Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ANTSIE (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Durham University — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1472783.75 €

Antarctic sea ice is a critical component of Earth’s climate system. Seasonal fluctuations support unique ecosystems and impact planetary albedo, ocean-atmosphere exchanges of heat and climatically-active gases (e.g. CO2), and formation of intermediate and deep water masses which create the world’s largest sink of heat and carbon. The properties of the sea-ice pack are complex: despite its climatic significance, Antarctic sea ice is challenging to observe and to model, leading to low confidence in future projections in a warming climate. The geological record offers a longer-term context for recent trends. At the last glacial maximum (LGM) a likely doubling of Antarctic sea-ice extent relative to today is hypothesised to have driven an ocean drawdown of atmospheric CO2. However, a combination of sparse empirical datasets and uncertainties in sea-ice modelling means that the properties and climatic impacts of the LGM Antarctic sea-ice pack are poorly understood. The narrow focus of the geological record on key primary producers and grazers further limits our understanding of Antarctic ecosystem responses to changes in sea ice. ANTSIE will exploit a unique biological archive of Antarctic sea-ice conditions to generate a novel ecosystem perspective on the patterns and properties of sea ice during and since the LGM. ‘Antarctic mumiyo’ sequences are preserved remains of regurgitated stomach contents from snow petrels, which feed within and at the edges of the sea-ice pack. A network of mumiyo sequences, which sample across the climatically important Weddell Sea region, will be geochemically analysed to determine snow petrel diet and sea-ice properties with unprecedented century-scale resolution. The results will be used to evaluate new state-of-the-art simulations of the LGM sea-ice pack. By integrating multi-disciplinary perspectives, ANTSIE will provide new understanding of Antarctic sea-ice controls and impacts, to facilitate improved confidence in future project.

Mots-clés : paleoceanography,organic geochemistry,climate modelling
Projet ERC : ANTSIE (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : UK Research and Innovation — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : UKRI
Type d'entité : Recherche
Financement ERC de l'entité : 527145.0 €

Antarctic sea ice is a critical component of Earth’s climate system. Seasonal fluctuations support unique ecosystems and impact planetary albedo, ocean-atmosphere exchanges of heat and climatically-active gases (e.g. CO2), and formation of intermediate and deep water masses which create the world’s largest sink of heat and carbon. The properties of the sea-ice pack are complex: despite its climatic significance, Antarctic sea ice is challenging to observe and to model, leading to low confidence in future projections in a warming climate. The geological record offers a longer-term context for recent trends. At the last glacial maximum (LGM) a likely doubling of Antarctic sea-ice extent relative to today is hypothesised to have driven an ocean drawdown of atmospheric CO2. However, a combination of sparse empirical datasets and uncertainties in sea-ice modelling means that the properties and climatic impacts of the LGM Antarctic sea-ice pack are poorly understood. The narrow focus of the geological record on key primary producers and grazers further limits our understanding of Antarctic ecosystem responses to changes in sea ice. ANTSIE will exploit a unique biological archive of Antarctic sea-ice conditions to generate a novel ecosystem perspective on the patterns and properties of sea ice during and since the LGM. ‘Antarctic mumiyo’ sequences are preserved remains of regurgitated stomach contents from snow petrels, which feed within and at the edges of the sea-ice pack. A network of mumiyo sequences, which sample across the climatically important Weddell Sea region, will be geochemically analysed to determine snow petrel diet and sea-ice properties with unprecedented century-scale resolution. The results will be used to evaluate new state-of-the-art simulations of the LGM sea-ice pack. By integrating multi-disciplinary perspectives, ANTSIE will provide new understanding of Antarctic sea-ice controls and impacts, to facilitate improved confidence in future project.

Mots-clés : paleoceanography,organic geochemistry,climate modelling
Projet ERC : See-ACC (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Ghent University — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2380000.0 €

