Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : EXECUT.ER (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 1999963.0 €

Programmed Cell Death (PCD) is fundamental to the development and health of multicellular organisms. However, our knowledge on developmentally controlled PCD in plants remains fragmentary, despite its undoubted significance for plant growth and reproduction. My team has established the Arabidopsis root cap as a novel model system for developmental PCD in plants. This model has enabled us to identify a gene regulatory network controlling the preparation of PCD. However, the molecular processes that terminate the vital functions of a plant cell during the final steps of PCD execution remain unknown. Exploiting the accessibility of the root cap for live-cell analysis of PCD execution, we obtained preliminary data revealing an unexpected succession of distinct membrane permeabilization events in which the endoplasmic reticulum breaks up before the central vacuole. I hypothesize that this sequential de-compartmentalization is the mechanism underlying the irreversible and orderly execution of PCD. Recent advances in several key technologies provide unprecedented opportunities to test this hypothesis and make a quantum leap in our understanding of the mechanisms carrying out PCD execution. I will employ correlative super-resolution light and electron microscopy to analyse PCD execution in unparalleled spatial and temporal resolution. RNA sequencing of single cells at the onset of PCD execution will provide information on the genes that are required for this rapid process. Advanced proteomics techniques will provide a direct route to identify proteins acting on membrane permeabilization during PCD execution. Lastly, multiplex and tissue-specific mutagenesis via innovative CRISPR screens will enable me to overcome genetic redundancy and lethality in the PCD context. The detailed understanding of plant PCD execution generated by this research program will shed light on a fundamental principle of plant development and open new avenues for crop improvement and protection.

Mots-clés : developmentally controlled programmed cell death,cell death execution mechanisms,breakup of subcellular compartmentalization,endoplasmic reticulum,central vacuole,plasma membrane,membrane permeabilization
Projet ERC : PROCELLDEATH (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 1499746.0 €

Programmed cell death (PCD) is a fundamental biological process that actively terminates a cell’s vital functions by a well-ordered sequence of events. In both animals and plants, various types of PCD are crucial for development, health, and the responses to various stresses. Despite their importance, only little is known about PCD processes and their molecular control in plants. Still, an intricate regulatory network must exist that renders specific plant cell types competent to initiate and execute PCD at precisely determined developmental stages. I recently established a powerful developmental PCD model system in Arabidopsis thaliana, based on a PCD process occurring during root cap development. This root cap model has the potential to revolutionize existing concepts of plant PCD, as it combines a precisely predictable PCD process in easily accessible cells on the root periphery with the abundance of resources available for Arabidopsis research. Exploiting the root cap system will enable me to tackle unresolved fundamental questions about the regulation of developmental PCD in plants: How do cells acquire PCD competency during differentiation? Which signals trigger PCD execution at just the right moment? What are the actual mechanisms that disrupt the vital functions of a plant cell? I will obtain answers to these questions through a comprehensive strategy combining complementary approaches, taking advantage of cell-type specific transcriptomics, forward and reverse genetics, advanced live-cell imaging, biochemistry, and computational modeling. Our unpublished data point to the existence of a common core mechanism controlling PCD not only in the root cap, but also in other vital organs including the vasculature, anthers, or developing seeds. Thus, this project will not only be significant to advance our knowledge on PCD as a general developmental mechanism in plants, but also to generate new leads to tap the so far underexploited potential of PCD in agriculture.

Mots-clés : developmental programmed cell death in plants,calcium,cell biology of programmed cell death,sub cellular dynamics,transcriptional regulation,computational modelling
Projet ERC : PyroPop (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Janssen (Belgium) — Pays : Belgique — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 729099.63 €

