Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SPACE (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université d'Helsinki — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2368459.0 €

Tumor progression is dependent on the ability of malignant cells to escape the recognition and attack by the host immune system. The development of more efficient cancer immunotherapies has been hampered by the perplexity of immune escape mechanisms. I hypothesize that tumor genetic drivers dictate the immune escape mechanisms, and that these mechanisms can be exploited to develop more effective immunotherapeutic strategies for patients with high-grade serous ovarian cancer (HGSC), the most common and lethal ovarian cancer. My group has developed an optimized algorithm based on homologous recombination (HR) DNA repair deficiency to enable clinically meaningful stratification of the complex HGSC genotypes. We will define the immunogenicity of the HGSC genotypes via profiling tumor somatic mutations and neoantigens, the cell-type specific gene expressions, and T/B cell receptor diversities using altogether >600 HGSC samples. Using a cutting-edge highly multiplexed technology and advanced image analysis, we will reveal the single-cell spatial landscapes of the tumor microenvironment in 200 immunogenetically-defined HGSCs. We will apply pioneering spatial analyses on the single-cell data and use artificial intelligence to uncover clinically relevant spatial biology of HGSCs. Via transcriptomic profiling of 384 spatial microregions, we will discover the detailed immune-escape mechanisms of the HGSC genotypes. For functional testing, we have developed a groundbreaking method to establish immune-competent patient-derived organoids (iPDOs), which faithfully recapitulate the patients' tumors. Using our high-throughput iPDO functional platform, we will test mechanism-specific immunotherapeutic approaches and capture the treatment responses at single-cell resolution. The discovery and functional targeting of the immune escape mechanisms gives us unprecedented potential to open new horizons in immunotherapeutic targeting of HGSC.

Mots-clés : spatial biology,cancer immunotherapies,ovarian cancer,immune evasion,tumor immune interactions,tumor genetics,immunogenomics,single cell profiling,tumor microenvironment,patient derived organoids
Projet ERC : STEXEU (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université nouvelle de Lisbonne — Pays : Portugal — Rôle : PI
Acronyme de l'entité : UNL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1493271.0 €

STEXEU investigates the impact of states of exception on democracy in early-twentieth century Europe. In the interwar years, and sometimes before, democratic rule came under strain across the continent. In explaining the rise of dictatorship, historians have generally pointed to forces that challenged the rule of law from without, such as fascism and communism. However, when faced with extraordinary challenges to state authority, the fin-de-siècle liberal legal order contemplated the suspension of constitutional norms through states of exception and emergency powers. During and after the First World War, governments became increasingly dependent on these legal instruments in a context of political instability. Their repeated use resulted in hybrid forms combining democratic and authoritarian features and sometimes (though not necessarily) paved the way to open dictatorship. STEXEU examines how the use of states of exception transformed the mentalities, practices, and interactions of state and non-state actors in charge of maintaining law and order. The project assesses eight national case studies: Spain, Portugal, Italy, Germany, Czechoslovakia, France, Britain, and Greece, which followed different trajectories in 1900-39 (some remained democratic, others not). Though it draws some cues from legal studies, STEXEU is above all a history project, which will revolutionise the voluminous juridical literature on states of exception by grounding this phenomenon in historical reality through a systematic analysis of primary sources. STEXEU promises to shed new light on the history of democracy and dictatorship, exploring the disregarded constitutional origins of authoritarianism that emerged from the bosom of the liberal regimes themselves. The relevance of this study transcends historiographical environments, enriching fields such as legal studies and political science and connecting with contemporary anxieties such as the rise of illiberal democracies.

Mots-clés : states of exception,democracy,dictatorship,liberalism,constitutions,social conflict,interwar decades,fascism,militarism
Projet ERC : DRYTREE (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université d'Helsinki — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1128957.5 €

