Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PanCaT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2440275.0 €

Maintenance and drug resistance of pancreatic ductal adenocarcioma (PDAC) depends on cancer cell intrinsic mechanisms and a stroma that supports tumor growth. Mouse models of human PDAC have provided important insights into the evolution of this highly lethal tumor, but there are no models that allow secondary genetic manipulation of autochthonous tumors, the tumor microenvironment or the metastatic host niche once the tumor has formed. We generated an inducible dual-recombinase system by combining Flp/frt and Cre/loxP. This novel PDAC model permits spatial and temporal control of gene expression enabling unbiased genetic approaches to study the role of tumor cell-autonomous and non-autonomous functions in endogenous cancers. This tool provides unparalleled access to the native biology of cancer cells and their hosting stroma, and rigorous genetic validation of candidate therapeutic targets. We performed tumor cell-autonomous and non-autonomous targeting, uncovered hallmarks of human multistep carcinogenesis, validated genetic tumor therapy, and showed that mast cells in the tumor microenvironment, which had been thought to be key oncogenic players, are in fact dispensable for tumor formation. In the proposed research program, we will 1) develop and further improve next-generation PDAC models, 2) deploy these systems to identify and target key features of PDAC maintenance in tumor cells and their microenvironment, and 3) discover mechanisms of treatment resistance. The application of cutting edge genetic engineering and screening technologies will allow us to address biological questions that could not be addressed before. The PanCaT project will open new horizons for the functional understanding of pancreatic cancer biology with a strong impact on clinical management and prognosis of PDAC patients. It will also produce a unique set of highly versatile and widely applicable genetic tools that will facilitate the study of PDAC at an organismal level.

Mots-clés : genetically engineered mouse models,loxp system,transposon mutagenesis,gene targeting,tumor progression and maintenance,3 phosphoinositide dependent protein kinase,pdpk1  pdk1,kras signaling
Projet ERC : LearnAnx_CircAmyg (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1981175.0 €

Major advances were made in understanding circuits that underlie aversive emotional learning. The majority gained by using classical associative models, mainly tone/context-shock conditioning. Failure to extinguish the response or to discriminate from other safe stimuli (generalization), form two main animal models for human anxiety-disorders and post-traumatic-stress. These simple yet powerful approaches enabled cutting-edge techniques in rodents to unveil amygdala circuitry and its connectivity with the medial-prefrontal-cortex. Yet, we have less understanding of the mechanisms that underlie elaborated behavioural models of mal-adaptive behaviour, as well as less understanding of neural codes and computations in the evolutionary-expanded primate amygdala. Our lab recently embarked on exploring these venues by pioneering physiological studies of generalization and extinction protocols in primates. The goal of the current project is to develop behavioural models of complex learning and maladaptive behaviour, and then examine and shed light on the underlying computations in primate amygdala-PFC circuit. We design a novel rule-based learning task, and examine its acquisition, extinction, generalization and exploration-exploitation trade-off in dangerous environments. Specifically, the concepts of rule learning and exploration-exploitation tradeoff form novel insights and aspects of [mal-]adaptive behaviours, and will suggest new animal models of learned anxiety. We record dozens of neurons in the amygdala and prefrontal-cortex simultaneously using deep multi-contact arrays, supplemented by stimulation to address functional connectivity, and development of modelling approaches for the behaviour and neural codes. We posit that the development of more [complex] models is crucial and the next logical step in achieving translation of animal models of anxiety disorders, as well as in understanding basic mechanisms behind the rich repertoire of emotional behaviours.

