Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : YMPACT (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Magyar Agrár- és Élettudományi Egyetem — Pays : Hongrie — Rôle : Partner
Acronyme de l'entité : SZIU;SZIE;MATE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 27399.11 €

Dramatic migrations in the third millennium BC re-shaped Europe, modifying its economy, society, ethnicity and ideological structure for ever. The best incentive proxy are populations that moved from the steppes of Russia, spreading as far west as Hungary, implanting a pastoral economy with widespread innovations. These dynamic people covered thousands of kilometres within a few centuries, and organised direct physical relations over the steppes for the first time. This synchronism is promoted by a society organised to fit to this lifestyle, with new herding techniques, likely use of wagons and domesticated horses, and a protein-rich diet, whose adaptive advantages are evident from the physical record in human skeletons and territorial extensions. This is the Yamnaya complex, whose impact remains visible today in the European gene pool and apparently the propagation of Indo-European languages. This international and interdisciplinary project examines the data from 320 excavated burial mounds and c.1350 burials to calibrate these changes, also against a control sample of supposedly local and neighbouring populations. The archaeological, biological and environmental information allows large, new datasets to be built, whose systematic interrogation and modelling should reveal the formative processes behind these changes. Assessing funeral archaeology, material culture, and exchange pattern defines their culture and impact. Scientific analyses of skeletons expose relations of origin, degrees of consanguinity, diet, and histories of individual mobility over single lifetimes with new precision and replicability. They should also act as proxy datasets for environmental changes using further analytical techniques in a context of landscape evolution. Diachronic patterns within these sets should link with aspects of the internal social dynamics, such as the creation of new status positions, visible later in the Pan-European Corded Ware and Bell Beaker groups.

Mots-clés : migration,ancient dna,bio anthropology,isotope geochemistry,landscape archaeology,palynology,pedology,cultural heritage,language change
Projet ERC : FluoSurf (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 135111.0 €

Droplet-based microfluidics is a key emerging technology for the miniaturization and automation of biochemical assays. The limiting factor for industrial applications of the technology is not the device aspect but rather the robust control of emulsion formulations to be used in these devices. Existing formulation solutions available on the market are far from being mature enough to fully convince and satisfy the end-user. The ERC project SOFI has resulted in the fundamental understanding of the dynamics of surfactant with two key results on emulsification efficiency and on retention efficiency. We identified that the flaw in the formulations results from a fundamental misunderstanding of the surfactant properties. We have a competitive technical advantage from our results of the ERC project SOFI in terms of fundamental understanding of the dynamics of surfactant to explain the origin of failure of the current formulations and to propose alternative solutions. We will provide high-quality and high-added value formulations, adapted to the industrial landscape of droplet-based microfluidics with an non-restrictive level of details on the elements of the formulation for the customer. We will characterize the molecules using our cheap and newly developed methods for a quantitative determination of the formulation performance. The aim of the proposed Proof of Concept are therefore to (i) improve our product technical and economic properties, (ii) finalize the transfer of our technology from the laboratory to the market and (iii) to start business and product commercialization.

Mots-clés : surfactant,droplet based microfluidics,screening
Projet ERC : UniMab (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : PI
Acronyme de l'entité : IRCCS
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2345625.0 €

Duchenne muscular dystrophy (DMD) is a devastating incurable disease, affecting thousands with heavy burden on health systems. This project combines the development of a safe, “immune-privileged cell” with genetic engineering to correct many dystrophin gene mutations for an efficacious and cost affordable therapy. The applicant pioneered systemic intra-arterial transplantation of mesoangioblasts (blood vessel-derived progenitors) that proved safe in DMD patients and is being implemented for efficacy. However, this personalised approach would prove prohibitively expensive for healthcare systems, as pricing of successful gene therapies is showing. We made the striking observation that human mesoangioblasts can be indefinitely expanded with a novel culture medium, even after genetic manipulation and cloning. Cells will be first genome edited to delete endogenous HLA (β2-microglubin and class II CTA) while inserting tolerogenic HLA-E, fused to β2-microglubin and, as safety device, the Herpes Simplex Thymidine Kinase suicide gene with truncated NGF receptor for selection. Edited clones will be checked for genome integrity. Selected clones will be engineered to express a small nuclear RNA (snRNA) that causes skipping of a given exon of the dystrophin gene. Due to the syncytial nature of muscle fibres, the snRNA also enters and corrects the genetic defect in neighbouring, dystrophic nuclei, thus amplifying of one log the therapeutic effect. Five different cell lines would correct the mutation in 60% of DMD patients. The cell lines will be transplanted in humanized DMD mice and assessed for the ability to escape immune surveillance and to differentiate in dystrophin expressing myofibers, establishing pre-clinical safety and efficacy for an off the shelf, affordable product. The applicant has unique expertise to successfully complete this project, whose strategy may be expanded to other recessive monogenic diseases, for a ground breaking impact in regenerative medicine.

