Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CANCER INVASION (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Princess Máxima Center — Pays : Pays-Bas — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Introduction: The ability of a cancer cell to invade into the surrounding tissue is the main feature of malignant cancer progression. Diffuse Intrinsic Pontine Glioma (DIPG) is a paediatric high-grade brain tumour with no chance of survival due to its highly invasive nature. Goal: By combining state-of-the-art imaging and transcriptomics, we aim to identify and target the key mechanisms driving the highly invasive growth of DIPG. Technology advances: Two unique single cell resolution imaging techniques that we have recently developed will be implemented: Large-scale Single-cell Resolution 3D imaging (LSR-3D) that allows visualization of complete tumour specimens and intravital microscopy using a cranial imaging window that allows imaging of tumour cell behaviour in living mice. In addition, we will apply a technique of live imaging Patch-seq to perform behaviour studies together with single cell RNA profiling. Expected results: Using a glioma murine model in which the disease is induced in neonates and a new embryonic model based on in utero electroporation, we expect to gain knowledge on the progression of DIPG in maturing brain. LSR-3D imaging on human and murine specimens will provide insight into the cellular tumour composition and its integration in the neuroglial network. With intravital imaging, we will characterize invasive cancer cell behaviour and functional connections with healthy brain cells. In combination with Patch-seq, we will identify transcriptional program(s) specific to invasive behaviour. Altogether, we expect to identify novel key players in cancer invasion and assess their potential to prevent DIPG progression. Future perspective: With the studies proposed, we will gain fundamental insights into the cancer cell invasion mechanisms that govern DIPG which may provide new potential therapeutic target(s) for this dismal disease. Overall, the knowledge and advanced technologies obtained here will be of great value for the tumour biology field.
Projet ERC : MinorSplice (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : European Molecular Biology Laboratory — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1479277.0 €

Introns are non-coding segment of eukaryotic genes, which are removed from precursors of messenger RNAs (pre-mRNAs) by a large and dynamic RNA-protein complex known as the spliceosome. In human cells, most of the introns are processed by the canonical U2-dependent, major spliceosome. Around 0.5% of human introns utilise an alternative splicing pathway, catalysed by the minor spliceosome, which depends on the U12 small nuclear RNA (snRNA). While U12-dependent introns are rare, often they are located in genes with critical cellular functions and mutations in the minor spliceosome components lead to several genetic disorders. MinorSplice project aims to perform a comprehensive structural and functional characterization of the U12-dependent splicing pathway. The functional studies will be focused on the proteomic characterization of the minor spliceosome assembly intermediates and the involvement of the conserved spliceosomal RNA helicases in the U12-dependent splicing pathway. By combining cell-based assays, proteomics and next generation sequencing methods we will create a detailed picture of the minor spliceosome composition and associated regulatory mechanisms. The core of the projects aims to determine a series of minor spliceosome’s structures using single particle electron cryo microscopy (cryo-EM). We expect that high-resolution structural information will answer some of the fundamental mechanistic questions about the minor spliceosome assembly, U12-dependent intron recognition and will shed a light on structural similarities and differences between the major and minor splicing pathways. The last part of the project will aim to visualise spliceosomes in the native cellular environment using electron cryo tomography (cryo-ET). By doing so, we anticipate to obtain functional insights into the coupling between different nuclear processes.

Mots-clés : pre mrna splicing,minor spliceosome,snrnp,helicase,cryo em
Projet ERC : MetaPG (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Trento — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499482.0 €