Mots-clés : amygdala,aversive learning,anterior cingulate cortex,anxiety disorders,electrophysiology,safety
Projet ERC : XChromosome (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1912369.0 €

Male and female mammals differ in their sex chromosome complement: males have one X chromosome and one Y chromosome (XY), while females have two X chromosomes (XX). Decades of research have demonstrated that the Y chromosome is crucial for male fertility, regulating both sex differentiation and spermatogenesis. However, the role of the X chromosome in these critical stages of germ line development remains poorly understood. In this proposal, we will explore the functions of the X chromosome in the mammalian germ line. In eutherian mammals, sex determination is dependent on the Y-gene Sry, but in the other major mammalian class, the metatherians, it is controlled not only by a Y-locus, but also by the complement of X chromosomes. In Aim 1 we will apply CRISPR-mediated genome editing to metatherian mammals in order to identify these critical X and Y sex-determining genes. Our findings will provide insight into mammalian sex chromosome evolution and the aetiology of human sex differentiation disorders. In addition to its role in sex determination, the X chromosome is also predicted to become evolutionarily specialised for spermatogenesis. Consistent with this theory, we discovered that the mouse X chromosome is enriched in genes expressed exclusively in developing sperm. These genes are present in multiple copies, and together comprise an unprecedented 18% of the mouse X chromosome gene content. Many could be important candidates for unexplained male infertility. However, the functions of these genes have not been determined, because they cannot be manipulated using conventional gene targeting strategies. In Aim 2, we will use CRISPR to establish the roles of X-multicopy genes in male reproduction.

Mots-clés : sex chromosomes,germ cell development,infertility
Projet ERC : PalM (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1418195.0 €

Mammals are ubiquitous, with over 5000 species across the globe. But how did mammals become so successful? There is vigorous debate among palaeontologists: did mammals explosively diversify after a sudden environmental crisis knocked out dinosaurs at the end of the Cretaceous (~66 million years ago) or rise to dominance more slowly, alongside the dinosaurs? The debate persists because we still know very little about those mammals that flourished during the ~10 million years after the end-Cretaceous extinction (the early Paleogene), as they are largely ignored because their ‘archaic’ anatomy has long confounded palaeontologists. This project will use a wealth of newly discovered fossils and state-of-the-art analytical techniques to finally untangle the evolutionary story of these ~200 critical species. We will comprehensively study the anatomy of ‘archaic’ species using state-of-the-art imaging technology and build a species-level genealogy placing these long-mysterious mammals in the context of their Cretaceous forebears and modern mammals. Cutting-edge quantitative methods for studying evolution, including novel techniques developed here, will be applied to the family tree to date the origin of placental mammals and the major modern groups, determine what effect the end-Cretaceous extinction had on mammalian biodiversity, quantify the tempo and mode of the placental radiation, and explicitly test for potential drivers of mammalian diversification. This will give ground-breaking insight into how major groups become successful over evolutionary time and how biodiversity is affected and reset by dramatic environmental changes, a pressing concern in today’s rapidly changing world.

Mots-clés : palaeontology,macroevolution,evolution,mass extinctions,phylogenetics,mammals
Projet ERC : Extr3Me (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499478.0 €

Manipulating physical signals such as light, sound, heat or motion is a vital challenge in multiple areas of science. Due to recent advances in digital fabrication techniques, the last years have seen a revolution in artificial periodic composites with on-demand electromagnetic, acoustic, thermal and mechanical properties. These so-called metamaterials become particularly interesting in mechanics, where geometrical effects and nonlinearities are much stronger than in any other physical field. Over the past 5 years, the community -including myself- has discovered a plethora of “extreme” functionalities, e.g. mechanical metamaterials that are very light, stiff and strong at the same time, that have negative elastic moduli or that exhibit programmable shape-changes. Importantly, such advanced properties are typically designed through a purely geometrical framework. Yet, this impressive progress is so far confined to idealized settings, namely for homogeneous boundary conditions, imperfection-free structures and purely elastic constituents under quasi-static driving. This traditional focus severely limits our understanding of metamaterials and their potential for applications. Here, I propose to uncover the extreme mechanics of metamaterials under realistic conditions. Specifically, by generalizing the geometrical framework to allow for deviations from the ideal limit, and by validating it through a wide array of experimental and numerical techniques, I will establish: 1) the effect of inhomogeneous boundary conditions; 2) the sensitivity to geometric imperfections; 3) the role of dissipation. Just as the fundamental understanding of defects and dislocations revolutionized materials science, by exploring perturbations in metamaterials I will push the frontiers of solids mechanics and open up avenues for the design of robust advanced functionalities tailored to realistic complex scenarios, from prosthetics to aerospace.

