Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : AC3S (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Université de Stockholm — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1830134.0 €

Interactions between anthropogenic aerosol particles and clouds are the largest source of uncertainty in the historical radiative forcing of climate. Aerosol effects on tropical deep convective clouds could constitute a major component of this forcing, but the underlying physical mechanisms are poorly understood, and the associated global climate forcing has not been rigorously quantified before. These knowledge gaps have been highlighted as an urgent research challenge in recent assessment reports by the Intergovernmental Panel on Climate Change (IPCC) and the World Climate Research Programme. AC3S seeks to address this challenge by applying state-of-the-art observational and modeling techniques that span the disciplines of aerosol-cloud interactions and climate science. First, I will perform regional analysis of satellite observations, in-situ aircraft measurements, and high-resolution numerical simulations to investigate hypotheses about the physical mechanisms that govern the interactions between aerosols and tropical deep convective clouds. Second, I will analyze global satellite observations to attain the first rigorous assessment of global climate forcing from these aerosol-cloud interactions. Finally, I will synthesize the evidence and quantify the implications of the results for Earth’s climate sensitivity to carbon-dioxide forcing and 21st century global warming. This integrated approach will advance the field of aerosol-cloud-climate interactions and ensure that the results are immediately accessible to a broad audience, including policymakers and future IPCC assessment reports.

Mots-clés : aerosol cloud interactions,atmospheric convection,aerosol radiative forcing of climate change,climate sensitivity
Projet ERC : TransPIre (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université de Stockholm — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1634250.0 €

Two recent revolutions in time-domain astronomy are transforming our understanding of stellar evolution in the most massive regime: the detections of gravitational waves (GW) from binary black holes, and the discovery of new and rare classes of supernovae from wide-field transient surveys. With this, a long-standing prediction from stellar evolution theory is gaining new relevance: that stars with He cores above ~35 solar masses will encounter an instability due to pair-production, resulting in either a series of pulsations and corresponding mass ejections, or the complete disruption of the core in a pair-instability supernova. GW detectors can search for the resulting gap in the black hole mass distribution, while supernova surveys can constrain the occurrence of the pair-instability phenomenon in the low-redshift universe by searching for the associated transients. With the upgrade in survey volume in the 2020s by the LSST project, we have an unprecedented opportunity in finding and studying such rare transients, but first need to solve the substantial needle-in-haystack problem of identifying the relevant candidates from a stream of several million alerts per night. TransPIre will address this by drawing on both the analysis and properties of the current state-of-the-art supernova samples being collected, as well as theoretical expectations of (pulsational) pair-instability supernovae, to build the necessary identification software and deploy it on the LSST alert streams to select the best candidates for follow-up and further analysis. As a result, we will uncover the relation between pair-instability phenomena and extreme transients such as superluminous supernovae, identify which interacting transients have mass-loss histories consistent with pulsational pair-instability mass-loss, and either find the first bona-fide pair-instability supernova in the low redshift universe or place the strongest constraints to date on their occurrence.

Mots-clés : supernovae pair instability transient surveys massive stars
Projet ERC : METspread (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université de Bâle — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UniBasel
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2028936.0 €

Breast cancer is the most common malignancy in women with globally over 600’000 deaths per year. While cancer diagnosis before metastasis is often associated with a favourable prognosis, due to surgical and new therapeutic approaches, once metastasis is initiated, the survival rates decline significantly. However, the understanding of this last and most detrimental phase of cancer remains at a low resolution, reflected by the lack of metastasis-targeted therapeutic options. In fact, most of the studies have focused on the understanding of primary tumour states and their relationship to metastasis. Recently, it has emerged, however, that secondary seeding from metastatic deposits to new sites plays a role in cancer spread. We made an unexpected discovery that the cancer cells metastasised to different sites display dramatically distinct molecular and functional properties, thereby having diverse impacts on cancer progression. This highlights a previously underappreciated role of secondary seeding and emphasises the need to study metastasis at a higher resolution. Indeed, metastasis is an evolutionary process that occurs across various organs and timescales, yet its spatiotemporal progression is a black box. To this end, we will use cutting-edge technologies such as evolving barcodes and niche-labelling systems and state-of-the-art in vivo models to identify 1) different spatiotemporally controlled metastatic behaviours, together with 2) the associated alterations in the metastatic niche and 3) specific niche-cancer crosstalk that guides the cancer expansion and metastatic properties. This project will create a first spatiotemporal cellular model of metastasis, which will reveal how the metastatic behaviour at different sites is shaped during metastatic progression. Our research has a long-term ambition to design new therapeutic approaches informed by the metastatic profile and temporal biomarkers in patients.