Programmed cell death is essential for homeostasis, and its deregulation contributes to human disease. Inflammasome-induced pyroptosis of infected macrophages contributes to host defense against infections, but the concomitant release of inflammatory danger signals and leaderless cytokines is detrimental in chronic inflammatory diseases. The central hypothesis of the PyroPop ERC Consolidator project is that inflammasomes are cytosolic platforms that couple pathogen sensing to multiple programmed cell death modes. This is based on our preliminary data showing that inflammasomes can be triggered to switch from inflammatory pyroptosis to programmed necrosis and non-inflammatory apoptosis. This suggests that the (patho)physiological outcomes of inflammasome activation may be modulated for therapeutic purposes. However, the molecular machinery and effector mechanisms of pyroptosis, inflammasome-induced apoptosis and programmed necrosis are virtually unknown. My objectives are (i) to explore the cleavage events and subcellular dynamics of pyroptosis by proteomics and high-resolution time-lapse microscopy; (ii) to clarify the molecular mechanisms of pyroptosis and inflammasome-controlled cell death switching; and (iii) to address how inflammasome-associated cell death modes impact on anti-bacterial host defense and chronic inflammatory pathology in vivo through the identification of pyroptosis-selective biomarkers and clinical analysis of pyroptosis-deficient mouse models. The central hypothesis in this regard is that inflammasome-mediated secretion of leaderless cytokines (such as IL-1β and IL-18) and danger signals may be mechanistically coupled to pyroptosis, but not apoptosis induction. By clarifying the mechanisms of inflammasome-controlled programmed cell death, this project may set the path for the development of an entirely novel class of inflammation-modulating therapies that are based on converting inflammatory pyroptosis into non-inflammatory apoptosis.

Mots-clés : pyroptosis,apoptosis,inflammasome
Projet ERC : ACTIVATE (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : CNRS Innovation — Pays : France — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 15000.0 €

Project ACTIVATE aims to bring to market real-time voice-transformation technologies based on ERC CREAM's research in emotion neuroscience, which can augment the value of spoken conversations by adding business-relevant control on emotional expressivity. For instance, in the context of a call-center conversation, our real-time voice transformations may make an angry client’s voice 10% less aggressive, reducing employee fatigue at the end of the day, or make an operator’s voice 10% more trustworthy, augmenting customer satisfaction after the call. Project ACTIVATE will (1) conduct market analyses and interviews of industrial players to identify relevant conversational situations in which the technologies can be tested (e.g. for a call-center, a customer calling to resiliate their contract), (2) identify precise conversation outcomes that have market value (e.g. retention rate after the call), (3) measure the impact of the voice transformation on these outcomes in a simulated test environment that is near the desired configuration in terms of performance and user performance and (4) use the technology’s measured impact on relevant variables (e.g. a X% increase of retention rate) to estimate the value of a minimally-viable product (MVP), to be taken to market by a startup company to be created at the end of the project.

Mots-clés : voice,emotion,signal processing,real time,neurosciences,digital voice assistants,call center,augmentative and assistive technology
Projet ERC : ACTIVATE (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
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 : 100000.0 €

Project ACTIVATE aims to bring to market real-time voice-transformation technologies based on ERC CREAM's research in emotion neuroscience, which can augment the value of spoken conversations by adding business-relevant control on emotional expressivity. For instance, in the context of a call-center conversation, our real-time voice transformations may make an angry client’s voice 10% less aggressive, reducing employee fatigue at the end of the day, or make an operator’s voice 10% more trustworthy, augmenting customer satisfaction after the call. Project ACTIVATE will (1) conduct market analyses and interviews of industrial players to identify relevant conversational situations in which the technologies can be tested (e.g. for a call-center, a customer calling to resiliate their contract), (2) identify precise conversation outcomes that have market value (e.g. retention rate after the call), (3) measure the impact of the voice transformation on these outcomes in a simulated test environment that is near the desired configuration in terms of performance and user performance and (4) use the technology’s measured impact on relevant variables (e.g. a X% increase of retention rate) to estimate the value of a minimally-viable product (MVP), to be taken to market by a startup company to be created at the end of the project.

Mots-clés : voice,emotion,signal processing,real time,neurosciences,digital voice assistants,call center,augmentative and assistive technology
Projet ERC : UNEARTH (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998971.0 €