Mots-clés : metamaterials,elastic instabilities,compliant mechanisms,imperfections
Projet ERC : CO-MAN (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999975.0 €

Many control systems of the future involve a tight interaction or even symbiosis with the human user. High-impact application domains of human-centric systems include healthcare, mobility, and infrastructure systems. In human-centric systems the human is both, an element of the control system, and a design criterion with individual requirements that need to be satisfied. Safety - despite the high uncertainty of human behavior - and maximization of individual user experience are the primary objectives for control design in human-centric systems. The visionary goal of CO-MAN is to contribute to the fundamental understanding and principled approach to the control of smart human-centric systems. We will develop a novel framework for user-adaptive data-driven control with performance guarantees in order to address the scientific challenges of high uncertainty and individual user requirements. The grand challenge is to unify the two previously separate paradigms of model-based control with its rigorous guarantees but limited modeling base and machine learning algorithms with its flexible modeling concepts but lack of guarantees. The breakthrough enabling idea is to merge probabilistic non-parametric modeling techniques from statistical learning theory with novel risk-aware control methodologies while including active user modeling. The game changer is the current push towards reliable machine learning with novel results on theoretical bounds for learning behavior. Because of favorable properties we will focus on Gaussian Processes to model user behavior and preferences and translate the naturally quantified model uncertainty into closed loop behavior guarantees through a confidence-driven human-interactive control approach. The PI is in a perfect position to achieve the envisioned goal of super-individualized data-driven control with performance guarantees given the highly visible preliminary results and leadership in the area of human-cyber-physical systems.

Mots-clés : human centric control systems,human interactive data driven control
Projet ERC : ChromSpaces (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Utrecht University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Many current developments in stable homotopy theory are guided by the ‘chromatic perspective’. One decomposes a spectrum into its monochromatic pieces, each of which is a localization corresponding to one of the prime fields of higher algebra (the Morava K-theories, generalizing the prime fields Q and F_p of ordinary algebra). The goal of this proposal is to study the chromatic decomposition of spaces, as opposed to that of spectra. I will establish structural results for the category of all monochromatic spaces ‘of a given color’ and study the assembly question: how to put the pieces back together to retrieve information about the original space? The techniques are informed by my recent results relating monochromatic spaces to spectral Lie algebras, which generalize Quillen’s rational homotopy theory to all the other relevant chromatic localizations of homotopy theory. More precisely, this research has the following goals. 1. Develop the structure theory of spectral Lie algebras and apply it to monochromatic spaces. This includes understanding Koszul duality between spectral Lie algebras and commutative ring spectra, with applications to a conjecture of Francis-Gaitsgory, and decomposition results for spectral Lie algebras, with applications to torsion exponents of homotopy groups, building on classical work of Cohen-Moore-Neisendorfer. 2. Develop a theory of transchromatic spectral Lie algebras, explaining how the different monochromatic pieces of homotopy theory interact. This connects to my previous work on the Goodwillie tower of homotopy theory and Tate coalgebras.

Mots-clés : msc2010  55pxx homotopy theory,55p43 spectra with additional structure,55q51  v n  periodicity
Projet ERC : FastMat (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Arts et Métiers Sciences et Technologies — Pays : France — Rôle : Partner
Acronyme de l'entité : Arts et Métiers
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 344700.0 €