Mots-clés : cancer,metastasis,metastatic niche,breast cancer,niche
Projet ERC : MultiPRESS (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1621913.0 €

Regional quantification of cardiovascular pressure gradients is critical for diagnosis, treatment planning, and risk prediction of many cardiovascular diseases. Still, for a large number of conditions, non-invasive assessment is obstructed by inherent method limitations, and a wide range of cardiovascular instances exist where regional pressure behaviour remains unexplored. The MultiPRESS project main objective is to develop a novel imaging paradigm for non-invasive assessment of cardiovascular pressure gradients, overcoming critical limitations of existing techniques through a unique multiscale approach. Doing so, the MultiPRESS project seeks to – for the first time – extend non-invasive hemodynamic risk prediction into previously inaccessible cardiovascular domains, advance our knowledge of complex hemodynamic behaviour, and tackle remaining urgent clinical challenges across the heart, aorta, and brain. Using deep integration of advanced full-field magnetic resonance imaging (4D Flow MRI), super-resolution networks, and physics-informed image processing, a set of core developments will allow for unique, comprehensive image-based pressure gradient assessment across (1) spatial (big/small vessels), (2) temporal (fast/slow flows), and (3) flow (laminar/turbulent) scales, with developments consistently validated in dedicated in-silico, in-vitro, and in-vivo cohorts. These developments will then be utilized on a set of core applications across (4) cardiovascular scales (heart/aorta/brain), addressing urgent clinical challenges and extending image-based pressure gradient quantification through previously inaccessible domains. Based in a unique multidisciplinary setting at Scandinavia’s largest university hospital, successful delivery of MultiPRESS will represent a paradigm shift in clinical hemodynamic risk prediction, and pave way for new scientific knowledge revitalizing risk stratification of complex cardiovascular disease across the heart, aorta, and brain.

Mots-clés : cardiovascular imaging,magnetic resonance imaging,hemodynamics,pressure gradients,super resolution machine learning
Projet ERC : E-CTRL (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1494669.0 €

Protein signaling in cells is precisely coordinated in space and time. Molecular chemogenetics, optogenetics, and biosensors have generated a scientific revolution enabling the spatiotemporal codes of protein signaling in single cells. However, it is a great challenge to study protein dynamics in a physiological multicellular environment due to the extensive variability in protein signaling within individual cells, as well as the sparsity of driver cells responsible for a specific physiological process. To build causal relationships between proteins and multi-cellular behavior, we will develop broadly applicable technologies by engineering proteins enabling the control of target proteins with light, exclusively in the relevant driver cell subpopulations. These approaches can be used in any biological field in which protein signaling is critical for multi-cellular behavior, but here we will focus on three different stages of a challenging neurobiology process. Upon sensory experience, for example, by learning a new task, only the subsets of neurons within a corresponding brain region switch to the active state. It is largely unknown how proteins that are activated in these sparsely activated neuronal circuits operate in space and time. Our technologies will enlighten the spatiotemporal dynamics of proteins in active neuron subpopulations responding to certain learning tasks in mice. Understanding such learning neuronal circuit responses at the molecular level will pave the way to develop new therapeutic approaches for brain disorders including epilepsy, depression, and autism spectrum disorders.

