Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SISCAN (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Lund University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 63812.0 €

The idea to be taken to proof of concept is a novel real-time characterization device for short laser pulses, based upon SIngle-Shot dispersion SCAN (SISCAN). The use of femtosecond laser pulses with duration from the single-cycle to the multi-cycle regime, in various applications in research, industry or medicine demands a precise characterization and control of each laser pulse. We propose a device for measuring the intensity and the phase of laser pulses, based upon dispersion scans, i.e. scans of the second harmonic spectrum as a function of dispersion of the fundamental field. The device is able to characterize individual laser pulses and therefore will provide useful realtime feedback to adjustments of any laser system. Recently, in the effort to improve the control of light pulses required for our ERC-supported research, two variants of a single-shot d-scan, i.e. one for few-cycle pulses (3-10 fs) and one for longer pulses (15-100 fs) were developed. At the same time, we introduced a new algorithm, drastically reducing the retrieval time. The combination of these developments will allow for measuring individual pulse properties in real-time for very diverse types of lasers. At the time this application is being sent, two patent applications have been submitted. Through technical verification (Lund University, Sweden) and business activities (a small company located in Portugal, Sphere Ultrafast Photonics, already commercializing the original, multiple shot version of the device), we will demonstrate the functionality of the concept, the risks will be assessed and minimized and we will prepare to exploit the increased commercial potential, addressing laser manufacturers as well as laser users in both the scientific and commercial spheres.

Mots-clés : ultrafast optics,ultrashort laser pulses,time frequency characterization,dispersion scan
Projet ERC : LDMThExp (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1822083.0 €

The identity of dark matter (DM) is still unknown. For more than three decades, significant theoretical and experimental efforts have been directed towards the search for a Weakly Interacting Massive Particle (WIMP), often overlooking other possibilities. The lack of an unambiguous positive signal, at indirect- and direct-detection experiments and at the LHC, stresses the need to expand on other theoretical possibilities, and more importantly, to develop new experimental capabilities. Indeed it is conceivable that the WIMP paradigm has been misleading, and other theoretically motivated scenarios must be explored vigorously. This proposal focuses on light, sub-GeV dark matter. In addition to novel theoretical paradigms that point to DM in the low-mass regime, several new strategies to directly detect dark matter particles with MeV to GeV mass, far below standard direct detection capabilities, are studied. In particular, techniques to search for ionized electrons or chemical bond-breaking are considered. The latter possibility is revolutionary and requires new dedicated technologies and experiments. Sensitivity to one or few electrons, on the other hand, has been established and the PI has recently derived the first direct-detection limits on MeV to GeV dark matter using XENON10 data, demonstrating proof-of-principle. Significant efforts are required to lay the theoretical foundation of light DM and to study in depth and develop the various possibilities to directly detect it. The proposal is centered around these efforts. The innovative theoretical paradigms and novel avenues to experimentally detect sub-GeV DM, open up a new and groundbreaking field of research. The proposal at hand takes the necessary steps, and offers the opportunity to pave the way and enable the discovery of such a particle, if it exists.
Projet ERC : IMAP (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1495000.0 €

The immune system can patrol cell status by recognising epitopes bound to Human Leukocyte Antigen class I (HLA-I) molecules and triggering cytotoxic T cell (CTL) activation. Epitopes arrive at the cell surface through several steps of the antigen processing and presentation pathway (APP). Despite major discoveries in the past decades, the precise dynamics of APP are still not fully understood. These dynamics, however, determine the types and quantities of epitopes and therefore regulate the CTL response. The objective of my project is the development of an APP model from gene transcription to recognition by CTL clones that captures the underlying APP mechanisms and dynamics. Current approaches are mainly machine learning-based and focus only on parts of the APP. They neglect the underlying APP dynamics and do not elucidate novel mechanisms. Therefore, they fail to predict epitopes under altered cellular states such as infection. My project overcomes this pitfall by complementing large scale machine learning approaches with mechanistic modelling to comprehensively understand the APP and enable successful epitope prediction. To achieve this goal, I will: 1) develop an APP integrated computational description that combines a mechanistic model of the APP (based on detailed quantitative in vitro data) with a large-scale machine learning-based multi-omics model; 2) apply the model in two therapeutic-relevant cellular systems – Measles virus infection and chemotherapy-induced senescence – resulting in the educated identification of canonical and non-canonical epitopes. This project is at the cutting edge of the research with direct application in epitope discovery for therapies such as anti-cancer immunotherapy, vaccination against infection and modulatory immunotherapies against autoimmune diseases. The implemented computational framework will be made available to the community thereby providing a direct benefit to European scientific public and private sectors.