Many mechanical structures are submitted to repeated loadings and can break under stress lower than the ultimate tensile stress. This phenomenon is called the fatigue of materials and can be found in many industrial sectors, such as the transport industry, aeronautic industry and energy production. Fatigue design is thus crucial in engineering and it requires the precise characterization of material behavior under cyclic loadings to ensure the safety and reliability of structures throughout their life. An increase in the life span of a structure or a reduction in the number of maintenance phases leads to an increases in the number of cycles applied to this structure. It is presently common to find mechanical systems subjected to several billion cycles, in what is called the gigacycle fatigue domain. The characterization of the fatigue behavior of materials requires fatigue tests to be conducted until fracture for different stress amplitudes. One problem with this method is the test duration, which becomes excessive and beyond possible, particularly for a very high number of cycles. The goal of FastMat is to develop a new method that reduces considerably the duration of fatigue characterization. This method involves the use of only short interrupted tests coupled with a self-heating measurement to characterize the fatigue behavior for very low stress amplitudes. The scientific objective is to develop simultaneously experimental and numerical tools for the fast determination of fatigue behavior. The experimental approach will be developed to estimate simultaneously the dissipation and the stored energy, which directly reflect fatigue damage. For the numerical approach, discrete dislocation dynamics simulations will be developed to establish links between the fatigue damage associated with the evolution of dislocation structures, the stored energy and the dissipated energy.

Mots-clés : gigacycle fatigue
Projet ERC : KL2MG-interactions (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : University of Bonn — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1719583.0 €

Many milestone results in mathematics emerge from interactions and transfer of techniques and methods between different areas. I want to attack outstanding problems concerning K-theory, L^2-invariants, manifolds and group theory. The time is ripe to use the exciting and profound progress that has been made during the last years in the individual areas to build new bridges, gain new insights, open the door to new applications, and to trigger new innovative activities worldwide lasting beyond the proposed funding period. The starting point are the prominent conjectures of Farrell-Jones on the algebraic K- and L-theory of group rings, of Baum-Connes on the topological K-theory of reduced group C^*-algebras, and of Atiyah on the integrality of L^-Betti numbers. I intend to analyze and establish the Farrell-Jones Conjecture in other settings such as topological cyclic homology of ``group rings'' over the sphere spectrum, algebraic K-theory of Hecke algebras of totally disconnected groups, the topological K-theory of Fr'echet group algebras, and Waldhausen's A-theory of classifying spaces of groups. This has new and far-reaching consequences for automorphism groups of closed aspherical manifolds, the structure of group rings, and representation theory. Recent proofs by the PI of the Farrell-Jones Conjecture for certain classes of groups require input from homotopy theory, geometric group theory, controlled topology and flows on metric spaces, and will be transferred to the new situations. There is also a program towards a proof of the Atiyah Conjecture based on the Farrell-Jones Conjecture and ring theory. Furthermore, I want to attack open problems such as the approximation of L^2-torsion for towers of finite coverings, and the relation of the first L^2-Betti number, the cost and the rank gradient of a finitely generated group. I see a high potential for new striking applications of the Farrell-Jones Conjecture and L^2-techniques to manifolds and groups.

Mots-clés : manifolds,algebraic k  and l theory,l 2 invariants,geometric group theory
Projet ERC : Life-Inspired (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Many of the key functions typically associated with living systems, including sensing of the environment, autonomous decision making, and extracting energy and building blocks from the environment for cell growth and division, are all governed by enzymatic reaction networks. Constructing synthetic systems that capture some of these capabilities, i.e. life-inspired systems, would represent a truly disruptive development, as they challenge our notion of what differentiates living systems from synthetic, man-made devices. However, the ability create synthetic life-inspired systems remains an elusive goal. Despite impressive progress in systems chemistry, no clear engineering principles or methodologies exist for the bottom-up construction of functional complex molecular systems The translation of the design principles of living systems into programmable and functional life-inspired systems is one of the outstanding grand challenge in chemistry. The ultimate aim of this proposal is to construct life-inspired systems based on the design blueprints of living matter To achieve this aim, I propose a key breakthrough by presenting a completely new approach to functional complex systems based on programmable enzymatic reactions networks. The envisaged approach is modular and will allow for systematic increases in complexity. The core objectives of this proposal are: - establish a completely new approach to programmable enzymatic reaction networks - compartmentalize network motifs, and separate the small molecule ‘software’ from the enzyme ‘hardware’ - demonstrate modularity and increase the complexity via communication between compartments - develop robust methods to manage the maintenance of non-equilibrium conditions - design and construct complex life-inspired systems.

Mots-clés : out of equilibrium reaction networks,systems chemistry