Mots-clés : biosensors,molecular optogenetics,chemical biology,protein engineering,protein switches,engineered allostery,neural circuits,synaptic plasticity,cellular circuits
Projet ERC : D-MAP (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 941310.0 €

Numerous mucosal vaccines and IgA-based monoclonal antibodies aimed at a robust immunity within the respiratory tract are in development to combat viral endemics and pandemics. However, investigations into humoral immunity have predominantly focused on circulating antibodies, particularly those of the IgG isotype. This has left a significant void in our understanding of the role of mucosal IgA proteoforms in conveying effective immune protection. This crucial knowledge gap deprives vaccine and antibody development of crucial determinants or immune characteristics to replicate.  In response to this, we will conduct in-depth investigations of mucosal IgA including in vitro and in vivo functional evaluations. We will capitalize on recent advances in liquid chromatography and mass spectrometry-based approaches for the detailed characterization of mucosal IgA clonal repertoires and glycosylation profiles, a field that has remained completely unexplored until now, B-cell receptor sequencing, monoclonal IgA glycoengineering and in vitro functional assays. We will take advantage of our unparalleled biobank of human nasal secretion samples with clear documentations of infection outcomes on an individual level. What sets our approach apart is thereby the unprecedented molecular-level characterization of IgA, directly linked to their in vitro functionality and pre-defined clinical outcomes, which clearly surpasses current state-of-the-art.  By harnessing our in-depth characterization of mucosal IgA coupled to functional traits, we will generate IgA templates with enhanced binding and neutralization capabilities as well as functionally advantageous Fc effector potencies. Our overarching aim is to provide molecular-level blueprints for protective monoclonal IgA-antibodies, enabling the fine-tuning of vaccine formulations and monoclonal antibody generation with a higher degree of accuracy, ultimately enhancing their efficacy and safety.

Mots-clés : mucosal immunity,iga clonal repertoire,iga glycosylation
Projet ERC : Tightly Controlled (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2318778.0 €

One of the most fascinating aspects of salamander regeneration is the level of precision at which restoration of complex structures occurs. How the recovery of form and function is sensed at a cellular level leading to appropriate termination of regenerative programs remains largely unknown. This is partly due to technical challenges of studying cellular events at a high-resolution during regeneration and establishing a constitutive link between cell behavior, tissue architecture and function. Here, I propose taking an interdisciplinary approach that combines gene editing, deep-tissue imaging, force measurements and spatial -omics to overcome these barriers. My goal is to gain holistic understanding of regeneration by integrating molecular, cellular, mechanical and functional parameters. Specifically, I aim to explore the role of tight junctions and mechanical cues in sensing and relaying macroscale information to adapt cellular events as the regeneration unfolds. We will utilize the newt Pleurodeles waltl and heart regeneration as an ideally suited regeneration context where I recently showed that the injury response by the epithelial-like covering called epicardium and the dedifferentiating cardiomyocytes are closely coordinated to replenish the lost muscle. By combining long term intravital cell tracking, mechanical characterization and ultrasound imaging with tight junction manipulations and mechanical perturbations we will 1) define cell dynamics and regenerative state transitions 2) test whether unique expansion in the tight junction protein Claudin-6 sequence that extends its N-terminus is protective against overproliferation and 3) map the physical properties controlling the termination of regenerative programs. Our results will identify mechanisms underlying the tight control of regeneration and bring new insights into the function of Claudins that are frequently dysregulated in cancer, opening new venues in regenerative medicine and cancer research.

Mots-clés : salamander,heart regeneration,tight junctions,claudin,cancer
Projet ERC : MoodMAP (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499999.0 €

Reproductive mood disorders (RMDs), including premenstrual disorder and postpartum depression, have a significant impact on women and their families, contributing to the well-known gender gap in mental health. However, effectively diagnosing and treating RMDs remains an ongoing challenge. These conditions are closely tied to hormonal changes during menstruation and childbirth, indicating a shared vulnerability. While the precise mechanisms are not yet fully understood, emerging data, including my work, supports the hypothesis that genetic predisposition, chronic inflammation, and metabolic dysfunction play pivotal roles in the development of RMDs. The MoodMAP project aims to discover novel molecular markers for RMDs, provide insights into the biological factors influencing varying vulnerabilities to mood disorders in women, and enhance diagnostic, preventative, and treatment strategies for RMDs. The endeavor leverages three Nordic population-based cohorts a) to DEPICT a comprehensive architecture of RMDs by integrating genomic, inflammatory proteomic, and metabolomic data; b) to TRIANGULATE evidence for identifying biologically functional and causal biomarkers using cell data manipulated with hormones and advanced epidemiologic methods; c) and to PREDICT treatment outcomes, including treatment resistance and subsequent suicidal behavior, through multi-omics data and machine-learning methods. MoodMAP adopts an innovative approach by studying both RMDs together, aiming to uncover the biological basis of female vulnerability to mood disorders through multi-omics data. By integrating advanced omics techniques, hormone-manipulated cell data, and cutting-edge epidemiologic and statistical methods, MoodMAP holds the potential to understand the psychiatric sensitivity associated with sex hormones, drive transformative changes of diagnosis, prevention, and treatment strategies for RMDs, and ultimately contribute to the reduction of the gender gap in mental health.