Mots-clés : hla i antigen processing and presentation,proteasome,peptide splicing,epitope prediction,bayesian model inference
Projet ERC : BARCODED-CELLTRACING (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : German Cancer Research Center — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DKFZ
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

The immune system is a complex ensemble of diverse lineages. Studies on in-vivo-hematopoiesis have until now largely rested on transplantation. More physiological experiments have been limited by the inability to analyze hematopoietic stem (HSC) and progenitor cells in situ without cell isolation and other disruptive manipulations. We have developed mouse mutants in which a fluorescent marker can be switched on in HSC in situ (inducible fate mapping), and traced HSC lineage output under unperturbed conditions in vivo. These experiments uncovered marked differences comparing in situ and post-transplantation hematopoiesis. These new developments raise several important questions, notably on the developmental fates HSC realize in vivo (as opposed to their experimental potential), and on the structure (routes and nodes) of hematopoiesis from HSC to peripheral blood and immune lineages. Answers to these questions (and in fact the deconvolution of any tissue) require the development of non-invasive, high resolution barcoding systems. We have now designed, built and tested a DNA-based barcoding system, termed Polylox, that is based on an artificial recombination locus in which Cre recombinase can generate several hundred thousand genetic tags in mice. We chose the Cre-loxP system to link high resolution barcoding (i.e. the ability to barcode single cells and to fate map their progeny) to the zoo of tissue- or stage-specific, inducible Cre-driver mice. Here, I will present the principles of this endogenous barcoding system, demonstrate its experimental and analytical feasibilities and its power to resolve complex lineages. The work program addresses in a comprehensive manner major open questions on the structure of the hematopoietic system that builds and maintains the immune system. This project ultimately aims at an in depth dissection of unique or common lineage pathways emerging from HSC, and at resolving relationships within cell lineages of the immune system.

Mots-clés : loxp,cre recombinase driven barcoding,hematopoiesis,hematopoietic stem and progenitor cells,high resolution in vivo fate mapping,leukocyte development,maintenance of the blood and immune system
Projet ERC : REGiREG (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : German Cancer Research Center — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : DKFZ
Type d'entité : Recherche
Financement ERC de l'entité : 432623.64 €

The immune system with its complex interactions of cells and molecules needs a very tight and specific interplay of control elements to ensure the establishment and re-establishment of immune homeostasis after challenges. Regulatory T cells (Tregs) are key-players in this regulatory network. It is now well accepted that deficiency or dysfunction of Tregs causes various severe immune disorders due to immune hyperactivation. Conversely, an increased number of Tregs in tumor-bearing individuals suppresses efficient anti-tumor immunity and, thereby, is often associated with poor prognosis. Cancer immunology is now one of the most exciting and promising frontiers in cancer research, and recent clinical trials have proven that immunotherapies driving to activate T cells can induce durable responses. In this sense, harnessing the potential of Tregs is one of the most promising new approaches to control immune function and to treat cancer. This proposal has two objectives: 1, the identification and characterization of tissue-resident Tregs to principally understand the unique features of Treg specialization in tissues and their function in organ-homeostasis, a phenomenon that is hardly understood, but holds great promise for local, tissue-specific immune intervention. 2, to globally target Tregs, including the lymphoid organ Treg pool, by interfering with their survival and or suppression function. We expect from these studies new basic insights into a fascinating and still arcane aspect of organ-homeostasis as maintained by Tregs, as well as novel small molecule inhibitors and candidate molecules that target Tregs at the systemic level, and eventually at a tissue-specific level.