Investigating symbiotic gut microbes with large-scale comparative genomics would allow gaining crucial insights into the “epidemiology”, genetic diversity, and population structure of hundreds of scarcely characterized microorganisms. However, cultivation-based approaches are ineffective at targeting the large fraction of the gut microbial diversity that is hard be grown in vitro. They are also expensive and time consuming, as they need sampling specific bacteria from geographically separated subjects. On the other hand, cultivation-free metagenomic data is now available for thousands of stool samples collected worldwide, but they are not currently exploited for strain-level microbial population genomics because of the lack of suitable computational methods. In Aim1, we leverage our expertise in computational biology to bridge the gap between the fields of metagenomics and population genomics by developing novel and highly innovative methodologies to extract strain-level genomic and genetic profiles from metagenomic samples with the resolution needed by comparative genomics. Such paradigmatic shift will put us in the position of reusing in Aim2 the thousands of available metagenomes and unravel for the first time the population structure of hundreds of uncultivable gut microbes. Among the novel tasks enabled, we will focus in Aim3 on identifying those microbial strains that are currently disappearing in westernized populations as a consequence of urbanization, industrialization, high-fat diets. We will complement the available data with gut metagenomes from novel targeted cohorts of both westernized and non-westernized populations. Our project defines the foundation for cultivation-free strain-level population genomics, provides comparative genomics results with unprecedented resolution for hundreds of under-investigated microbes, and compiles a catalogue of strains undergoing or at risk of primary, secondary, or ecological extinction in westernized populations.

Mots-clés : computational metagenomics,microbial population genomics
Projet ERC : CVI_ADAPT (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1609375.0 €

Islands have played a pivotal role in evolutionary theory since Darwin and Wallace. Due to their isolation, they represent natural laboratories, providing uncomplicated microcosms where fundamental principles of the evolutionary process can be revealed. One area where island systems can provide a crucial advance is in evolutionary genetics. Here, a primary goal is to reconstruct the mechanisms, mode and tempo of the evolutionary process by identifying specific adaptive functional variants and studying the historical dynamics of these in nature. However, even with recent advances in tools and technologies (e.g., affordable genome-wide sequencing, developments in genome manipulation), the complexity of most natural systems makes this a challenging task. The proposed research launches a program that employs a unique set of thale cress (Arabidopsis) samples from intriguing populations at the edge of the species range (Cape Verde Islands) to comprehensively characterize the adaptive process in a tractable and ecologically relevant island system. This collection represents the first population sample from this region, where a single individual was collected 30 years ago and has long been an enigma due to its remarkable phenotypic and genetic divergence. We will combine field monitoring, population genetic analyses, trait mapping, powerful new genome editing technology (CRISPR), and spatially explicit modeling to reconstruct the history of the adaptive process in exceptional detail. Moreover, synthesizing our results in the context of biological networks will provide the opportunity to decipher how epistasis and pleiotropy impacted adaptive trajectories. By applying the wealth of tools available in Arabidopsis thaliana to this intriguing natural population, we will uncover general principles of adaptation and produce a roadmap and toolkit for future research in diverse systems to predict outcomes of environmental fluctuations and longer-term changes.

Mots-clés : adaptation,population genetics,arabidopsis
Projet ERC : U-HEART (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Kiel University — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : CAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Isolated dc/dc converters are increasingly employed as key components in data center, aerospace and electrical distribution, because of their capability to guarantee controllability and improve system efficiency despite power electronics is still more prone to failure with respect to other components of such systems. Fault-tolerant operation, when needed, is typically achieved through redundancy, which entails higher costs. The goal of U-HEART is to obtain fault-tolerant operation of the isolated dc/dc converter avoiding redundancy. This will lead to larger acceptance in industry, typically very skeptical when it comes to higher costs. In 2017 we have applied for a patent covering isolated dc/dc converters based on a multi-winding transformer, which can ride-through failures by means of the reconfigurability of the system and of the self-healing capacity of the cells. The hardware is reconfigurable because a part of the magnetic core with the associated winding and associated power module can be removed and self-healing because in case of a failure, the healthy part of the system realizes a different power converter function. The software will guarantee that the resulting dc/dc converter will be able to operate with one cell less or with its reconfigured version. The goal is that after a failure the overall system maintains the original functionality.

