Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : BYPASSWITHOUTSURGERY (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 1911072.36 €

Gastric bypass surgery results in massive weight loss and diabetes remission. The effect is superior to intensive medical treatment, showing that there are mechanisms within the body that can cure diabetes and obesity. Revealing the nature of these mechanisms could lead to new, cost-efficient, similarly effective, non-invasive treatments of these conditions. The hypothesis is that hyper-secretion of a number of gut hormones mediates the effect of surgery, as indicated by a series of our recent studies, demonstrating that hypersecretion of GLP-1, a hormone discovered in my laboratory and basis for the antidiabetic medication of millions of patients, is essential for the improved insulin secretion and glucose tolerance. But what are the mechanisms behind the up to 30-fold elevations in secretion of these hormones following surgery? Constantly with a translational scope, all elements involved in these responses will be addressed in this project, from detailed analysis of food items responsible for hormone secretion, to identification of the responsible regions of the gut, and to the molecular mechanisms leading to hypersecretion. Novel approaches for studies of human gut hormone secreting cells, including specific expression analysis, are combined with our advanced and unique isolated perfused gut preparations, the only tool that can provide physiologically relevant results with a translational potential regarding regulation of hormone secretion in the gut. This will lead to further groundbreaking experimental attempts to mimic and engage the identified mechanisms, creating similar hypersecretion and obtaining similar improvements as the operations in patients with obesity and diabetes. Based on our profound knowledge of gut hormone biology accumulated through decades of intensive and successful research and our successful elucidation of the antidiabetic actions of gastric bypass surgery, we are in a unique position to reach this ambitious goal.

Mots-clés : gut hormones,incretin hormones,glp 1,gastric bypass,diabetes,obesity,enteroendocrine cells
Projet ERC : Sphingolead (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Gaucher disease (GD) is an autosomal recessive disorder caused by deficient activity of acid glucosylceramidase (GBA1). Most patients feature a non-neuronopathic (type 1) course of disease and are treated by either enzyme replacement therapy (ERT – administration of recombinant GBA1) or substrate reduction therapy (SRT – treatment with the iminosugar, Zavesca or the ceramide mimic, Eliglustat – inhibitors of glucosylceramide synthase (GCS)). These therapeutic agents do not prevent neurological symptoms in patients suffering from neuronopathic Gaucher forms (types 2/3) and there is thus an unmet medical need for these patients. Potent GCS inhibitors reduce glucosylceramide (GlcCer), the substrate of GBA and the storage material in Gaucher, and also higher glycosphingolipids including gangliosides and globosides, the causative storage materials in Tay-Sachs disease, GM1 gangliosidosis and Fabry disease. We have found a highly attractive lead, BiPheDNM 7 (Figure C below), which we plan to further develop towards a phase I/II clinical candidate. This proof of concept project will result in a packet comprising this lead molecule, accompanied by all the relevant data and tools to start phase I/II clinical development together with a pharmaceutical partner.

Mots-clés : glucosylceramide synthase,gaucher disease,gba1,gcs inhibitors
Projet ERC : LaGaTYb (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498980.0 €

Gauge theories establish a connection between seemingly different physical areas, ranging from high-energy to condensed matter physics and topological quantum computing. Very often gauge theories are difficult to study theoretically in particular in the strongly-interacting regime, where perturbative methods are not reliable. Despite the remarkable progress offered by numerical methods, such as classical Monte Carlo simulations, the sign problem imposes severe limitations, for instance, regarding real-time dynamics. This motivates the search for alternative approaches. Recent progress in the control of engineered quantum systems has revitalized Feynmans's idea of quantum simulation, which naturally does not suffer from the sign problem because its working principle is quantum mechanical. Ultracold atoms in optical lattices have proven powerful in studying important condensed matter models and intriguing results have been achieved in simulating static background gauge fields. This establishes a link to more general gauge theories, yet these are out-of-reach due to complex requirements e.g. regarding the implementation of gauge and matter field degrees of freedom. Achieving significant progress in this direction requires a radically new approach. I propose to develop a novel experimental platform that combines two unique features: precise local control as typical for ion traps and scalability of cold-atom setups to generate advanced optical lattices with locally controllable tunnel couplings. It will facilitate the implementation of a broad class of gauge theories, so-called quantum link models, with fermionic atoms, where matter and gauge fields are interpreted as different lattice sites. The proposed model exhibits paradigmatic phenomena of quantum electrodynamics and doped Mott insulators in connection to high temperature superconductors and provides a roadmap to study more complex non-Abelian models based on the nuclear spin states of Alkaline-earth-like atoms.