Mots-clés : regulatory t cells,immune regulation,foxp3,tolerance
Projet ERC : USE (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Technion – Israel Institute of Technology — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

The impact of a building design or renovation on the behavior of its intended occupants can be assessed only after the building has been built and occupied (or the renovation has been completed). This is a risky proposition, because design mistakes can cause severe consequences in terms of under-performing buildings, reduced productivity, absenteeism, and general user dissatisfaction. During our ERC-funded project, titled NextGenBim, we were able to develop and demonstrate a method to computationally simulate human behavior in built environments, which allows representing the intended occupants and their activities in a given building. In this PoC we aim to develop a software simulator that allows: (1) to visualize, analyze and evaluate trade-offs between several design options for a new building; and (2) to evaluate the systemic implication of proposed renovations on the operations of a building. The software will potentially impact millions of professionals (architects, civil engineers, internal designers, facility mangers, etc.), especially in the healthcare sector, where large budgets are spent to build and renovate facilities, and in the educational sector, which invests heavily in computer-aided design software to train the next generation of professionals.

Mots-clés : human behavior simulation,built environments,architectural design,building performance,user behavior
Projet ERC : EVOWILD (Horizon 2020, appel 2020, Advanced 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 : 1818417.0 €

The impact of global environmental change on natural populations is both an urgent concern, and an invaluable opportunity to understand how environmental variation shapes evolutionary and ecological processes. This project will combine state-of-the-art genomic and statistical technology with globally distributed studies to build a ground-breaking new understanding of the evolutionary and ecological dynamics of wild populations. At the same time, it will deliver much-needed application of both long-standing and new evolutionary theory. My track record of building the field of wild quantitative genetics together with the new multi-species consortium I have created, means I am uniquely positioned to exert powerful leverage over core questions. My project has three major objectives: (1) to understand variation in fitness and current rates of evolutionary adaptation in the wild, including contributions from social evolution; (2) to determine the effects of environmental variation on natural selection and adaptive evolutionary responses; and (3) to provide comprehensive assessment of the contribution of evolutionary genetic adaptation vs ecological responses to the dynamics of phenotypic traits and population numbers. It will do so using seven exceptional long-term studies of wild mammal populations from across the world: red deer, bighorn sheep, Soay sheep, spotted hyaenas, meerkats, eastern grey kangaroos and Tasmanian devils, all experiencing environmental change such as the effects of climate or disease. The multi-species consortium will enable valuable insight into the generality of the results, which can inform the management of wild populations. The project will also develop new analytical approaches, bringing together the latest quantitative genetic and genomic developments with hierarchical population modelling, which will have application across a broad range of systems.

Mots-clés : evolutionary theory,natural selection,climate change,phenotypic plasticity
Projet ERC : DRIVE (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 1499410.0 €

The impairment of central nervous system (CNS) leads to irreversible loss of vital functions because, unlike young neurons, mature neurons are not able to regenerate. Thus, understanding the detailed mechanisms of axonal growth and repair remains one of the greatest challenges of neurobiology and for society. If the extrinsic factors fail to reach levels required for regeneration, manipulating intrinsic pathways has shown promising results. Particularly, my work demonstrated that the simultaneous activation of mTOR, JAK/STAT and c-myc pathways allows exceptional regeneration with axons close to their targets. However it also exacerbates previously described phenomenon of misguidance with potential aberrant circuit formation. My unique model opens up the possibility to explore these fundamental questions of CNS regeneration. I propose to address the yet unexplored problem of the guidance of regenerating axons in adults in order to promote the formation of a functional new circuit after injury. Indeed what are the modalities of guidance in the adult? Are axons still responsive to developmental guidance cues and are they still expressed? Can regenerative axons form connections with their targets and are these connections functional? To answer these critical questions, I will use the combination of state of the art biochemistry, imaging, and electrophysiology in an in-vivo and ex-vivo model of the visual system to 1) Understand axon guidance in mature system in order to properly drive regenerative axons to their brain targets and avoid aberrant projections, and 2) Analyze the formation of a functional optic nerve circuit after injury. Altogether, these results will generate major breakthroughs in a fundamental but uncovered mechanism of axon guidance during regeneration and the functionality of de novo formed circuits. They will open up new ways for innovative therapeutic development after CNS trauma but also to the large spectrum of neurodegenerative diseases.

