. The objective of this proposal is to enable efficient in situ genetic perturbations of bacteria in the gut environment by developing the next generation of synthetic biology tools based on bacteriophage delivery vectors and CRISPR-Cas systems. The first aim is to establish a collection of genetically amenable bacteria of the human gut and the associated vectors. This will be achieved by delivering large combinatorial libraries of vectors to complex bacterial communities followed by the high-throughput identification and isolation of successfully modified bacteria. We will also identify bacterial defense systems against horizontal gene transfer and methods to bypass them. The second aim is to engineer and evolve phage vectors to deliver custom genetic circuits to the microbiome, using two main approaches: the construction of chimeric phage capsids, and the in vivo targeted mutagenesis of phage host range determinants using diversity generating retro-elements. The third aim is to perform in situ genetic perturbations in the gut environment using CRISPR-Cas tools. We will evaluate the efficiency and specificity of our phage vectors in the animal gut environment. Finally we will use our phage vectors to deliver CRISPR-Cas systems to bacteria in the mouse gut and perform forward genetic screens. This will shed light on the genetic requirements for growth in the gut and on the niche occupied by different members of the microbiome. Altogether, the knowledge and technologies developed in this project will be instrumental both to further our understanding of the gut microbiome and for the development of future microbiome targeted therapies.

Mots-clés : crispr,bacteriophage,microbiome
Projet ERC : Partres (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université norvégienne de sciences et de technologie — Pays : Norvège — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Climate change leads to increased frequency and magnitude of flash flood events in rivers and of storm surges in coastal areas. Flash floods are associated with larger discharges and water levels, whereas storm surges are characterized by higher wave heights and water levels. These events have significant consequences for both rivers and coastlines triggering a morphodynamic response. Resulting erosion and soil mechanical failures can result in severe damage to civil infrastructure and buildings. There is a knowledge gap that connects the hydraulic, hydrodynamic and geotechnical aspects of environmental loading due to current, wave action as well as sediment and soil response respectively. With the increased likelihood of extreme weather events, there is an urgent need to study coastal morphology and mitigation approaches from a multi-disciplinary physics-based perspective. Representing the interconnected processes of current, waves, sediment transport and soil deformation constitutes an interdisciplinary challenge. In the current project, particle based sediment transport models are created that take a significant step towards a realistic representation of these processes. The missing link between the individual modules will be developed, bridging the confinements of the disciplines of hydraulic, coastal and geotechnical engineering with heavy use of advanced computational fluid and solid mechanics. The multi-scale nature of extreme hydrodynamic events and their interaction with sediment and soil particle physics will be solved through a holistic multi-scale numerical framework. The proposed research lays the foundation for taking a significant step in sediment transport research that is required for dealing with current and future challenges arising from climate change. Innovative solutions to extreme weather event impact in the coastal, estuarine and riverine environments can be rapidly proposed and verified using the current numerical modeling strategy

Mots-clés : sediment transport,numerical modelling
Projet ERC : StarTicking (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Gouvernement basque — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1955875.0 €

The 24-h (circadian) timing system develops during the perinatal period and rules our physiology later in life. It has the essential task of anticipating daily recurring changes in the environment (day/night) to find the best time for each molecular and cellular process. It is organised hierarchically, with a master pacemaker in the hypothalamic suprachiasmatic nucleus (SCN), which is able to perceive environmental light and tell the body what time is it. Our modern 24/7 lifestyle favours a disruptive environment for the circadian system, which is especially negative during pregnancy. We have found, in mice and pre-term infants, that when mothers are exposed to glucocorticoids (GCs) at the wrong time of day, the offspring show behaviour disorders later in life. Our mechanistic findings showed for the first time, a role of the foetal clock before birth, challenging the view on the clock being immature and non-functional. StarTicking proposes to answer a long-standing question in the field: When and how the circadian clock starts ticking. With a multidisciplinary and integrated approach, we will go beyond the state-of-the-art to understand mechanistically the development of the central circadian pacemaker in mice and humans. We will investigate: 1) How the SCN forms by a detailed assessment of the developmental trajectory of the mouse SCN with single cell resolution. 2) When the SCN becomes functional by testing a yet unexplored player: Astrocytes as drivers of the gain of functionality of the mouse SCN. 3) What the influence of the early environment on the human SCN maturation is. The generation of a human SCN organoid will allow us to test maternal signals in vitro with high-throughput. We will link mechanistic findings to the development of SCN-driven rhythms in a cohort of pre-term babies. StarTicking will provide ground-breaking mechanistic evidence and valuable knowledge to alleviate the behavioural consequences of the circadian disruption early in life