Prokaryotes (archaea and bacteria) are the most abundant form of life both at present and throughout paleohistory and exhibit exquisite metabolic diversity, unmatched by eukaryotes. On early Earth, the absence of atmospheric oxygen led to the emergence of anaerobic microbial metabolisms such as methanogenesis, sulfate reduction, iron reduction, and denitrification. Non-isotope and isotope tools used to study ancient microbial life have provided evidence for each of these types of metabolisms in the rock record. However, there remains much uncertainty and debate regarding this evidence, primarily because of confounding effects of abiotic processes, and ambiguity in interpretation of isotopic signatures. This proposal aims to develop a robust biosignature for microbially mediated reduction reactions, that, in conjunction with existing tools, provides insight into ancient microbial activity in the rock record and establishes temporal constraints on the emergence of specific metabolic groups. To this end, I propose to use uranium (U) as an isotopic biosignature for microbial life. This pursuit is driven by recent work in my laboratory that has revealed a readily resolved difference between the isotopic signatures of enzymatically reduced uranium and abiotically reduced uranium. Combined with the ability of most microbial metabolic groups to catalyze U reduction, this finding raises the tantalizing possibility that uranium isotopic fractionation could serve as a biosignature for specific metabolic groups in the rock record. The establishment of a robust, bulk universal isotopic biosignature would be valuable to paleontologists, astrobiologists, and geologists because it would provide direct insight into the timing of emergence of specific metabolisms in ancient sedimentary environments on Earth.
Projet ERC : TURBOPOC (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149830.0 €

Proof of Concept TURBO FLOW Virtually all pipeline flows are highly turbulent. What is probably less well known is that the major part of the frictional losses in pipelines is caused by turbulence. Already at moderate speeds turbulence is responsible for a 50% drag increase while at high speeds (i.e. high Reynolds numbers) this figure can easily increase to 99%. Annual global pumping costs for oil pipelines alone amount to tens of billions of Euros. If instead the fluid could be maintained in the well-ordered “laminar” motion, pumping costs would drop dramatically. Up to now no methods existed that could convert fully turbulent flows in pipes back to laminar. In the course of the ERC project TURBOFLOW we discovered such a method and we demonstrated that under ideal laboratory conditions a fully turbulent flow can be completely relaminarized and as a consequence friction losses are reduced by as much as 80%. The aim is now to push this technology from the laboratory to practically realistic situations by testing the method in an oil pipe, closely matching the conditions in real pipeline flows.

Mots-clés : turbulence,turbulence control
Projet ERC : SYNEME (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 2212500.0 €

Proopiomelanocortin (POMC)- and Agouti-Related Peptide (AgRP)-expressing, i.e. melanocortin neurons in the hypothalamus, are key regulators of feeding behaviour, glucose metabolism, autonomic responses and higher cognitive functions. They represent targets for fuel-sensing hormones like leptin and insulin that thereby control key processes in systemic energy and glucose homeostasis. Importantly, resistance to these fuel-sensing signals is known to contribute to the current obesity and diabetes epidemic. Consequently, altered POMC- and AgRP-neuron regulation in obesity contributes to the development of numerous metabolic alterations. Although the melanocortin neurons as central regulators of metabolism have been classified according to the expression of their characteristic neuropeptides, it has only recently become clear that even within these populations they represent distinct heterogeneous neurons with respect to their physiological regulation and the biological responses governed by their specific downstream neurocircuits. However, the molecular nature of heterogeneous POMC and AgRP neuron populations, their specific neurocircuitry architecture and their specific functions still remain largely unexplored. Therefore, we will employ a wide array of state-of-the-art molecular systems neuroscience and modern mouse genetics approaches to define (1) the anatomical distribution, (2) molecular signature, (3) neurocircuitry architecture, (4) regulatory principles, (5) specific biological functions, and finally (6) novel druggable regulators of these specific POMC and AgRP microcircuits. We anticipate that the new knowledge generated will not only provide novel insights into the fundamental principles of CNS-dependent control of metabolism but could also lead to targeting these specific neurocircuits to develop novel, specific, tailor-made therapies for diverse aspects of metabolic diseases for which currently only insufficient treatment options are available.