One of the most pressing ecological questions is how trees and forests can survive in increasing intensity and frequency of droughts and extreme heat. Wide-spread drought-related tree mortality has been witnessed globally over the last decade and in 2022, Europe suffered from the worst drought in 500 years. Understanding and predicting the impact of drought and heat on tree mortality is limited due to lack of knowledge on the environmental conditions that lead to tree mortality. For the first time, it is feasible to quantify spatial and temporal tree mortality patterns and capture tree structure and species over large geographic regions at the individual tree-level. This enables me to aim to uncover environmental thresholds and key environmental drivers of drought- and heat-related tree mortality at the species-level for various forest biomes. Use of state-of-the-art remote sensing and deep learning methods allows me to capture where, when and what kind of trees (species, structure) have died for tens of millions of trees to increase our understanding of spatial and temporal tree mortality patterns. My approach uses laser scanning data to provide detailed tree 3D characterization and calculation of tree position within tree community (competition) and the landscape (water availability, microclimate). Then, combining these variables with information on tree xylem vulnerability, pest insects, soil temperature and climate, we can ultimately reveal species-specific environmental thresholds and key drivers of drought- and heat-related tree mortality. This research will open new horizons, bringing ecophysiology, remote sensing, forest ecology and entomology together, and developing methods to quantify drivers of tree mortality in much greater depth than has been possible to date. From these findings, we will be able to inform forest managers and policy makers which forests are at risk for increasing the resilience of future forests.

Mots-clés : tree mortality,drought,plant physiology,deep learning,laser scanning
Projet ERC : LEAD (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université du Ghana — Pays : Ghana — Rôle : Partner
Acronyme de l'entité : UG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 81725.0 €

Early adolescence is a key window for human development. Strategic timing of interventions during this life stage may seize opportunities and prevent risks; bolster the impact of earlier investments; and ease damages from previous adversity. Yet evidence on whether such programs can fulfil this potential, for which children, and through which channels, is scant, especially in low-resource settings, where 90% of the world’s 1.2 billion adolescents live. I will tackle these gaps by relying on a cohort of ~2,500 children approaching early adolescence. In 2015, this sample participated in a trial evaluating quality preschool education in Ghana and has been followed-up since: the program improved child development through middle childhood. I will re-randomise this sample at 12 years to test a parenting skills program to enhance early adolescent development through improved parenting support and parent-adolescent interactions. Children and parents will be re-interviewed when children are 13, 15, and 17 years through mixed-method data collection. Outcomes include adolescent social-emotional and academic skills, health (including stress biomarkers), and adult-life transitions. This data will allow testing dynamic complementarities between interventions during early childhood and early adolescence, or whether interventions in adolescence might compensate for earlier adversity in the short- and longer-term. Methodologically, these questions can be convincingly studied only if data are available for the same individuals over time, and if variations in exposure to early childhood and early adolescence programs are exogenously driven. This is the first study that addresses both requirements, providing a breakthrough. Heterogeneity by child gender and socioeconomic status, and mechanisms are further research foci. LEAD’s high-risk components are well-balanced by my in-depth knowledge of the field, methods, and study context, with high potential for scientific and societal impact.

Mots-clés : human development early adolescence early childhood intervention research child development child poverty inequality learning social emotional skills health health behaviour low and middle income countries gender social policy for children and adolescents in developing countries child development in context risk and resilience for children in situation of adversity lifecourse
Projet ERC : ComBiNE (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université Johann Wolfgang Goethe de Francfort-sur-le-Main — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499998.0 €

Nature is a remarkable pharmaceutical chemist. More than 50% of approved drugs are natural products (NPs) or have drawn inspiration from them. According to the central dogma of bacterial NP biosynthesis all transformations responsible for the formation and modification of a NP scaffold are carried out by enzymes encoded in a biosynthetic gene cluster (BGC). Sophisticated genome mining algorithms have been developed to identify NP BGCs in microbial genome sequences. These algorithms excel in recognizing canonical BGCs. Non-canonical BGCs associated with NPs that are not biosynthesized following textbook biosynthetic knowledge evade detection by state-of-the-art genome mining algorithms. We have identified alkaloids that undergo non-enzymatic transformations, thus defying the central dogma of NP biosynthesis. Bacteria likely employ specialized micro-compartments to facilitate these spontaneous reactions. The ComBiNE team will develop machine learning-based genome mining algorithms to systematically identify and characterize alkaloid BGCs that currently elude detection. These non-canonical pathways biosynthesize alkaloids independent of the ribosome and non-ribosomal peptide synthetases. We will focus on alkaloids that undergo non-enzymatic transformations in bacterial micro-compartments. We will establish a model system to study the level of compartmentalization necessary to facilitate spontaneous reactions. Insights gained from these studies will be used to engineer NP and primary metabolic pathways for the non-enzymatic fusion of tailor-made NPs or primary metabolites with complementary reactivity. Spontaneous reactions in bacterial micro-compartments can be harnessed for the fusion of two NPs with different targets to create bispecific chimeras to combat drug resistance or to fuse bioactive and homing components to mitigate off-target effects. The proposed research will inspire the development of biomimetic syntheses and expand NP chemical and biosynthetic space.