Mots-clés : axon regeneration,functional recovery,circuit reformation,axon guidance
Projet ERC : ELDORADO (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Regensburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499953.61 €

The implementation of viable practices for the ecologically cognizant production and consumption of energy and renewable resources rank among the most pressing societal challenges of the 21st century. Against this background, the design and development of innovative concepts for the sustainable use of energy and energy-rich compounds from regenerative sources becomes a matter of profound technological and scientific pertinence. A promising approach that has been put forward in the context of chemical synthesis is the application of visible light as an inexpensive source of energy and air as an abundant and gratuitous oxidant for the derivatization of certain hydrocarbons. Despite the enormous economic and ecological benefits associated with the use of light and air as integral components of redox reactions, the realization of such processes is strikingly limited to very isolated applications. Consequently, this methodological deficit represents a momentous opportunity for modern chemical sciences to lastingly transform the routine lines of action for the oxidative manipulation of organic molecules. A key issue that needs to be taken into consideration for the design of efficient light-driven aerobic oxidation protocols is the identification of proper catalyst systems that allow for the site- and chemoselective activation of individual bonds within polyatomic frameworks. In this regard, the prime objective of the proposed research program is the rational design of non-metallic and in part cooperative catalysis regimes as enabling technologies for the electrophilic activation of non-aromatic carbon–carbon multiple- and carbon-chalcogen single bonds to facilitate a wide and diverse array of heretofore unprecedented oxidative coupling-, addition-, and rearrangement reactions. To demonstrate its utility in a superordinate context, this methodological concept will be applied in highly modular enantioselective syntheses of biologically relevant polyketide natural products.

Mots-clés : organocatalysis,method development,oxidation reactions,alkenes,alkynes,selenium,sulfur,total synthesis
Projet ERC : AUTO.DISTINCT (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Maastricht University — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

The inaccuracy and inconsistency of state-of-the-art tumour volume detection and segmentation has an adverse influence on patient outcomes. Accurately determining the exact location and volume of tumours is a prerequisite for the detection, segmentation, characterisation and therapy response monitoring for any type of cancer. Today, tumour segmentation is performed manually or semi-automatically in a laborious and time-consuming process that exhibits low accuracy and inconsistency. This compromises quality of care by limiting the certainty of lesion detection on medical images, hindering the effectivity of radiotherapy and restricting the accuracy of treatment response monitoring. In this ERC PoC project, we introduce fully automated software for fast, accurate, observer independent and reproducible detection and volumetric segmentation of (lung) tumours and metastases on CT images. Through a unique three-step approach, our software demonstrates superior speed, accuracy and robustness of tumour segmentation over both the state-of-the-art as well as published competing solutions for automated tumour segmentation. Hence, our software has the potential to drastically reduce the adverse impact that inaccurate tumour detection and segmentation currently has on (lung) cancer patient outcomes by: improving the detection of lesions on CT images, increasing the accuracy of radiotherapy treatment to reduce the occurrence of geometric misses, and advance the evaluation of tumour response to treatments through volumetric treatment monitoring. In AUTO.DISTINCT, we will provide technical and commercial proof-of-concept for our novel software. We will solve the remaining technical challenges and develop a user-friendly prototype that can be validated with end users. Moreover, we will develop a business strategy that incorporates all technical, commercial, IPR and regulatory aspects of our invention to ensure successful commercialisation.

Mots-clés : tumour detection,tumour segmentation,lung cancer,nsclc,hypoxia,radiology,radiotherapy,medical oncology,deep learning