Mots-clés : quantum simulation,lattice gauge theories,quantum link models
Projet ERC : RetroNets (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
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 : 1993858.0 €

Gene regulatory networks (GRNs) are an important cellular signal processing mechanism for translating input signals into appropriate phenotypes by modulating expression of the genome. The quantitative details of how cells process information through GRNs are still poorly understood, but of central importance in a large number of biological processes. Considerable progress has been made in mapping the topology of GRNs and more recently in deciphering the relationship between promoter sequence and function. Nonetheless, it is not yet possible to computationally predict the output of most native promoters, nor is it trivial to build promoters that integrate signals in a novel and predictive manner. Developing a quantitative understanding of transcriptional regulation, ultimately leading to the ability to predict entire GRNs will be a significant achievement and a prerequisite for our ability to engineer biological systems. I propose a multi-disciplinary approach incorporating biology, engineering, and computational modelling to improve our quantitative understanding by reverse engineering GRNs in S. cerevisiae. My research group has developed a powerful set of unique, high-throughput microfluidic technologies that enable the quantitative analysis of GRNs in vitro and in vivo. Specifically I propose to quantitatively investigate the yeast phosphate regulatory network and to develop a master model capable of predicting output of the network under various inorganic phosphate concentrations, to develop novel approaches for modulating GRNs using engineered Zn-finger transcription factors (TF) and CRISPR/Cas, to link GRN output to fitness in order to develop an understanding of how networks are optimized and evolve, and to reverse engineer an exact functional copy of the native phosphate regulatory network with orthogonal components.
Projet ERC : TeraSHAPE (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Karlsruhe Institute of Technology — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : KIT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2498954.0 €

Generation, detection, and processing of electromagnetic waveforms is one the most important tech-nical foundations of modern society. Digital signal processing, in particular, has revolutionized many areas of science and engineering. By exploiting massively parallel processing with tens of billions of transistors at comparatively low internal clock speed, CMOS circuits can provide output data rates of hundreds of gigabit per second, corresponding to effective clock rates of several hundred GHz. In contrast to that, the analog bandwidth of electronic circuits is much more difficult to scale due to limited switching speed of semiconductor devices, strongly increased transmission line losses at high frequencies, and the considerable complexity associated with high-speed circuit packaging and as-sembly. TeraSHAPE aims at overcoming these limitations by establishing the foundations of novel signal processing concepts at T-wave frequencies between 100 GHz and 1 THz. Capitalizing on cutting-edge results in the fields of photonic integration and optical frequency comb generation, TeraSHAPE will combine massively parallel processing in digital electronic circuits with synthesis and analysis of broadband waveforms in the optical domain. To convert waveforms between optical and T-wave frequencies, TeraSHAPE will explore novel concepts for ultra-fast devices such as silicon-organic hybrid electro-optic modulators and silicon-plasmonic photodetectors with bandwidths of hundreds of GHz. Advances on the device level will be complemented by scalable assembly concepts, where TeraSHAPE will exploit 3D printing on the micro- and nanoscale both for hybrid photonic integration and for realizing sub-mm THz waveguides. The viability of the TeraSHAPE concepts will be experimentally demonstrated in applications of high relevance such as high-speed wireless communications at data rates of up to 1 Tbit/s or signal processing in high-field electron paramagnetic resonance (EPR) spectroscopy.