Mots-clés : bacterial natural products,alkaloids,genome mining,biosynthesis,structure elucidation,compartmentalized biosynthesis,non enzymatic reactions,spontaneous reactions,nmr,mass spectrometry
Projet ERC : SHARKS (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Université Johann Wolfgang Goethe de Francfort-sur-le-Main — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1586348.0 €

In the midst of the “sixths mass extinction event”, shark populations are declining with severe consequences for marine communities and ecosystem resilience. Diet is a key driver of shark evolution and a predictor of their extinction risk. Conservation efforts benefit from understanding past shark trophic ecology and how they coped with previous biotic crises. New analytical achievements in isotope proxy development allow the use of fossil teeth to reconstruct the trophic ecology of pre-Pleistocene animals. Using the novel Zn isotope proxy combined, for the first time, with other innovative trophic proxies (Ca and enameloid-bound N isotopes) on the same fossil and modern tooth samples, SHARKS will investigate the factor diet for a shark’s extinction risk, as well as food web changes across extinction events. Acknowledging the trophic position as an evolving trait, the project will pioneer a temporal approach, tracking trophic ecology of shark species through time. We will combine enameloid Zn, Ca and N isotopes with conventional dietary proxies (collagen C and N isotopes) in modern marine food webs to create a template for palaeoecological applications. Using this novel multi-proxy approach, we will investigate whether the emergence of serrated teeth in the Carcharodon lineage provided an ecological advantage for the modern great white shark (C. carcharias) over its now extinct ancestor with unserrated teeth C. hastalis. We will also test, from an ontogenetic perspective, the hypothesis of dietary competition between C. carcharias and the giant Otodus megalodon as potential factor of the latter’s extinction. Finally, we will explore the impact of the Cretaceous–Paleogene extinction event (66 Ma) on the trophic ecology of sharks and food web dynamics providing a hitherto unachievable view on one of the most devastating faunal turnovers in Earth’s history. The results will provide so far unattainable insights for conservation palaeobiology, ecology and palaeontology.

Mots-clés : diet,zinc isotopes,trophic levels,palaeobiology,sharks,calcium isotopes,diagenesis
Projet ERC : RE-CON-SENT (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université d'Helsinki — Pays : Finlande — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 158175.0 €

Consistent sentencing is a cornerstone of modern rule-of-law criminal justice systems. To enable judges to consider diverse circumstances at sentencing, legal frameworks provide judges with discretion (some countries also supply guidelines to increase consistency). The challenge is to provide judges with the right amount of discretion and guidance. This can be done in various ways, but there has not yet been any comprehensive assessment of these or of the limits they set across continental Europe. Attempts to evaluate the disparity of judicial practices run into the difficulty of identifying comparable cases. Typical sentencing studies consider behaviours to be the same if they fall within the same legal offence definition. However, each offence encompasses a wide range of behaviours, which impedes proper identification of disparities.  This project will redefine our understanding of sentencing discretion and its application by making a complex assessment of discretion within three dimensions: legal frameworks, judicial practices, and guidelines. I will analyse and classify approaches to structuring discretion in every European continental legal framework and quantify their discretion and punitivity. I will combine innovative data and methods – thorough court descriptions of criminal behaviour and natural language processing – with detailed administrative data to examine sentencing practices in two similar, yet also different countries: Finland and Czechia. I will design European guidelines for a single jurisdiction currently not employing them and experimentally evaluate their overall effectiveness, mechanisms and punitivity.  By deconstructing sentencing along these three dimensions and examining each in detail, I will paint a holistic picture of sentencing discretion, its extent, how it is structured across Europe, and its impact on punitiveness. The project will open multiple new research pathways and counterbalance the prevailing common-law-centric discourse.

