Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Custom-Made (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université technique du Danemark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : DTU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

The rising incidence of age-associated neurodegenerative diseases, due to increased life expectancy, poses a challenge to the brain's limited regenerative capabilities. Stem cell-based therapies offer promise for addressing crucial neuron loss, particularly in Parkinson’s and Huntington’s diseases (PD and HD). Ongoing first-generation stem cell trials, replacing damaged neurons with healthy ones, represent a notable advancement. However, their impact is constrained by a ‘one-cell-fits-all’ generic therapy that does not take in account the diverse clinical needs due to variations in disease etiology, stage, patient heterogeneity, and daily fluctuations in graft requirements. CUSTOM-MADE is a transformative initiative advancing knowledge and crafting a tailored portfolio of stem cell products for individual patients or patient subgroups, notably targeting PD and HD. Integrating stem cell technologies, genomics and bioengineering, CUSTOM-MADE develops rational graft composites of therapeutic neurons and complementary cells to meet the clinical needs of individual patients. Moving into preclinical animal models, the project refines graft connectivity and functional recovery post-transplantation. A groundbreaking leap involves modeling circuitry reconstruction in a fully humanized 3D in-vitro bioengineered system - the connectoids, allowing detailed studies at cellular and molecular levels for defining factors controlling correct and functional graft integration. For increased translatability, CUSTOM-MADE pioneers the generation of cell products whose activity can be self-regulated or tuned to the patients’ individual requirements. The project implements strategic measures to shield grafts from pathology and introduces the innovative concept of grafted cells exhibiting disease-modifying activity. In essence, CUSTOM-MADE drives the field toward customized stem-cell therapies for PD and HD, marking a paradigm shift in the treatment landscape of neurodegenerative diseases.

Mots-clés : connectoids,biosensors,chemogenetics,activity regulators,parkinson s disease,huntington s disease
Projet ERC : TalkingPhages (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : CO-PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2835000.0 €

Communication between organisms is one of the most sophisticated forms of social interactions. It has been recently discovered that bacterial viruses (phages) show multiple social attributes including the ability to communicate extracellularly with their progenies through a peptide-based system called arbitrium. This system is utilized by phages to guide life-cycle decisions, such as the transitions between their quiescence and virulence states. It has subsequently become clear that this system is not exclusive to phages but is also present in other mobile genetic elements (MGEs) and that its underlying design and function has diversified considerably. Despite the wide-ranging impact of these discoveries, the molecular basis of these new systems of communication, and their function in different MGEs, remain to be deciphered. More importantly, although it has been proposed that phages only communicate with their progeny, our preliminary results indicate that the arbitrium system can be used by phages and other elements to communicate with unrelated MGEs, sometimes present in different bacterial species. However, the prevalence and ecological role of this unprecedented inter-MGE communication is unclear. In the TalkingPhages project, we’ll explore all these questions and establish the molecular basis used by arbitrium systems to shape MGE diversity, interactions amongst MGEs and bacterial ecology and evolution. Our team combines expertise in MGEs and communication systems using tools from genetics (Penadés), biochemistry (Marina) and eco-evolutionary dynamics (Eldar). By exposing the multi-layered network of communications between MGEs, which is amenable for exploration on multiple levels of resolution, this project would set a milestone in understanding the complex eco-evolutionary dynamics of MGEs and the relevance of their sociality, with potential impact on our understanding of virulence and resistance in clinically and agriculturally important bacterial species.

Mots-clés : bacteria,phages,mobile genetic elements,quorum sensing,communication,evolution,ecology,molecular biology,bacillus,arbitrium,cooperation
Projet ERC : Cat4CanCenter (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Antoni van Leeuwenhoekziekenhuis — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : AVL
Type d'entité : Recherche
Financement ERC de l'entité : 3557800.0 €