Mots-clés : integrated photonics,plasmonics,terahertz technology
Projet ERC : PUNCTUATION (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
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 : 1499952.0 €

Genomic DNA represents the blueprint of life: it instructs solutions to challenges during life cycles of organisms. Curiously DNA in higher organisms is mostly non-protein coding (e.g. 97% in human). The popular “junk-DNA” hypothesis postulates that this non-coding DNA is non-functional. However, high-throughput transcriptomics indicates that this may be an over-simplification as most non-coding DNA is transcribed. This pervasive transcription yields two molecular events that may be functional: 1.) resulting long non-coding RNA (lncRNA) molecules, and 2.) the act of pervasive transcription itself. Whereas lncRNA sequences and functions differ on a case-by-case basis, RNA polymerase II (Pol II) transcribes most lncRNA. Pol II activity leaves molecular marks that specify transcription stages. The profiles of stage-specific activities instruct separation and fidelity of transcription units (genomic punctuation). Pervasive transcription affects genomic punctuation: upstream lncRNA transcription over gene promoters can repress downstream gene expression, also referred to as tandem Transcriptional Interference (tTI). Even though tTI was first reported decades ago a systematic characterization of tTI is lacking. Guided by my expertise in lncRNA transcription I recently identified the genetic material to dissect tTI in plants as an independent group leader. My planned research promises to reveal the genetic architecture and the molecular hallmarks defining tTI in higher organisms. Environmental lncRNA transcription variability may trigger tTI to promote organismal responses to changing conditions. We will address the roles of tTI in plant cold response to test this hypothesis. I anticipate our findings to inform on the fraction of pervasive transcription engaging in tTI. My proposal promises to advance our understanding of genomes by reconciling how the transcription of variable non-coding DNA sequences can elicit equivalent functions.

Mots-clés : long non coding rna,lncrna,rna polymerase ii,transcriptional interference,co transcriptional control,the non coding genome,pant biology
Projet ERC : TENSION (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University Medical Center Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMCG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1972500.0 €

Genomic instability characterizes tumors, which have no clear ‘oncogenic-driver’ mutation, including triple-negative breast cancers (TNBCs). These patients do not benefit from molecularly targeted treatment and urgently need better treatment options. Increasing evidence points to replication stress as the driver of genomic instability. Since replication stress compromises cell viability, cells have evolved mechanisms to mitigate this threat. Recently, I discovered a novel cellular mechanism—mitotic Replication Stress Recovery (RSR)—that acts as an ‘emergency brake’ during mitosis, allowing recovery from high levels of replication stress. This machinery is critical for tumor cell survival, and therefore constitutes a promising target for anti-cancer drug development. However, it is unclear how this mitotic RSR is organized molecularly and how it can be targeted therapeutically. In this project, I aim to molecularly define and therapeutically target the Mitotic Replication Stress Recovery (RSR) machinery in triple-negative breast cancer cells. To this end, I will implement a series of complementary innovative strategies. First, I will use mass-spec-based proteomics to molecularly characterize components and wiring of the mitotic RSR machinery. Second, to identify the genetic profiles of cancer subgroups that are sensitive to inactivation of the mitotic RSR, functional genetic screens will be combined with visualization and quantification of replication stress in genomically-defined human cancer samples. Finally, my findings will be translated to the pre-clinical situation by exploring the feasibility of therapeutic inactivation of the RSR machinery in vitro and in vivo in a panel of triple-negative breast cancer models. In summary, TENSION will provide advanced insight into the composition and wiring of the mitotic RSR machinery and will reveal the potency of targeting this pathway therapeutically for TNBCs and other hard-to-treat, genomically instable cancers.

Mots-clés : breast cancer,mitosis,dna repair,genomic instability
Projet ERC : GENIE (Horizon 2020, appel 2020, Synergy grants)
Entité participante : International Institute for Applied Systems Analysis — Pays : Autriche — Rôle : PI
Acronyme de l'entité : IIASA
Type d'entité : Recherche
Financement ERC de l'entité : 2846494.0 €