Mots-clés : adult stem cells,genome editing,gene correction,exon skipping,immune privilege,cell proliferation
Projet ERC : 4-D nanoSCOPE (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Universitätsklinikum Erlangen — Pays : Allemagne — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2837980.0 €

Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function. To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo. The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.

Mots-clés : bone structure,bone disease,bone mechanics,x ray microscopy,image reconstruction,correlative microscopy,osteoporosis,arthritis,deep learning
Projet ERC : 4-D nanoSCOPE (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Fraunhofer Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FHG
Type d'entité : Recherche
Financement ERC de l'entité : 6773605.0 €

Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function. To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo. The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.

Mots-clés : bone structure,bone disease,bone mechanics,x ray microscopy,image reconstruction,correlative microscopy,osteoporosis,arthritis,deep learning
Projet ERC : ACCENT (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Due to antibiotic resistance, there is now great interest in the development of antibody-based therapies against bacterial infections, for instance via antibodies that boost the host immune system. In order to kill bacteria, antibodies should trigger activation of the complement cascade, which forms bactericidal Membrane Attack Complex (MAC) pores and strongly enhances phagocytosis. Although the power of complement could be exploited for antibody therapies, such developments are hampered by our limited insights into the mechanisms underlying antibody-dependent complement activation on bacteria. My team has developed unique assays to study complement activation on bacteria. In this proposal, we will combine our function-driven approaches with novel B cell sequencing methods to identify anti-bacterial antibodies with strong complement-activating potential. We will develop novel approaches to identify the variable (VH:VL) sequences of human antibodies that recognize whole bacterial cells. After FACS sorting of memory B cells or yeast Fab display, we will use multi-well functional assays to select monoclonal antibodies driving potent complement activation and subsequent killing of E. coli (via neutrophils or MAC). Thanks to our unique tools and unprecedented insights, we are in an unique position to decipher basic mechanisms by which antibodies induce bacterial killing via neutrophils or MAC. We will combine live-cell imaging and structural approaches to determine how bactericidal antibodies assemble lethal MAC pores in the bacterial cell envelope. Finally, we will explore the design of potent antibody combinations and study the mechanisms by which antibodies steer different effector functions, both in the context of clinical and non-pathogenic E. coli strains. Altogether, this grant will lead to fundamental knowledge about the functioning of the immune system and provide a biological basis for the development of antibody-based therapies against bacteria.

Mots-clés : antibodies,complement,phagocytosis,membrane attack complex,gram negative bacteria
Projet ERC : FlyGutHomeostasis (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : PI
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498964.0 €

Due to its remarkable self-renewing capacity, the fly gut has recently become a prime paradigm for studying stem-cell function during adult tissue homeostasis. This capacity for self-renewal relays on the proliferative activity of the intestinal stem cells (ISC), which is tightly coupled with cell loss to maintain intestinal homeostasis. ISC proliferation is controlled by multiple local and systemic signals released from the ISC niche (enterocytes (ECs), enteroendocrine (EE) cells, enteroblasts (EBs), and visceral muscles (VMs)) and non-gastrointestinal (non-GI) organs. Despite the physiological divergence between insects and mammals, studies have shown that flies represent a model that is well suited for studying stem cell physiology during ageing, stress, and infection. As a saturating approach to identify local and systemic signals controlling intestinal homeostasis in steady-state and challenged conditions, RNAis will be used to known down all genes encoding secreted peptides specifically in ECs, EEs, or VMs and all genes encoding transmembrane and membrane-associated proteins in the VMs. The proposed screens should identify novel intra- and inter-organ circuitries allowing communication between the gut and other organs to provide organismal health. In addition, the systematic knockdown of secreted peptides from the ISC niche could identify gut-derived signals that couple changes in environmental inputs, such as nutrient availability, with systemic changes in feeding behavior, energy balance, and metabolism. Since large-scale approaches are not feasible in vertebrate models, the signals identified in the above screens could potentially reveal novel couplings contributing to mammalian GI homeostasis and disease. The final part of the proposed project aims a deciphering the molecular signals coupling epithelial fitness with ligand-independent TNFR activation to control ISC division and epithelial turnover in steady-state, challenged and pathological conditions.