Anterior cingulate cortex is one of the largest riddles in cognitive neuroscience and presents a major challenge to mental health research. ACC dysfunction contributes to a wide spectrum of psychiatric and neurological disorders but no one knows what it actually does. Although more than a thousand papers are published about it each year, attempts to identify its function have been confounded by the fact that a multiplicity of tasks and events activate ACC, as if it were involved in everything. Recently, I proposed a theory that reconciles many of the complexities surrounding ACC. This holds that ACC selects and motivates high-level, temporally extended behaviors according to principles of hierarchical reinforcement learning. For example, on this view ACC would be responsible for initiating and sustaining a run up a steep mountain. I have instantiated this theory in two computational models that make explicit the theory's assumptions, while yielding testable predictions. In this project I will integrate the two computational models into a unified, biologically-realistic model of ACC function, which will be evaluated using mathematical techniques from non-linear dynamical systems analysis. I will then systematically test the unified model in a series of experiments involving functional magnetic resonance imaging, electroencephalography and psychopharmacology, in both healthy human subjects and patients. The establishment of a complete, formal account of ACC will fill an important gap in the cognitive neuroscience of cognitive control and decision making, strongly impact clinical practice, and be important for artificial intelligence and robotics research, which draws inspiration from brain-based mechanisms for cognitive control. The computational modelling work will also link high level, abstract processes associated with hierarchical reinforcement learning with low level cellular mechanisms, enabling the theory to be tested in animal models.

Mots-clés : anterior cingulate cortex,dopamine,cognitive control,reinforcement learning,cognitive,neuroscience,motivation,effort,prefrontal cortex
Projet ERC : VOILA (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Antibiotic resistance presents a growing threat to global health. The emergence of the superbugs is alarming: at current rates of increase, and without new intervention strategies, antibiotic resistance could cause a staggering 10 million deaths/year worldwide by 2050. Therefore, new approaches need to be developed to combat antibiotic resistance, particularly for the WHO’s priority pathogens which include the so-called ESKAPE family of dangerous drug-resistant bacteria. Recently, we developed a novel technology platform comprising a set of methodologies to semisynthetically modify the natural antibiotic nisin. In doing so we generated novel lipopeptide antibiotics with a much higher in vivo stability than the parent compound. These semisynthetic antibiotics possess a lipid II-mediated mode of action similar to nisin, which sets them apart from any current clinically-used antibiotic. During my ERC CoG, we have significantly improved these compounds, i.e. increased their antimicrobial activity and eliminated undesired haemolytic effects. Importantly, preliminary data shows that these antibiotics have a lower propensity to lose their potency due to antibiotic resistance development. I propose that these innovative lipopeptide antibiotics present a significant step forward in addressing the alarming threat of antibiotic resistance. However, to establish their commercial viability and broad applicability, the efficacy and preliminary safety of the new compounds need to be addressed. This can best be achieved via a PK/PD proof of concept study in appropriate animal models along with with a detailed evaluation of the business opportunity. The main objective of VOILA is therefore to establish both the technical feasibility and commercial viability of an entirely new class of lipopeptide antibiotics that is enabled by our innovative technology platform.

Mots-clés : antibiotics,antibiotic resistance,semi synthesis,mechanism of action,antibacterial assays,pd studies
Projet ERC : PeptideKillers (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Masaryk University — Pays : Rép. Tchèque — Rôle : PI
Acronyme de l'entité : MU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2315705.0 €

Antibiotic-resistant bacteria cause more than 700 000 deaths per year, and the forecast is 10 million per year in 2050. Moreover, emerging strains of bacteria resistant to all available antibiotics may lead to a global post-antibiotic era. Because of this threat, the WHO and the UN are encouraging the research and development of new treatments. The aim of this proposal is to design new peptides that selectively target and disrupt the membranes of pathogens but not those of human cells. To obtain such peptides, we will develop an innovative coarse-grained model of membranes and an original growth method, which will enable us to establish the relationship between peptide sequence motifs and their affinity to membranes with specific lipid compositions. Moreover, we will determine the critical peptide properties required for membrane disruption via the formation of transmembrane pores and spontaneous peptide translocation across membranes by devising new collective variables capturing these processes. Our computational advances will be complemented by experimental verification from peptide-membrane affinity measurements plus leakage and flip-flop fluorescence assays assessing membrane disruption. The most effective peptides will be evaluated for antimicrobial activity and human cell toxicity using growth inhibition and hemolytic assays, respectively. We will investigate mixtures of peptides for their synergistic increase in antimicrobial activity, and we will uncover the molecular mechanism of their synergism. The peptide behaviour will be quantified under equilibrium and more biologically relevant non-equilibrium conditions. The methods and knowledge obtained within this project will not only enable us to determine new peptides selectively killing bacteria, but will also enable the development of peptides targeted against membranes of enveloped viruses, cancer cells, or even cellular organelles with potential application as sensors, biomarkers, or therapeutics.