Geoengineering technologies, such as solar radiation management (SRM), and negative emissions technologies, such as greenhouse gas removal (GGR), are emerging options to address climate change. This project will investigate the environmental, technical, social, legal, and policy dimensions of GGR and SRM. We provide an urgently needed interdisciplinary and holistic perspective of these technologies in order to understand conditions under which they might be deployed at scale. Our meta-analytical framework integrates insights from social science, engineering and physical science disciplines to provide a comprehensive view of GGR and SRM in the transition to climate neutrality in Europe and the world. The project will conduct excellent research and generate a robust, scientific assessment for evidence-based policymaking. Our research framework consists of three pillars—techno-economic systems, socio-technical systems, and systems of political action—within which we place six work packages (WPs). These are: (1) Understanding the current state and future potential of GGR and SRM technologies in terms of their technical and economic features; (2) Analysing bottlenecks in transitions to climate neutrality and their implications for deployment; (3) Identifying social acceptance and legitimacy constraints, (4) Learning, diffusion, and adoption; (5) Implications for Sustainable Development Goals of archetypical mitigation pathways; and 6) Policy options and governance. A crosscutting WP7 synthesizes research along three salient, but under-researched themes: A) Socio-technical change; B) Managing transition risks; and C) Political economy and feasibility of deployment. WP8 focuses on stakeholder engagement, entailing scenario co-design, science-policy dialogue formats, and specific outreach formats for target groups.

Mots-clés : negative emissions,geo engineering,solar radiation management,carbon dioxide removal,climate policy,energy policy
Projet ERC : ENFORCE (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : University of Barcelona — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1850298.0 €

Geometric frustration, namely the impossibility of satisfying competing interactions on a lattice, has recently become a topic of considerable interest as it engenders emergent, fundamentally new phenomena and holds the exciting promise of delivering a new class of nanoscale devices based on the motion of magnetic charges. With ENFORCE, I propose to realize two and three dimensional artificial colloidal ices and investigate the fascinating manybody physics of geometric frustration in these mesoscopic structures. I will use these soft matter systems to engineer novel frustrated states through independent control of the single particle positions, lattice topology and collective magnetic coupling. The three project work packages (WPs) will present increasing levels of complexity, challenge and ambition: (i) In WP1, I will demonstrate a way to restore the residual entropy in the square ice, a fundamental longstanding problem in the field. Furthermore, I will miniaturize the square and the honeycomb geometries and investigate the dynamics of thermally excited topological defects and the formation of grain boundaries. (ii) In WP2, I will decimate both lattices and realize mixed coordination geometries, where the similarity between the colloidal and spin ice systems breaks down. I will then develop a novel annealing protocol based on the simultaneous system visualization and magnetic actuation control. (iii) In WP3, I will realize a three dimensional artificial colloidal ice, in which interacting ferromagnetic inclusions will be located in the voids of an inverse opal, and arranged to form the FCC or the pyrochlore lattices. External fields will be used to align, bias and stir these magnetic inclusions while monitoring in situ their orientation and dynamics via laser scanning confocal microscopy. ENFORCE will exploit the accessible time and length scales of the colloidal ice to shed new light on the exciting and interdisciplinary field of geometric frustration.

Mots-clés : geometric frustration,soft matter,colloids,magnetism,artificial spin ice
Projet ERC : MMiMMa (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : University of Glasgow — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1889131.0 €

Geometrically, this proposal is concerned primarily with Calabi--Yau threefolds, their (local) classification, their homological properties, various associated structures such as stability conditions and Frobenius manifolds, and the resulting predictions across mirror symmetry. Our approach to these problems is through noncommutative algebra, and necessarily so. We will use techniques from contraction algebras and noncommutative resolutions to classify, using both theoretical and constructive methods, and in the process verify an amended version of a string theory prediction. We will use this to push forward curve-counting and derived category consequences and obstructions, and will work towards building a full database of 3-fold flops. On a parallel track, we will treat fundamental problems in noncommutative resolutions and their variants, and approach some of the founding conjectures in the area. We will tackle problems such as existence of MMAs through to more specific problems such as faithful actions and K(pi,1) through stability manifolds and tilting theory on preprojective algebras. We will furthermore merge all this into an emerging theory of Frobenius manifolds, SKMS, and schobers, and through this expand on recent work constructing mirrors to various flopping contractions.

Mots-clés : noncommutative resolutions,contractions,stability conditions,finite dimensional algebras