Mots-clés : premenstrual disorders postpartum depression women s mental health reproductive mood disorders psychiatric epidemiology
Projet ERC : MINDSIM (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

The mere presence of another person automatically triggers powerful processes of belief computation in our brains. This spontaneous and well-established Theory of Mind (ToM) ability is considered vital for efficient social interactions. Yet, we still know little about the mechanisms allowing the brain to automatically, and without apparent mental effort, keep track of who is believing what. I argue that the role of modeling others’ attention is an overlooked and a key factor in this process. I propose the novel hypothesis that the brain makes use of an implicit model of others’ attention, recently characterized by me, featuring the simplified construct of implied motion ‘beams’ linking agents to attended objects, to support automatic belief computations. In Aim 1, supported by preliminary behavioral results, I will determine whether people perceive others’ beliefs as an implied motion between agents and belief targets, and whether this mechanism plays a functional role in spontaneous ToM. Aim 2 will apply multimodal neuroimaging and neurostimulation to define the underlying neural representations. Previous work suggests that spontaneous ToM and visual motion processing is impaired in autism. Aim 3 will examine the hypothesis that failure to engage visual motion systems when perceiving others’ beliefs explains the reduced spontaneous ToM in autism. Critically, the serotonin releasing agent MDMA is suggested to enhance both visual-motion and ToM processing. In Aim 4, I will therefore employ a double-blind, active-placebo-controlled trial to test the hypothesis that MDMA can improve spontaneous ToM in autism by upregulating this motion-based mechanism. Using an innovative behavioral intervention, I will utilize MDMA’s known effects to promote motion-encoding of others’ beliefs. My results will reveal fundamental principles of social cognition and may provide a long sought-after mechanism-focused intervention to facilitate social cognition in autism.

Mots-clés : social cognition,theory of mind,attention,autism,fmri,psychopharmacology,mdma,intracranial eeg,electrical brain stimulation
Projet ERC : SHADES (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université de Turku — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498858.0 €

SHADES holds great potential for scientific breakthroughs in unravelling the complexities of school bullying by advancing the understanding of heterogeneous youth who bully their peers and persistent bullying, genetic underpinnings behind them, and life-course of different types of bullies. This will help develop targeted interventions to tackle bullying more efficiently and thus prevent long-lasting suffering of victimized youth and mitigate consequences for bullies.In order to move the field forward, there is an urgent need to shift from studying average effects of bullying or bullies as a homogenous group towards inspecting subtypes among youth tormenting their peers. SHADES addresses gaps in the literature through four objectives. First, it will build a comprehensive understanding of characteristics, motives, and social cognitions of heterogeneous bullies (WP1). Second, by systematically assessing persistent bullying it will draw a nuanced picture of factors influencing continuance and discontinuance of bullying (WP2). Third, it will reveal the underlying polygenic factors contributing to heterogeneity among perpetrators and persistent bullying (WP3). Fourth, it will construct a holistic view of how different types of bullies adapt to various areas of life (e.g., work, relationships) as they transition into adulthood and how genetic factors influence the adjustment (WP4). SHADES will 1) develop two novel instruments: a mobile test of implicit attitudes and motives and an eye-tracking experiment of social cognitions, 2) collect new data (self- and peer-reports + experimental data), and 3) combine existing data into a globally unique longitudinal dataset (survey in childhood, adolescence, and adulthood + genetic data + register data from the same individuals). This enables drawing a comprehensive picture of different types of bullies and persistent bullying at the genetic level, in the short-term (through middle school), and in the long term (up to adulthood).

Mots-clés : bullying perpetration,psychosocial adjustment,genetic confounding