Mots-clés : computer simulations,phospholipid membrane,coarse grained model,lipid specificity,peptide,translocation,membrane pore formation,free energy calculation
Projet ERC : PLASREVOLUTION (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Comunidad de Madrid — Pays : Espagne — Rôle : Partner
Type d'entité : Organismes publics (hors enseignement & recherche)
Financement ERC de l'entité : 588522.02 €

Antibiotics are essential tools in modern medicine and are indispensable not only for the treatment of infectious diseases but also to support other key interventions such as surgery and cancer chemotherapy. However, the extensive and inappropriate use of antibiotics has fuelled the spread of resistance mechanisms in pathogenic bacteria, leading to the dawn of a post-antibiotic era. Plasmids play a pivotal role in the evolution of antibiotic resistance (AR) because they drive the horizontal transfer of resistance genes between pathogenic bacteria by conjugation. Some of these plasmid-bacterium associations become particularly successful, creating superbugs that spread uncontrollably in clinical settings. The rise of these clones is mainly constricted because plasmids entail a fitness cost when they arrive in a new bacterial host. This cost can be subsequently alleviated through compensatory adaptation during plasmid-bacterium coevolution. Despite the importance of this cost-compensation dynamic in the evolution of plasmid-mediated AR, it remains completely unexplored in clinical contexts. In this project I plan to bridge this gap by exploring the genetic basis underlying the evolution of plasmid-mediated AR in clinically relevant scenarios. We will study, for the first time, the intra-patient transmission, fitness cost and adaptation of AR plasmids in the gut microbiome of hospitalized patients (obj. 1). We will analyse the molecular mechanisms that determine the success of AR plasmids and bacterial clone associations (obj. 2). Finally, we will develop new technology to test how antibiotic treatments affect AR plasmids dynamics in the gut microbiome at an unprecedentedly high-resolution (obj. 3). This ground-breaking project will allow a new understanding of the evolution of plasmid-mediated AR in real life, opening new research avenues and providing a major step towards meeting one of the central challenges facing our society: controlling the spread of AR.

Mots-clés : antibiotic resistance
Projet ERC : PLASREVOLUTION (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 908791.98 €

Antibiotics are essential tools in modern medicine and are indispensable not only for the treatment of infectious diseases but also to support other key interventions such as surgery and cancer chemotherapy. However, the extensive and inappropriate use of antibiotics has fuelled the spread of resistance mechanisms in pathogenic bacteria, leading to the dawn of a post-antibiotic era. Plasmids play a pivotal role in the evolution of antibiotic resistance (AR) because they drive the horizontal transfer of resistance genes between pathogenic bacteria by conjugation. Some of these plasmid-bacterium associations become particularly successful, creating superbugs that spread uncontrollably in clinical settings. The rise of these clones is mainly constricted because plasmids entail a fitness cost when they arrive in a new bacterial host. This cost can be subsequently alleviated through compensatory adaptation during plasmid-bacterium coevolution. Despite the importance of this cost-compensation dynamic in the evolution of plasmid-mediated AR, it remains completely unexplored in clinical contexts. In this project I plan to bridge this gap by exploring the genetic basis underlying the evolution of plasmid-mediated AR in clinically relevant scenarios. We will study, for the first time, the intra-patient transmission, fitness cost and adaptation of AR plasmids in the gut microbiome of hospitalized patients (obj. 1). We will analyse the molecular mechanisms that determine the success of AR plasmids and bacterial clone associations (obj. 2). Finally, we will develop new technology to test how antibiotic treatments affect AR plasmids dynamics in the gut microbiome at an unprecedentedly high-resolution (obj. 3). This ground-breaking project will allow a new understanding of the evolution of plasmid-mediated AR in real life, opening new research avenues and providing a major step towards meeting one of the central challenges facing our society: controlling the spread of AR.