Mots-clés : sentencing courts punishment discretion disparity guidelines
Projet ERC : IMMAGE (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Technion - Institut de technologie d'Israël — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

T lymphocytes play a central role in the immune defense against intruders, and support tissue homeostasis and function. Strikingly, an aged or dysfunctional T cell immunity is sufficient to promote organ aging and multiple age-related morbidities. In this proposal we hypothesize that there is a bidirectional relationship between T cells and their in vivo microenvironment that could develop into a vicious cycle under conditions of aging and disease. While a lot is known about the cellular mechanisms underlying T cell dysfunction with age, A profound understanding of how aging of the microenvironment impacts T cell immunity is missing. This work directly targets this gap to determine how the in vivo microenvironment in an aged mouse dictates T cells aging trajectories. Following on our preliminary findings, we will study two major mechanisms: (1) deficient metabolic support: we propose novel mechanisms by which stromal cells in the T cell zone of secondary lymphoid organs provide T cells metabolic needs for activation, and its failure in aged lymph nodes; and (2) toxic signals specific to the aged spleen that inhibit T cell metabolism and activation. Finally, we will investigate whether targeting these pathways would rejuvenate T cell immunity in vivo. The proposed study will discover unknown mechanisms supporting T cells metabolism in situ and will provide a causative link between T cell aging phenotypes and aging of their microenvironment. Finding new ways to rejuvenate immunity holds the promise for comprehensive and simultaneous targeting of multiple age-related pathologies.

Mots-clés : immunometabolism,immune aging,t lymphocytes
Projet ERC : ProtoSigns (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Université de la ville de Dublin — Pays : Irlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499653.0 €

Fossilised remains of protocells transitioning towards the first living organisms may be observable in the early rock record distorting our interpretation of biosignatures. Protocells – cellular structures existing prior to the emergence of life – would have comprised simple membranes and molecular machinery. The formation of complex protocells is poorly understood. The interpretation of fossilised microorganisms in the early rock record is steeped in controversy. The potential for abiotic microstructures to further complicate this interpretation has long been recognised but has not been systematically tested. Evidence suggests that prebiotic structures are very difficult to distinguish from microfossils. However, little is known about the chemical and physical characteristics of these ‘biomorphs’ that may enable us to tell the difference. This project will use a novel microfluidic approach to expand the experimental scope for formation of protocells of increasing complexity. Resulting microstructures will undergo silicification and diagenesis, the principal preservation pathway for early Archean microfossils. State-of-the-art analytical techniques will be used to characterise biomorphs, providing the first rigorous investigation of the feasibility of protocell preservation and how this might express in the geological record. These data combined with a predictive model and biological controls will allow for identification of key observables that will act as biogenicity indicators. Purported microfossils will then be examined and reinterpreted using the novel biosignatures. This project has the capacity to represent a paradigm shift in our fundamental understanding of the origin and evolution of life on Earth and possibly elsewhere in the Solar System. Collectively this will represent a major advance in our understanding of the geological record, providing the first comprehensive methodology to distinguish between abiotic, prebiotic, and biological microstructures.

Mots-clés : origin of life geobiology protocells
Projet ERC : DopamineLearnLoops (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Technion - Institut de technologie d'Israël — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499375.0 €

The brain’s ability to learn is arguably its most exceptional capacity. Learning in biological brains far surpasses machine learning and requires much less training. How does the brain accomplish this? Why is biological learning still better than the most advanced machine learning algorithms to date? According to the standard model of reward-based learning in the brain, a single error signal is broadcast from the dopamine system and used to update the entire network, implementing a simple form of reinforcement learning. However, the standard model fails to predict several recent experimental findings, leaving open the question of how learning is implemented in the brain. In this project, I propose a new theory of how the brain learns: learning is implemented by multiple dopamine-based learning systems working in parallel circuit loops. These loops relay partial error signals to specific processing areas and permit independent evaluation of the value of different features in the external environment as well as the internal state, enabling learning of complex tasks with multiple relevant features. The loops are engaged dynamically according to the demands of the task, enabling the system to be flexible for learning a wide variety of behaviours of varying complexity. The presence of multiple dynamic parallel learning loops might enable the ability to generalize learning, which is currently the hallmark of biological intelligence. We will use state-of-the art techniques under the framework of our theory to elucidate basic mechanisms underlying the functional circuitry of the learning system (Aim 1), how it operates under different behavioural dynamics (Aim 2), and what algorithm it implements (Aim 3). Success of this project will enable a novel understanding of how the brain learns complex tasks as well as pave the way for the development of new brain-inspired deep reinforcement-learning algorithms.

Mots-clés : dopamine,neural circuits,neural basis of learning,deep reinforcement learning