Mots-clés : drosophila,genetics,inter organ communication,intestinal stem cells
Projet ERC : FeelAgain (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : University of Belgrade — Pays : Serbie — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 114605.0 €

Due to sensory loss diabetic patients are prone to falls and to foot ulcers, which consequently increase the risk of amputations. Because of the lack of sensory feedback amputees experience falls, perceive the prosthesis as a foreign body and therefore do not rely on it during walking. This causes counterbalancing movements that increase fatigue. Both types of patients suffer neuropathic pain, associable to aberrant sensory inputs. Neural pathways between the periphery and the brain are still functional above the damage or the amputation. Targeting these structures with peripheral neural interfaces could allow the restoration of natural sensory functionalities. The aim of project is to develop the first neuroprosthesis restoring natural foot sensations, through sciatic nerve stimulation, to patients with diabetic neuropathy or leg amputation. To that aim we will develop a detailed computational model of the sensory loop of the sciatic nerve. It will merge the electrical stimulation effects on sensory fibers and transduction of mechanical deformations of the skin into action potentials. Modelling results will be validated. Applying this modeling framework we will optimize the geometry of a peripheral neural interface, its surgical placement and define stimulation protocols that mimic natural sensory feedback responses. Effective device for feedback restoration will be constructed, able to translate the signals recorded by sensorized sole placed under the prosthetic or diabetic foot into the natural foot sensations perceived by subject. The interventional tools for embodiment boosting and pain relief will be developed. Clinical tests on amputee and diabetic subjects will assess the efficacy of the FeelAgain conceptual and technological framework by examination of pain, embodiment, ulcer prevention, falls avoidance and walking ability.

Mots-clés : neural stimulation,computational modeling,sensory feedback,neuroprosthetics
Projet ERC : CELL HORMONE (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499616.0 €

During an organism’s development it must integrate internal and external information. An example in plants, whose development stretches across their lifetime, is the coordination between environmental stimuli and endogenous cues on regulating the key hormone gibberellin (GA). The present challenge is to understand how these diverse signals influence GA levels and how GA signalling leads to diverse GA responses. This challenge is deepened by a fundamental problem in hormone research: the specific responses directed by a given hormone often depend on the cell-type, timing, and amount of hormone accumulation, but hormone concentrations are most often assessed at the organism or tissue level. Our approach, based on a novel optogenetic biosensor, GA Perception Sensor 1 (GPS1), brings the goal of high-resolution quantification of GA in vivo within reach. In plants expressing GPS1, we observe gradients of GA in elongating root and shoot tissues. We now aim to understand how a series of independently tunable enzymatic and transport activities combine to articulate the GA gradients that we observe. We further aim to discover the mechanisms by which endogenous and environmental signals regulate these GA enzymes and transporters. Finally, we aim to understand how one of these signals, light, regulates GA patterns to influence dynamic cell growth and organ behavior. Our overarching goal is a systems level understanding of the signal integration upstream and growth programming downstream of GA. The groundbreaking aspect of this proposal is our focus at the cellular level, and we are uniquely positioned to carry out our multidisciplinary aims involving biosensor engineering, innovative imaging, and multiscale modelling. We anticipate that the discoveries stemming from this project will provide the detailed understanding necessary to make strategic interventions into GA dynamic patterning in crop plants for specific improvements in growth, development, and environmental responses.

Mots-clés : systems biology of cellular hormone patterning
Projet ERC : XPRESS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Collège de France — Pays : France — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 262987.18 €

During mammalian development, precise gene expression patterns have to be established and then maintained, or reversed, in different cellular and tissue contexts. A striking example of such developmentally regulated gene control is X-chromosome inactivation (XCI), whereby one of the two X chromosomes in females is silenced during embryogenesis. XCI is initiated by the non-coding Xist RNA, which coats the chromosome in cis, triggering gene repression, chromatin changes and chromosomal reorganisation. Although Xist’s regulation has been investigated intensively, less is known about the actual mechanisms underlying the process of chromosome-wide gene silencing that it induces. Indeed, X-linked loci show very different kinetics of repression during development, implying regional and/or locus specific diversity. Furthermore, some genes avoid or escape XCI altogether, either constitutively or in a tissue or stage-specific fashion, but the molecular basis for this is unclear. Here we propose to dissect the mechanisms underlying gene regulation during XCI. We will investigate the roles of recently identified Xist partners in gene silencing and perform genetic screens to identify new factors involved in silencing and escape from XCI. Transcription, chromatin status and chromosome conformation during XCI will be investigated in an allelic-specific manner during precise developmental time windows to pinpoint the critical changes accompanying silencing and escape. We will use genetic engineering to alter genomic and epigenomic landscapes of selected loci and target candidate trans-acting factors to their putative regulatory elements. Finally, we will develop tools to explore gene expression during XCI using live cell imaging of embryogenesis. Using this innovative set of approaches, we hope to define both general principles underlying gene silencing and escape in XCI, as well as locus-specific features that could serve as new paradigms for research in developmental epigenetics.

Mots-clés : x inactivation,epigenetics,gene regulation