The increased incidence and mortality of tumors that do not respond to standard of care or other targeted therapies is a major challenge in clinical management of these cancer patients. In order to provide innovative therapeutic avenues for treatment refractory patients, it is urgent to develop novel mechanisms of anticancer drugs mode of action that will overcome the drawbacks of current therapies. In Cat4CanCenter, we will merge the research fields of metal-based catalysis for drug development and innovative delivery routes with cancer biology and immunology, applied to one of the deadliest cancers, glioblastoma (GBM), a fatal primary brain tumor for which no curing therapy exists, due to its location within the brain parenchyma and complex tumor microenvironment. Many potential drugs failed in the clinic due to their inherent toxicity and off-target side-effects, which add up to the challenges in reaching the protected brain site. Recently, innovative catalyst design enabled synthetic transformations in the presence of biological molecules. In Cat4CanCenter we will develop four innovative approaches to treat GBM. This new methodology requires the design of cage protected catalysts that will be delivered to targeted cell types using advanced lipid nanoparticle technology. Next, the catalysts will convert nontoxic prodrugs into active drugs within the GBM bulk. Our groundbreaking strategy aims for successful therapies to treat glioblastoma, by developing complementary approaches to therapeutically tackle the complexity of this disease. The new strategies, catalysts and prodrIn this project we explore a new avenue to treat glioblastoma, which is the most difficult cancer to target. In a collaborative program we develop biomimetic transition metal catalysts (key expertise 1) that will be delivered using smart strategies such as lipid nanoparticles (key expertise 2) to generate cancer drug in vivo. The glioblastoma biology will be studies in detail (key expertise 3).

Mots-clés : supramolecular cage catalysis transition metal catalysis glioblastoma tumor micro environment
Projet ERC : Horsepower (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : CO-PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 3265300.0 €

Horse Power will examine the complex interactions between the eastern steppe and China from the second millennium BCE to the formation of the Xiongnu empire in Mongolia and the Qin state in China after 300 BCE. From the second millennium BCE two great worlds formed, traded and fought across Eurasia. From Mongolia to the European steppe great horse and herding cultures coalesced across thousands of kilometres of grassland. To the south, a string of states existed from Egypt to the Chinese Central Plains, some already ancient and others newly created. Interaction between these worlds was constant and profoundly formative for all parties, a fact we are only starting to fully appreciate. To examine the connections between the steppe, Mongolia and China’s Central Plains we will combine the latest scientific techniques in genetics and metallurgical analysis with theory concerning politics and power within and between China and its northern neighbours. Three principal empirical elements underpin the project: ancient DNA from horses; the characterization of bronzes to throw light on their movement and recycling; the structure and contents of archaeological sites (mainly graves) in China, Mongolia and the steppe. We will develop theory on the nature of leadership and power, particularly in mobile societies. Science will meet social science in a mutually informative manner and we will work across linguistic boundaries (Chinese, Mongolian, Russian, English) in a spirit of the co-production of knowledge with important partners including The Emperor Qin Shihuang’s Mausoleum Site Museum in China and Mongolian universities. We will reflect on our working practices, engaging a broader public in how a complex research project works. An innovative artistic programme will engage a range of local communities, horse enthusiasts and local artists in the work and results of the project. Working together we will create a picture of this complex region impossible if we had worked alone.

Mots-clés : cosmology,horse genetics
Projet ERC : REAL (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de Lausanne — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3400029.0 €

How can we sustain human well-being within planetary boundaries? What policies and provisioning systems could enable societies to prosper without growth? What politics and alliances are necessary for seeing post-growth policies through, and how can the public be engaged in them? What new scientific paradigm could answer such questions?  Societies face multiple intertwined crises. Bold alternatives are sorely needed. This project develops frameworks for ‘Post-Growth Deals’, from empirical research through to practical applications. First, we develop equitable North-South convergence scenarios, modelling human well-being achievement in all countries within planetary boundaries. Second, we articulate post-growth policy packages for the Global North and South, assessing their political acceptability and modelling their effects. Third, we develop models of provisioning systems to ensure future populations have adequate energy, food, shelter, health and social security. Fourth, we learn from political movements, studying politics and alliances that could bring post-growth transitions forward. Fifth, we identify practical steps to bring Post-Growth Deals to life, working with four representative communities to co-produce knowledge and action on the ground.  The potential gains of this research are immense: post-growth transitions may unlock a far more ecologically stable and socially prosperous future than current trajectories lead to. REAL brings a paradigm shift moving post-growth science from economics to sustainability studies. We propose a new trans-disciplinary ‘5Ps of post-growth’ science, grounded in resource/energy modelling, political-economy and socio-political analysis – a skill-set that no single researcher or team presently possesses. The PIs are leaders in their fields and bring complementary expertise in: modelling of provisioning systems (JST), political economy and North-South relations (JΗ), and the politics of socio-environmental transformations (GK).