Mots-clés : circadian clock,suprachiasmatic nuclei scn,mouse,human,development,pregnancy,early environment,premature babies,glucocorticoids,neurons,astrocytes,organoids,foetal brain,single nuclei rna seq,organotypic,per2venus,in utero electroporation,ex vivo electroporation,lineage tracing,
Projet ERC : LATIS (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Université libre de Bruxelles — Pays : Belgique — Rôle : PI
Acronyme de l'entité : ULB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1815546.0 €

The LATIS project builds on the latest advances in addressing individual atoms and engineering topological band structures in optical lattices, in view of exploring the rich physics of interacting topological matter with unprecedented control. Ultracold topological matter has recently emerged as a central theme in the realm of quantum gases. By manipulating ultracold atoms in optical lattices, various experimental groups have realized a variety of topological band structures and detected their characteristic features. Creating topological matter with ultracold atoms offers a novel view on intriguing phenomena initially discovered in the solid state but also allows for the realization of exotic states that are inaccessible in real materials. This quantum-simulation approach to topological matter generates a constructive synergy between theoretical developments driven by curiosity and concrete technological applications. Until now, ultracold topological matter has been explored in the non-interacting regime of quantum gases, so that the observed quantities are associated with single-particle states. However, exciting avenues would become accessible upon combining engineered band structures with tunable interactions. This scenario would provide a concrete path towards the experimental realization of strongly-correlated topological states in ultracold gases. A promising path to create and address such states consists in manipulating a very small ensemble of atoms within a few lattice sites of an optical lattice, as now made possible by quantum gas microscopes. This setting would allow for unprecedented control over strongly-correlated topological matter, hence offering a unique framework for many-body quantum physics. The results emanating from the LATIS project will have a substantial impact on a wide scientific community working on quantum geometry and topological states of matter, with direct consequences for ongoing experiments on synthetic topological systems.

Mots-clés : quantum simulation,optical lattices,topological states of matter,artificial gauge fields
Projet ERC : PLECTRUM (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université de Tartu — Pays : Estonie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 789189.11 €

Functional traits of organisms determine their responses to the environment, disturbances, biotic interactions, but also their effects on ecosystem processes. Therefore trait-based approaches can potentially advance our understanding of complex ecological questions. However, straightforward approaches for accurate predictions of community composition and ecosystem functioning from traits are not yet available. Studies have considered different traits, which hampers synthesis, and analytical tools have been limited. Trait-based predictions need a holistic approach incorporating all aspects of the functional structure of plant communities within a unified plant functional space (UPFS) that considers the independent information provided by above- and belowground traits. PLECTRUM takes advantage of the UPFS and provides solutions for three of the most intractable problems for trait-based ecology: (i) the dimensionality of functional variation across ecosystems, (ii) predicting functional structure from environmental variables, and (iii) using this knowledge to forecast the effects of global change on functional structure, ecosystem functioning, and species’ extinction risk. I will combine the information from massive datasets of vegetation plots and plant traits with the first global standardized sampling of key above- and belowground traits. I will use this data to quantify functional dimensionality across ecosystems, and estimate the position of thousands of species in the UPFS. Then, I will use species distributions in the UPFS analogous to images and apply deep learning methods to link the functional structure of communities to ecosystem functioning and environmental change. The methodological toolbox developed in the project, combined with the synergy of aboveground and root traits, will allow us to forecast the effects of different global change scenarios on plant communities and their functioning across scales.

