Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ViroPedTher (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Navarra — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

The overreaching goal of my lab is to improve the prognosis of patients with high-risk pediatric brain tumors. To this end, I propose to integrate clinical and lab-based research to develop tumor-targeted oncolytic adenoviruses with the capacity to elicit a therapeutic immune response in those tumors. Our research will use novel and relevant models to accomplish the experimental aims. We have previously worked with Delta-24-RGD (DNX-2401) a replication-competent adenovirus that has been translated to the clinical scenario. In 2017, the first clinical trial phase I with DNX-2401 for newly diagnosed Diffuse Intrinsic Pontine Gliomas (DIPG; a lethal pediatric brain tumor) opened propelled by my team. Preliminary results from the first trials revealed that the intratumoral injection of the virus instigated an initial phase of oncolysis followed by a delayed inflammatory response that ultimately resulted in complete regression in a subset of the patients without associated toxicities. I hypothesized that enhancement of the immune component of the DNX-2401-based therapy will result in the complete regression of the vast majority of pediatric brain tumors. In our specific approach, we propose to understand the immune microenvironment of DIPGs and the response to viral therapy in the context of the trial. Moreover, that knowledge will leverage the design of Delta-24-based adenoviruses to recruit lymphocytes to the tumor with the competence of different type of ligands to activate the tumor infiltrating lymphocytes. I expect that this combinatorial innovative treatment will efficiently challenge the profound and inherent tumor immunosuppression and, in turn, will elicit a robust anti-tumor immune response resulting in the significant improvement of the prognosis and quality of life of patients with pediatric brain tumors. This project has the potential to produce a vertical advance in the field of pediatric oncology.

Mots-clés : pediatric brain tumors,oncolytic virus,clinical trial,adenovirus,immune response,biomarkers
Projet ERC : CoSyMoDe (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Konstanz — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1919687.0 €

The past six decades have seen awe-inspiring progress in the science of synthesis. In academia, the assembly of complex molecules (natural products) still poses a challenge, but is no longer a limitation. Yet, application of natural products in industry is still limited. This limitation is reflected by a lack of novel lead structures with a new mode of action — one of the main challenges pharmaceutical industry faces today. With complexity still being a challenge but no longer the limitation, natural products and their unique structures are now ideally suited to fill this gap. However, “target oriented synthesis” (TOS) still dominates the synthetic community, but is not suited for structure diversification. This imposes a poor “return on investment” (ROI) to natural product research in industry. The diminished ROI of TOS is owned to tailor made synthetic routes, strictly applicable to a single molecule with no flexibility, and thus disproportionally increasing time and financial efforts in the search for new lead structures. In this research proposal, the applicant devises an alternative strategic concept termed “Cooperative Synthesis by Molecular Deconvolution” (CoSyMoDe), providing an alternative to TOS, and thus serves as a versatile tool for lead structure discovery. In contrast to TOS, CoSyMoDe targets the most complex congener (alpha) in a set of natural products. All other congeners are obtained by synthetic deconvolution of alpha, rendering the overall process more facile, additionally providing access to a whole set of targets, and thus improving the ROI. To showcase the versatility of CoSyMoDe we have picked one of the most challenging, bioactive, and prominent set of target structures, the taxane diterpenes. Amongst them “cyclotaxanes”, are most complex, and have eluded their total synthesis up to date. We will demonstrate the potential of CoSyMoDe, by solving this synthetic conundrum and thereby push the limits of organic synthesis.

Mots-clés : total synthesis,natural products
Projet ERC : NOVOFLOP (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : TU Wien — Pays : Autriche — Rôle : PI
Acronyme de l'entité : TUW
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 137125.0 €

The physical limits of CMOS scaling and the prohibitively high costs of future technology nodes, allows to foresee the end of further progress of CMOS technology in the near future and emphasizes the dire need to explore alternative technologies and computational principles. Spin as an alternative degree of freedom for computation and information storage attracts much attention due to its nonvolatility, high endurance, fast operation, and CMOS compatibility. Even though first promising results are available, these CMOS/Spintronic hybrid solutions are only competitive in comparison to conventional CMOS technology with respect to power consumption and speed - up to now - they are not able to compete in integration density. Due to the need of continuous conversion between the CMOS and the spintronic signal domain additional transistors are required, which rather leads to an integration density decrease than a densification of the circuit layout. This inspired us to avoid the signal conversion and carry out the complete device operation in the magnetic domain. The resulting non-volatile magnetic flip flop facilitates the spin transfer torque effect and magnetic exchange coupling for computation and thus enables an extremely dense layout. Instead of eight (non-clocked), twelve (clocked) or seven CMOS transistors and two magnetic tunnel junctions (CMOS/Spintronic hybrid) for a RS flip flop a footprint of only 10nmx40nm is sufficient. Furthermore, it can be stacked to a shift register which as well features a very small footprint. The device and its viability has been studied via extensive micromagnetic simulations. For the next step towards market prototypes need to be manufactured and the device performance as well as the corresponding simulation tools need to be further developed. The results of NOVOFLOP will be essential to create a package comprising prototypes, TCAD models, and a manufacturing process for presenting our device to companies and venture capitalists.