Mots-clés : obesity,type 2 diabetes mellitus
Projet ERC : METAWARE (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 504992.36 €

Proposal summary. Understanding the psychological and neurobiological determinants of consciousness is fundamental. Yet, the main trend focusing on how the front of the brain (prefrontal cortex) interacts with the back (sensory cortex) for accessing perceptual contents limits our understanding of the information coding schemas underlying consciousness. Here, we explore these informational properties in adults and infants from 3 novel perspectives: sleep, self-consciousness and metacognition. First, we will study unconscious processes in the full absence of consciousness, including self-consciousness and metacognition, by focusing on the sleeping brain’s ability to process and learn information from its environment. While most studies on subliminal perception measured unconscious processes intermixed with conscious ones, studying their impact in the sleeping brain will provide new insights on a broader and more natural type of unconscious. Secondly, we will explore the fundamental issue of whether multiple agents can share information and each other’s conscious access mechanisms, without being aware of it. Using a novel approach called the “Reversed Perspective Paradigm”, we will study if access to conscious content can be determined by another agent’s actions and sensory processing while the agent is lured to believe she owns these access mechanisms. We aim at challenging the long-held conviction that consciousness is a paradigm of privacy, by breaking it using virtual reality and objective methods from psychology. Finally, we will attempt to answer the two fundamental issues of whether infants have a capacity for metacognition (do they know they know) and whether they experience self-consciousness (do they feel themselves as a unitary entity). Examining these self-reflection mechanisms, through behavioural and EEG techniques, will address the issue of whether humans in the initial state have a primitive self, or are actually unconscious about their own person.
Projet ERC : MetaboMARKER (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : CIC bioGUNE — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Prostate cancer (PC) is the most prevalent tumour type among men. The fraction of patients that exhibit disease recurrence can reach 15% and they face an uncertain future, since this type of tumour is prone to resist to subsequent therapeutic strategies. Current guidelines for treatment of PC include prostatectomy or radiotherapy as first line therapy for localized disease, and chemical castration followed by chemotherapy for recurrent PC. The lack of capacity to identify therapy responders vs. escapers in PC is one of the sources for its important mortality. The challenge resides in providing clinicians with a robust and affordable biomarker that informs about the success of first line therapy in localised PC, and that allows them to employ more intensive therapeutic strategies in high-risk patients. The development of such prognostic tools is urgently needed, since western societies are facing profound changes in the major PC risk factors, including age and obesity. Last, but not least, the cost of treating PC will progressively impose strong pressure in the public health system. In addition, patients that fail first-line therapy can be enrolled in subsequent therapies for up to a decade, and given their advance age (PC predominantly presents in the sixth decade of life) they frequently present endangering and costly co-morbidities and secondary effects. MetaboMARKER, a novel biomarker developed in the framework of the ERC-StG-336343-CancerMetab and already protected under a European patent, is able to differentiate patients harbouring a PC that would progress and potentially metastasize, from those that exhibited a disease that would not likely be a risk to their lives. Thus, MetaboMARKER may contribute to more efficient diagnosis, improved treatments and better distribution of funds in disease management. The aim of the present PoC is to further develop the final biomarker for its commercialization and define the best exploitation strategy plan.

Mots-clés : prostate cancer prognosis,biomarker,metabolism,metastasis,disease recurrence,personalized medicine
Projet ERC : ComplexAssembly (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : European Molecular Biology Laboratory — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1240537.91 €

Protein complexes are central to many cellular functions but our knowledge of how cells assemble protein complexes remains very sparse. Biophysical and structural data of assembly intermediates are extremely rare. Particularly in higher eukaryotes, it has become clear that complex assembly by random collision of subunits cannot cope with the spatial and temporal complexity of the intricate architecture of many cellular machines. Here I propose to combine systems biology approaches with in situ structural biology methods to visualize protein complex assembly. I want to investigate experimentally in which order the interfaces of protein complexes are formed and to which extent structures of assembly intermediates resemble those observed in fully assembled complexes. I want develop methods to systematically screen for additional factors involved in assembly pathways. I furthermore want to test the hypothesis that mechanisms must exist in eukaryotes that coordinate local mRNA translation with the ordered formation of protein complex interfaces. I believe that in order to understand assembly pathways, these processes, that so far are often studied autonomously, need to be considered jointly and in a protein complex centric manner. The research proposed here will bridge across these different scientific disciplines. In the long term, a better mechanistic understanding of protein complex assembly and the structural characterization of critical intermediates will be of high relevance for scenarios under which a cell’s protein quality control system has to cope with stress, such as aging and neurodegenerative diseases. It might also facilitate the more efficient industrial production of therapeutically relevant proteins.

Mots-clés : protein complex assembly,local translation,cryo electron tomography,quantitative mass spectrometry,nuclear pore complex