Mots-clés : limits to growth,post growth,degrowth,ecological economics,political ecology,industrial ecology,unequal exchange,environmental justice,climate justice,provisioning systems,planetary boundaries,wellbeing
Projet ERC : Archean Park (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université de Duisbourg et Essen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2560425.0 €

The biological conversion of inorganic to organic carbon, autotrophic CO2 fixation, is arguably the most important biosynthetic process on Earth. Having been established early in the Archean Eon, a period characterized by an atmosphere rich in CO2, this metabolism helped spark and fuel the evolution of early microbial life. Mounting evidence suggests that exceedingly high levels of CO2 select for energetically efficient CO2 fixation pathways, immensely affecting carbon cycling. We hypothesize that CO2-rich subsurface ecosystems still harbor microbes that prefer or even require extremely high CO2 concentrations; we refer to these microbes as carbodioxyphiles. Accordingly, elevated CO2 levels would impact the thermodynamics of the microbial central carbon metabolism, enhancing autotrophy and hindering remineralization of organic matter by heterotrophs. To this end, we will study microbial life in CO2-rich subsurface environments and elucidate ancient metabolic pathways rendered obsolete by the CO2 levels of most modern environments. Each of the research team’s members has contributed to prior breakthroughs in novel autotrophic pathways, environmental genomics, metabolomics, and/or the biogeochemistry of deep subsurface environments. Establishing optimal synergy in this wealth of expertise and experience, we will describe novel modes of microbial carbon fixation in CO2-rich settings and elucidate the importance of carbodioxyphily for microbial evolution. Archean Park will provide a unique window through which to study a new mode of cellular biochemistry, the relicts of primordial carbon fixation, and Earth’s earliest carbon cycle. We will comprehensively characterize the metabolic mechanisms exploited by microbes to achieve evolutionary dominion in these relict environments. Our findings will stimulate biotechnological and geotechnical innovations ranging from enhanced autotrophic biomass production to improved carbon sequestration and storage.

Mots-clés : autotrophy,metabolism,carbon cycle,deep biosphere,microbial physiology
Projet ERC : NEMESIS (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Hospital Clínic de Barcelona — Pays : Espagne — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 56250.0 €

Focal brain disorders, including stroke, trauma, and epilepsy, are the main causes of disability and loss of productivity in the world, and carry a cumulative cost in Europe of about 500 billion euro/year. Now, physicians diagnose and treat these conditions as if they were caused by local dysfunction due to the pathological process. However, there is growing evidence that, in most neurological and psychiatric disorders, clinical symptoms reflect widespread network abnormalities. Normalization of such network abnormalities through “circuit-based” stimulation would therefore improve function. However, this form of therapy is currently limited by numerous factors: lack of knowledge about the underlying mechanisms and their behavioural relevance; inability to map these abnormalities onto single patients; and, most importantly, a principled understanding of where and how to stimulate the brain to produce functional recovery. ‘NEMESIS’, from Ancient Greek as “give what is due”, aims to “give an injured brain what is missing”, i.e., restore through stimulation normal activity in dysfunctional brain circuitries. By synergizing people, concepts, and technologies, NEMESIS will first characterize the effects of focal injury at multiple spatial and temporal scales (from whole brain to local circuits). Through the combination of observational (e.g., fMRI, EEG, calcium imaging, LFPs) and causal methods (e.g., electro-magnetic stimulation, optogenetics) NEMESIS will test the hypothesis that disconnected networks lie in a “sleep-like state” that impairs communication. Thirdly, NEMESIS will create whole brain models of structure/function to predict the effect of individual lesions and simulate novel stimulation protocols aimed at “re-awakening” the disconnected brain. Finally, proof-of-concept interventions that combine circuit-based stimulation and behavioural training, guided by modelling and animal studies, will be tested to restore normal activity, and so give back what is due.

Mots-clés : focal injury,brain networks,brain rhythms,sleep,slow wave oscillations,whole brain computational models,brain stimulation,brain connectivity,fmri,eeg,lfp,calcium imaging,tms,7t mri
Projet ERC : RECLESS (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Vienne — Pays : Autriche — Rôle : PI
Acronyme de l'entité : Uni Wien
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2509002.0 €

RECLESS will predict how ongoing ocean deoxygenation impacts microbial nitrogen transformations and thereby the future availability of nitrogen to support oceanic primary production and carbon sequestration. Microbial conversions of bioavailable nitrogen to dinitrogen in oxygen-depleted waters currently account for ~30% of the marine nitrogen loss, despite oxygen-depleted waters making up just 0.1% of the ocean volume. Models predict accelerating expansion of oxygen depletion, which entails increased nitrogen loss with negative impacts on ecosystem function and oceanic carbon sequestration, as well as an associated production of greenhouse-forcing nitrous oxide. However, biogeochemical ocean models currently fail to reproduce fundamental aspects of the microbial nitrogen transformations observed experimentally, including how nitrogen is either recycled or lost in oxygen-depleted waters. This reflects fundamental knowledge gaps concerning the environmental controls on growth, mortality, and activity of microbial populations, which preclude robust model predictions. RECLESS breaks new ground by synergistically integrating innovative oceanographic, biogeochemical, ecophysiological, and model-based investigations to close these gaps. With unprecedented in situ ecophysiological experiments using novel custom-made instrumentation as a cornerstone, RECLESS will identify key organisms, quantify their response to environmental controls, and construct the first comprehensive global microbial ecosystem model for oxygen-depleted marine systems. This model will enable robust predictions of how ocean deoxygenation affects nitrogen cycling and loss, greenhouse gas production, and interactions with the carbon cycle. Thus, RECLESS will transform our understanding of the present and future marine nitrogen cycle and its climate interactions, and set new standards for the integration of microbial processes in global biogeochemical analyses.