Mots-clés : power electronics,reliability
Projet ERC : DNA4Science (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Isolating genetic markers associated with phenotypes (i.e., diseases and behaviour) is one of the most promising frontiers of scientific discovery. Genetics plays a key role in understanding multiple diseases, holding a promise for medical interventions and drug targets. Attention to genotype measurement has resulted in a neglect of novel and precision phenotypes and novel measurement of other individual and environmental characteristics. Although combined genotype-phenIsolating genetic markers associated with phenotypes (i.e., diseases and behaviour) is one of the most promising frontiers of scientific discovery. Genetics plays a key role in understanding multiple diseases, holding a promise for medical interventions and drug targets. Attention to genotype measurement has resulted in a neglect of novel and precision phenotypes and attention to the measurement of other individual and environmental characteristics. Although this data is vital for scientific discovery, the largest datasets are now held by commercial direct-to-consumer (DTC) genetics companies, with increasingly limited access to scientists. Individual citizens, however, are ‘data owners’ and can freely download and donate their DTC genetic data, digital archives and fill in surveys to DNA4Science to take back control and ensure their data is used broadly by scientists. In return they receive transparency, control and reciprocity. The aim of DNA4Science is to develop a sustainable social business enterprise to ethically distribute donated data for use by certified scientists on a cost-recovery basis. Researchers will gain access to unique and novel data including aggregated digital phenotypes, ability to add customized questionnaire modules, cost-effective data collection and professional rapid dissemination. DNA4Science has the potential to lower costs of treatments and hasten their speed to market, democratizes data ownership with the rights of citizens first and lowers the costs of data collection.

Mots-clés : citizen science,genetics,digital data
Projet ERC : ASYMMEM (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

It is a basic textbook notion that the plasma membranes of virtually all organisms display an asymmetric lipid distribution between inner and outer leaflets far removed from thermodynamic equilibrium. As a fundamental biological principle, lipid asymmetry has been linked to numerous cellular processes. However, a clear mechanistic justification for the continued existence of lipid asymmetry throughout evolution has yet to be established. We propose here that lipid asymmetry serves as a store of potential energy that is used to fuel energy-intense membrane remodelling and signalling events for instance during membrane fusion and fission. This implies that rapid, local changes of trans-membrane lipid distribution rather than a continuously maintained out-of-equilibrium situation are crucial for cellular function. Consequently, new methods for quantifying the kinetics of lipid trans-bilayer movement are required, as traditional approaches are mostly suited for analysing quasi-steady-state conditions. Addressing this need, we will develop and employ novel photochemical lipid probes and lipid biosensors to quantify localized trans-bilayer lipid movement. We will use these tools for identifying yet unknown protein components of the lipid asymmetry regulating machinery and analyse their function with regard to membrane dynamics and signalling in cell motility. Focussing on cell motility enables targeted chemical and genetic perturbations while monitoring lipid dynamics on timescales and in membrane structures that are well suited for light microscopy. Ultimately, we aim to reconstitute lipid asymmetry as a driving force for membrane remodelling in vitro. We expect that our work will break new ground in explaining one of the least understood features of the plasma membrane and pave the way for a new, dynamic membrane model. Since the plasma membrane serves as the major signalling hub, this will have impact in almost every area of the life sciences.

Mots-clés : lipid asymmetry,lipid dynamics,photochemical probes,chemical biology
Projet ERC : EDJ (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : École des hautes études en sciences sociales — Pays : France — Rôle : PI
Acronyme de l'entité : EHESS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1898950.0 €

It is a paradoxical situation that with Japan being the third modern economy and Japanese, the main Japonic language, being the 10th in the world in terms of native speakers and the most widely studied Asian language, the Japonic language family still lacks an etymological dictionary. The present research project will rectify this situation. The benefits of an etymological dictionary of Japonic are obvious: not only it will be of a great use to the specialists working on pre-modern Japan and Ryukyuan islands in various disciplines; it will have its impact on modern studies, especially on linguistic identities in East Asia. And offer a new reading of regional linguistic identities The Etymological Dictionary of the Japonic languages has never been compiled, and the time for the realization of such a project is ripe, as it would have been impossible to carry on 30 or 40 years ago, since many important resources available now did not yet exist then such as numerous dictionaries and descriptions of dialects and historical stages of the language development. The same is true regarding the editions of many textual sources and compilation of their indexes. One very important difference with the previous era is also the fact that nowadays many sources are available electronically, which greatly facilitates the search and management of information. This project is highly innovative because it provides a presentation in context based on the extensive use of the IT technology, as compared to the previous research on Japonic etymology which was essentially word-list-oriented. In contrast with the current practice, where only word entries with their translations were provided (and often without any reference to the source), thanks to internet link to database, and cross-referenced entries, the electronic etymological dictionary will present the words in their textual historical and cultural context.