Mots-clés : flip flop,latch,spin transfer torque,sequential logic,shift register,non volatile,very large scale integration,vlsi
Projet ERC : UbiArchitect (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : UK Research and Innovation — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UKRI
Type d'entité : Recherche
Financement ERC de l'entité : 1990125.0 €

The posttranslational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. This versatility arises from eight distinct linkage types between individual ubiquitin moieties in polyubiquitin, which co-exist in cells, are independently regulated, and eventually determine the fate of the modified protein. However, ubiquitin chain architecture can be highly complex, and the extent of ‘chain branching’ is unknown. Moreover, ubiquitin also undergoes phosphorylation and acetylation, which can dramatically alter its function. A true appreciation of the complexity in the ubiquitin code can only be achieved when all above aspects are considered, and only then will it be possible to assign cellular readouts to distinct ubiquitination events and differentiate between ubiquitin signals in cells. While the complexity of ubiquitination is daunting, work from many laboratories including my own has exemplified how basic biochemistry, a detailed understanding of mechanism and quantitative mass-spectrometry allows us to study, and eventually understand, the ubiquitin code. In this proposal, new methods and approaches are outlined that will allow a detailed monitoring of polyubiquitin chain architectures from cellular samples (AIM 1), and also lead to an in depth understanding of additional posttranslational modifications, such as ubiquitin phosphorylation and acetylation in cells (AIM 2). Moreover, new research tools for unstudied K6- and K33-linked polyubiquitin will give insights into cellular roles for these linkage types (AIM 3). Our studies will focus on ubiquitination events on mitochondria leading to mitophagy, where unstudied K6-linked chains as well as phospho-ubiquitin are part of complex chain architectures, and mechanisms of signalling are still unclear. Our work will reveal fundamental principles in ubiquitination, and are of high medical relevance due to the links to Parkinson’s disease, infectious disease, and cancer.

Mots-clés : ubiquitin,mitophagy,atypical ubiquitin chains,phospho ubiquitin,e3 ligase,parkin,pink1,rbr e3 ligase,hect e3 ligase,ubiquitin mass spectrometry
Projet ERC : VINCAT (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Vienna — Pays : Autriche — Rôle : PI
Acronyme de l'entité : Univie
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1940025.0 €

The preparation of complex molecular architectures employing multi-component reactions where the number of bond-forming events is maximised is a central goal of the discipline of Organic Synthesis. The contemporary, pressing need for sustainable chemical reactions has raised the demand for novel reaction families that explore the concept of redox-neutrality and proceed with the generation of minimal waste. In this proposal, I present a unified and conceptually novel approach to atom-economical C-C bond formation in challenging contexts without the need for transition metal promoters or reagents. To this end, I propose the innovative harvesting of the potential of vinyl cation intermediates as platforms for the deployment of nucleophilic entities capable of orchestrating rearrangement reactions. The combination of such high-energy intermediates, generated under mild conditions, with the power of carefully designed rearrangements leads to an array of useful new transformations. Furthermore, the very high atom-economy and simplicity of these reactions renders them not only sustainable and environmentally friendly but also highly appealing for large-scale applications. Additional approaches to enantioselective synthesis further enhance the methods proposed. The paradigm proposed herein for the exploitation of vinyl cations will also open up new vistas in the centuries-old aldol reaction and in amination chemistry. This showcases the vast potential of these simple principles of chemical reactivity. The myriad of new reactions and new product families made possible by VINCAT will decisively enrich the toolbox of the synthetic practitioner.