Mots-clés : functional diversity,traits,global change
Projet ERC : 3D NOAM (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and Communication Engineering
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3000000.0 €

Optical frequency conversion in bulk nonlinear crystals is used for generation of coherent light over the entire optical regime from extreme ultra-violet up to THz waves. This remarkable ability is at the core of a plethora of important technological and scientific applications. However, bulk nonlinear crystals pose strong limitations on integration, miniaturization, and control over the nonlinear interactions, holding back the further progress of optical frequency conversion technologies. I propose to lead a great breakthrough in the field by developing a new kind of 3D nano-engineered nonlinear optical artificial materials with superior nonlinear optical properties, and free of the limitations of bulk nonlinear crystals. These materials will be inspired by recently developed nonlinear metasurfaces. It was demonstrated that nonlinear metasurfaces exhibit unprecedented nonlinear functionalities, and effective nonlinearities exceeding by far those of bulk nonlinear crystals, promising to replace bulk crystals in future nonlinear optical technologies. However, their two-dimensional designs and nanoscale thickness strongly limit their frequency conversion efficiency, with no existing practical nanofabrication approach nor theoretical proposition to overcome this limitation. Our research aims to close this gap. We will develop a new nanofabrication methodology that will allow to stack hundreds of nonlinear metasurfaces into a 3D nonlinear material in a technologically viable way. We will study new fundamental nonlinear interactions in these novel nonlinear materials, and demonstrate experimentally their superiority over bulk nonlinear crystals in conversion efficiency and functionalities. These achievements will potentially pave the way to the next era of nonlinear optical frequency conversion technologies. They will also immediately impact applications of 3D nanostructured optical materials in general, as well as may change the way we think about 3D nanofabrication.

Mots-clés : nonlinear metasurfaces,nonlinear optics,frequency conversion,metasurfaces,metamaterials
Projet ERC : GENESYS (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université de Tartu — Pays : Estonie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2330500.0 €

Gas fermentation provides a unique opportunity for the circular bioeconomy by enabling carbon recycling from gaseous waste feedstocks into value-added bioproducts using microbes. Acetogens are ideal biocatalysts for gas fermentation as they use gas (CO and/or CO2+H2) as their sole carbon and energy source, evidenced by the commercialisation of the waste gas-to-ethanol conversion process. Despite recent efforts, our understanding of genotype-phenotype relationships in acetogens is still minimal. This, however, is required for rational metabolic engineering and expanding the product spectrum of acetogens to unlock their full potential. GENESYS aims to engineer superior gas-fermenting cell factories through revolutionising systems-level understanding of acetogens and pioneering a new workflow for making large-scale arrayed CRISPR-engineered microbial strain libraries. First, essential genes for autotrophy of the model acetogen Clostridium autoethanogenum will be determined using a genome-wide CRISPRi screen. We then create ~750 single-gene knock-down strains of essential genes, transcription factors, and proteome “dark matter” using a novel “pooled-to-arrayed” workflow combining synthetic biology, automation, and DNA sequencing. Next, we will generate systems-level phenotype maps for up to ~750 strains through high-throughput gas fermentation and –omics analyses. Big data will be translated into a systems-level acetogen knowledgebase–A-BASE–through integrated bioinformatics and machine learning, metabolic modelling, and data engineering. Finally, we apply A-BASE to engineer acetogen cell factories from the “unexplored territories” of essential genes, transcription factors, and proteome “dark matter” for improving production of ethanol and acetone. This project will create superior gas-fermenting cell factories, advance fundamental understanding of acetogen metabolism, and pioneer a new workflow for creating large-scale arrayed engineered microbial strain libraries.

Mots-clés : acetogens,genotype phenotype relationships,gas fermentation,omics,metabolic engineering,big data analysis
Projet ERC : PassiveValueMarkers (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