Mots-clés : etymology,japonic,japanese,ryukyuan,ainu,middle and old korean,middle and old,chinese,comparative method
Projet ERC : CountIce (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Leeds — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

It is becoming increasingly clear that a class of atmospheric aerosol particles which catalyse ice formation have a profound impact on clouds, precipitation and climate. For example, recent research demonstrates that massive cloud systems the size of Western Europe are almost completely removed by sufficient ice nucleating particles. However, the global distribution of ice nucleating particles is extremely poorly characterised, in part due to the lack of instrumentation which can be used for the autonomous quantification of these important particles. In my ERC Consolidator grant (MarineIce) we have developed the first instrument to automatically measure atmospheric ice nucleating particles: the Portable expansion chamber for Ice Nucleating particle mEasurements (PINE). PINE allows the repeated formation of an artificial cloud and counting of resulting ice crystals which allows us to derive the ice nucleating particle concentration. The overarching goal of CountIce is to demonstrate that the PINE chamber can indeed be used to quantify the ice nucleating particle concentration in the atmosphere while being autonomous, easy to use, have high sensitivity and low background counts, have a high time resolution, and work over a wide range of temperatures (relevant to the full spectrum of clouds that form in the Earth’s atmosphere). CountIce will therefore create value in PINE, allowing us to take the necessary steps towards commercial products which will be aimed at i) the atmospheric research community; ii) the cloud seeding community and the iii) the global atmospheric monitoring networks. CountIce will give my team the time and resources needed to adapt and develop PINE into an instrument which meets the needs of paying customers, provide the demonstration of its use in an atmospheric observatory, produce technical marketing materials, assess significant markets and develop an evidence based business plan.

Mots-clés : ice nucleating particles,cloud,cloud glaciation
Projet ERC : SIROCCO (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1798454.0 €

It is becoming increasingly clear that successful tissue engineering rests on capitalizing on more comprehensive understanding of mechanotransduction and its implication in skin homeostasis. In fact, the study of mechanotransduction is now a burgeoning research field, helping us to understand how cells respond to mechanical stimuli and convert them into biochemical signals, which in turn sheds light on the remote control of intracellular functions and the treatment of diseases. However, external activation of cellular signalling constitutes an important challenge due to the lack of non-invasive techniques that can be tuned in a spatiotemporal manner at a deep-tissue level. SIROCCO aims to control different pathways related with cutaneous mechanotransduction by using magnetic switchers in order to enhance wound healing. Magnetic nanoparticles functionalized with oriented fragments of proteins will selectively recognize cell surface adhesion receptors (cadherins) present on the membrane of living cells. Once attached to the cellular surface, the MNPs will be activated using external magnetic fields in order to control key intracellular pathways. This ambitious goal will be validated using genetically modified 2D and 3D in vitro models, and the possibility to enhance wound healing and to modulate stem cell fate will be tested. High precision remote control of cellular functions with temporal resolution is an extremely hot topic in tissue engineering. SIROCCO will go well beyond current state-of-the-art for non-invasive actuation of cellular functions in situ and will provide a powerful magnetomechanical transduction tool for mechanotransduction and tissue regeneration. The fundamental scientific advances proposed by SIROCCO are cross-disciplinary since these magnetic nanoswitchers may also find widespread applications in other processes where these pathways are involved, for instance in tumour progression.

Mots-clés : mechanotransduction,cadherin,magnetic nanoparticle,intracellular pathway