Mots-clés : antibiotic resistance
Projet ERC : AB-SWITCH (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : University of Rome Tor Vergata — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Antibodies are among the most widely monitored class of diagnostic biomarkers. Immunoassays market now covers about 1/3 of the global market of in-vitro diagnostics (about $50 billion). However, current methods for the detection of diagnostic antibodies are either qualitative or require cumbersome, resource-intensive laboratory procedures that need hours to provide clinicians with diagnostic information. A new method for fast and low-cost detection of antibodies will have a strong economic impact in the market of in-vitro diagnostics and Immunoassays. During our ERC Starting Grant project "Nature Nanodevices" we have developed a novel diagnostic technology for the detection of clinically relevant antibodies in serum and other body fluids. The platform (here named Ab-switch) supports the fluorescent detection of diagnostic antibodies (for example, HIV diagnostic antibodies) in a rapid (<3 minutes), single-step and low-cost fashion. The goal of this Proof of Concept project is to bring our promising platform to the proof of diagnostic market and exploit its innovative features for commercial purposes. We will focus our initial efforts in the development of rapid kits for the detection of antibodies diagnostic of HIV. We will 1) Fully characterize the Ab-switch product in terms of analytical performances (i.e. sensitivity, specificity, stability etc.) with direct comparison with other commercial kits; 2) Prepare a Manufacturing Plan for producing/testing the Ab-switch; 3) Establish an IP strategy for patent filing and maintenance; 4) Determine a business and commercialization planning.

Mots-clés : diagnostic kits,antibodies,point of care
Projet ERC : FuncMAB (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : École supérieure de physique et de chimie industrielles de la ville de Paris — Pays : France — Rôle : Partner
Acronyme de l'entité : ESPCI PARIS-PSL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 277000.0 €

Antibodies play an important role ensuring successful protection after vaccination. Upon injection, antigen-binding antibodies are generated to prime the host’s immune system for future encounters with the threat. These responses are highly heterogeneous, with each cell contributing with a single antibody variant to the complexity. Each antibody variant furthermore can recognize a different antigen/epitope with varying specificity and affinity. The immunological function induced is related to those parameters. Depending on the nature of the threat, required protective functional antibodies vary. Therefore, also each vaccination against those threads needs to trigger a specific functional antibody repertoire. Presently, induced functional antibody repertoires have not yet been studied sufficiently, mostly due to the lack of technologies that enable analysing these repertoires with high enough throughput and resolution. Consequently, the mechanisms behind the evolution of these functional repertoires, and the influence of vaccination on these repertoires remain poorly understood. An innovative technology combined with a methodical approach to vaccinations will enable the FuncMab research team to generate data sets needed for the understanding of immunological processes that result in different functional antibody repertoires. Herein, antibodies are analysed on the individual cell level in high-throughput using specific bioassays that target various antibody functions and their biophysical parameters, generating high-resolution data. These functional repertoires are followed over time and evolutionary changes can be linked to introduced vaccine variations, allowing a quantitative approach to study the changes within the repertoires. These in-depth data sets will not only allow understanding interactions between vaccine components and their generated immune responses, but also propels this project to the forefront of creating a new generation of successful vaccines

Mots-clés : bioanalytical science,antibody producing cells
Projet ERC : GCB-PRID (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998066.0 €

Antibodies secreted by B cells of the adaptive immune system establish an essential barrier against bacteria and viruses and their presence is the hallmark of protective vaccinations. B cells are licensed for their tasks during germinal center (GC) reactions and differentiation into antibody-secreting plasma cells. Unfortunately, B cell-derived autoantibodies and proinflammatory cytokines can cause or contribute to autoimmune diseases. While major transcription factor networks regulating protective (or pathogenic) GCB cell responses have been identified and characterized, little is known about the post-transcriptional regulation by RNA-binding proteins (RBP), whose number rivals that of transcription factors. We postulate that RBPs exercise critical post-transcriptional control over germinal center B (GCB) and plasmacytic cell physiology and we aim to identify and molecularly characterize these regulatory mechanisms. To this end, we will complement sophisticated genetic mouse models with novel cell culture systems. We will monitor RBP activity with fluorescent sensors and use proteomics to reveal RBPs regulating the protein abundance of critical mediators of GCB and plasmacytic cell fates. In addition, we will conduct genetic screens to uncover relevant functions of a short list of 40 RBPs, whose protein expression we found to differ significantly between GCB and mantle zone B cells. Ultimately, we will use cellular immunology and RNA biochemistry to elucidate how these RBPs exert their post-transcriptional control. Through the integrated power of our multi-disciplinary approach we will thus pinpoint and investigate the functions of key RBPs regulating the biology of GCB and plasmacytic cells. GCB-PRID promises to uncover profoundly new insights into post-transcriptional regulation of adaptive immunity. Thereby, this groundbreaking research aims to reveal novel molecular targets for the treatment of autoimmune diseases, whose incidence is steadily on the rise.

Mots-clés : germinal center b cell,autoimmunity,plasma cell,rna binding protein,post transcriptional gene regulation