When you look at a given object - are you calculating its value even if not prompted to doWhen you look at a given object - are you calculating its value even if not prompted to do so? Most theories of valuation claim that choice, prompt or in general elicitation are needed to induce valuation. However, the well-known mere exposure effect dating back to 1968, suggests that merely viewing an item can induce valuation and even enhance value. In this proposal I aim to demonstrate that valuation is an early and automatic process relying on visual, attentional and motor systems. PassiveValueMarkers offers a novel framework to identify biomarkers of value of individual items passively, without elicitation. The aims of PassiveValueMarkers are: 1) Identifying behavioural and neural passive markers for individual items using computational modelling in and influencing these markers ; 2) Detecting passive markers of value in gaze pattern analysis behaviourally and in the brain using fMRI; 3) Considering the gap that exists between laboratory studies and the real world, I will identify passive value markers in naturalistic virtual reality environments. The overreaching aim of this proposal is to develop a new theoretical framework on individual passive value construction and change. To do so, I will use a unique combination of neuroimaging, computational modelling, gaze-tracking analysis and virtual reality. This research will directly address an understudied area of how value for individual items is formed by the brain without active prompt or elicitation. Uncovering the mechanisms of passive value representation at the single item level and individualized per participant, will allow to design closed loop manipulations at the item level. This approach will serve as the basis for developing novel evidence-based methods for enhanced preference modification in healthy participants and in disorders with abnormal valuation such as addictions, mental illness, and eating disorders.

Mots-clés : value,fmri,eye gaze,virtual reality,behaviour change
Projet ERC : PIIN_T2D (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Type 2 diabetes (T2D) has reached epidemic proportions, killing millions each year; however, our incomplete understanding of its etiology hinders the quest for a cure. T2D is caused by pancreatic β-cell failure and insulin resistance. Recent studies point to aberrant islet inflammation as a driver of diabetes. While inflammation is beneficial for insulin secretion during homeostasis, it may transform to harm β-cell function and impair the glucose response. How islet inflammation maintains glucose homeostasis and why it converts to being destructive remain largely open questions. Here, I introduce a novel physiological mechanism, pericyte-orchestrated islet inflammation (PIIN), which is disturbed by diabetes risk factors to cause β-cell failure. To establish its requirement for β-cell function, we will first define the role of PIIN in homeostasis. We will then determine how T2D environmental risks, such as obesity and aging, hamper pericyte cytokine production and transform islet inflammation to cause β-cell dysfunction. Lastly, we will link T2D genetic risk factors with aberrant PIIN. To this end, we will analyze human and mouse tissues and use transgenic models to manipulate cells and genes to define the effect of PIIN on β-cell function. Ultimately, our findings will provide a mechanism through which T2D risk factors induce β-cell failure and promote disease progression. The implications of this project are far-reaching, as they will introduce a novel cellular mechanism that integrates metabolic and genetic risks to cause diabetes. Furthermore, our findings will implicate PIIN as a novel target for new therapeutic approaches to diabetes.

Mots-clés : pancreatic beta cells pericytes islet inflammation transgenic mice type 2 diabetes
Projet ERC : IMCross (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999188.0 €

Interbacterial competition is a key driver of the emergence of new bacterial strains. A widely used strategy during interbacterial competition is delivering toxins into competitors’ cytoplasm, where they target conserved components. The type VI secretion system (T6SS), a machine that delivers toxic effectors into neighboring cells, is a major player in interbacterial competitions. It fires an effector-loaded tube that penetrates the recipient cell envelope. Although many T6SS effectors target the competitors’ cytoplasm, it is not known whether they are directly deployed there or rather deployed in the periplasm and then transported into the cytoplasm. We have recently identified several domains within modular T6SS effectors that are fused specifically to cytoplasm-targeting toxic domains. The new domains are required for competitor intoxication during competition but not for T6SS-mediated secretion of the effectors. Therefore, we hypothesize that T6SS effectors are first deployed in the periplasm, where specialized domains such as these re-localize cytoplasm-targeting effectors into the recipient’s cytoplasm. In IMCross, we will leverage our unique expertise in identifying and characterizing novel domains within effectors to go beyond the state-of-the-art and determine how cytoplasm-targeting T6SS effectors reach their target. We will (1) reveal the initial site of T6SS effector deployment, (2) identify effector domains responsible for transport across the recipient inner membrane and determine whether they employ receptors in the process, and (3) establish a pipeline to discover re-localization domains and cytoplasm-targeting toxic domains in T6SS effectors. The discovery of specialized T6SS effector re-localization domains will revolutionize our understanding of effector modularity and trafficking during competition. Furthermore, such domains are key in developing tools to identify novel toxic domains and engineer synthetic toxins as alternative antibiotics.

Mots-clés : t6ss,antibacterial competition,toxin,protein secretion,membrane crossing