Mots-clés : marine nitrogen cycle,ocean deoxygenation,microbial ecophysiology,single cell activity,ecosystem modelling,ocean modelling
Projet ERC : RESYDE (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université d'Umeå — Pays : Suède — Rôle : PI
Acronyme de l'entité : UMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2413756.25 €

Scientists have long sought to understand how complex multicellular organisms generate their final form. Yet despite considerable progress, demonstrating predictive knowledge sufficient to re-engineer development according to design, remains a grand challenge. Addressing this challenge is not only fundamentally important, but also critical to the future of regenerative medicine and agriculture. Development depends on coordinated symmetry breaking events resulting from diverse mechanisms, ranging from the asymmetric localisation of molecules and stochastic processes within cells to the formation of morphogen gradients across a tissue. A mechanistic understanding of complex patterning processes therefore requires gaining knowledge on the molecular basis of multiple types of symmetry breaking events occurring at different scales. RESYDE will address this challenge by integrating information from diverse approaches into a virtual, dynamic cellular template. Predictive modelling will then be used to explain symmetry breaking at different scales sufficient to re-engineer the system by design. We will use the Arabidopsis flower as a model system and apply an interdisciplinary approach that utilises fine-scale perturbation techniques together with in vivo live-imaging of key regulators along with spatially mapped multi omics data, hormonal gradients and tissue mechanics to monitor responses at multiple scales. To leverage these data we will establish a 4D virtual cell template together with multiscale models to generate and simulate hypotheses in silico on the precise molecular origins of symmetry breaking events within the flower. We will apply our knowledge using a re-engineering approach to alter multiple floral symmetry breaking processes to better understand evolutionary floral architectural changes. Ultimately, RESYDE will provide a fundamental step change in our understanding of concerted symmetry breaking events across scales in complex multicellular contexts.

Mots-clés : flower development,meristem patterning,organ polarity,evo devo
Projet ERC : OxytocINspace (Horizon Europe, appel 2022, Synergy grants)
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 : 2650000.0 €

Orienting in space recruits brain mechanisms well conserved across mammalian species. Within the entorhinal-hippocampal network, a core system of spatially-selective cells supports spatial geometry computations. Yet, when navigating familiar surroundings, neural computations of space usually escape our attention. Instead, we parse space into socially meaningful territories. Territorial boundaries are social in nature since they capture the location of utilities available to individuals tied to group hierarchy and affiliation. How does our brain integrate geometry and territory? We propose that this process is regulated by the oxytocin (OT) system, acting on the entorhinal-hippocampal regions. OT, a hypothalamic neuropeptide known for its pro-social effects in mammals, modulates neural activity in the hippocampal formation, but its potential role in territorial representations has not yet been studied. Here, experts in complementary fields – social behaviors, spatial navigation, neurophysiology, anatomy, and cell signaling – will study brain similarities and differences of socio-territorial strategies in five mammalian species: bats, mice, rats, marmosets, and macaques. Our central goal is to investigate how neurons coding for space (e.g. place cells, boundary cells, grid cells) respond to perceived socio-spatial parameters of ownership, utility, and social hierarchies. We expect spatial cells to be sensitive to territorial manipulations (ownership, proximity, intrusion), regulated by OT in a context-dependent manner. OT inhibition may enhance territorial defense when territories are challenged (e.g., conspecific approaches or transgresses borders) and may sharpen territorial boundary representations. Conversely, OT stimulation could blur the boundaries of territorial perception. Our cross-species perspective will be the first to provide information on possible species-specific vs. shared neural mechanisms for territorial maps and OT-induced hippocampal plasticity.

Mots-clés : oxytocin,oxytocin receptors,entorhinal cortex,hippocampus,place cells,territorial behavior,rodents,bats,non human primates,social behavior