Mots-clés : rearrangements,redox neutral,c c coupling,vinyl cations
Projet ERC : GEOWAKI (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Université Paris-Saclay — Pays : France — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 230000.0 €

The present proposal is concerned with the analysis of geometric non-linear wave equations, such as the Einstein equations, as well as coupled systems of wave and kinetic equations such as the Vlasov-Maxwell and Einstein-Vlasov equations. We intend to pursue three main lines of research, each of them concerning major open problems in the field. I) The dynamics in a neighbourhood of the Anti-de-Sitter space with various boundary conditions. This is a fundamental open problem of mathematical physics which aims at understanding the stability or instability properties of one of the simplest solutions to the Einstein equations. On top of its intrinsic mathematical interest, this question is also at the heart of an intense research activity in the theoretical physics community. II) Non-linear systems of wave and kinetic equations. We have recently found out that the so-called vector field method of Klainerman, a fundamental tool in the study of quasilinear wave equations, in fact possesses a complete analogue in the case of kinetic transport equations. This opens the way to many new directions of research, with applications to several fundamental systems of kinetic theory, such as the Einstein-Vlasov or Vlasov-Maxwell systems, and creates a link between two areas of PDEs which have typically been studied via different methods. One of our objectives is to develop other potential links, such as a general analysis of null forms for relativistic kinetic equations. III) The Einstein equations with data on a compact manifold. The long time dynamics of solutions to the Einstein equations arising from initial data given on a compact manifold is still very poorly understood. In particular, there is still no known stable asymptotic regime for the Einstein equations with data given on a simple manifold such as the torus. We intend to establish the existence of such a stable asymptotic regime.

Mots-clés : non linear wave and kinetic equations,einstein equations,vlasov maxwell and einstein vlasov system,anti de sitter
Projet ERC : CASTELLANY ACCOUNTS (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Bucharest — Pays : Roumanie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 501218.75 €

The present research project focuses on an unjustly neglected corpus of late-medieval sources, the administrative and fiscal accounts (‘computi’) of the castellanies – basic administrative units – of the county of Savoy. I propose a holistic model of analysis that can fully capitalise on the unusual wealth of detail of the Savoyard source material, in order to illuminate some key topics in late-medieval institutional and socio-economic history, from the development of state institutions through administrative and fiscal reform – with particular attention to the transition from personal to institutional accountability – to the question of socio-economic growth, decline, and recovery during the turbulent period of the late-thirteenth to the late-fourteenth century. More broadly, my research into these topics aims to contribute to our understanding of the late-medieval origins of European modernity. The advances of pragmatic literacy, record-keeping, and auditing practices will be analysed with the aid of anthropological and social scientific theories of practice. By comparing the Savoyard ‘computi’ with their sources of inspiration, from the Anglo-Norman pipe rolls to the Catalan fiscal records, the project aims to highlight the creative adaptation of imported administrative models, and thus to contribute to our knowledge of institutional transfers in European history. The project will develop an inclusive frame of analysis in which the ‘computi’ will be read against the evidence from enfeoffment charters, castellany surveys (‘extente’), and the records of direct taxation (‘subsidia’). The serial data will be analysed by building a database; the findings of quantitative analysis will be verified by case studies of the individuals and families (many from the middle social strata) that surface in the fiscal records.
Projet ERC : PAINTBOX (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Lund University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1969445.0 €

The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide and despite great efforts to prevent and cure the disease, the increase persist. There is an urgent need to develop innovative and effective prevention and treatment strategies for T2D. Recent genome-wide association studies were expected to uncover disease-causing mechanisms in common metabolic disorders. Surprisingly, the identified genetic variants only explain a small proportion of the estimated heritability of T2D. Novel studies, going beyond the genome, are therefore needed to identify key mechanisms causing T2D. These studies should focus on pancreatic islets, the tissue of primary pathogenetic importance for diabetes. Also, mechanisms that allow environmental factors to come into play are likely to be important. Epigenetics fulfill such criteria, and our previous work has pioneered epigenetic discoveries in T2D. PAINTBOX is a multidisciplinary research program through which I will combine advanced sequencing technologies and novel epigenetic methods with mathematical models and clinical medicine to develop new prediction and treatment strategies for T2D. Innovative techniques and access to some of the world´s best patient cohorts permit me to address the role of epigenetics in development of T2D in new ways. The annotation of these discoveries will be done using genome-wide epigenomic and targeted gene-editing tools together with mathematics, whereas the translation of those findings will be achieved using powerful prospective cohorts for T2D and clinical studies. PAINTBOX capitalizes on the largest existing human islet cohort and large prospective cohorts, and expertise that I have built-up over the past twenty years, but also exploits novel epi-genomic and gene-editing technologies that have not previously been used for T2D. I expect this novel interdisciplinary project to generate groundbreaking results that opens up new horizons for prediction, prevention and treatment of T2D.

Mots-clés : endocrinology,type 2 diabetes,pancreatic islets,insulin secretion,dna methylation,histone modifications,non coding rna,biomarkers,prediction,epigenetic editing,treatment,hdac inhibitors
Projet ERC : DEEPEN (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1983886.0 €

The principles of sensory perception are still a large experimental and theoretical puzzle. A strong difficulty is that perception emerges from networks of recurrently connected brain areas whose activity and function are poorly approximated by current generic mathematical models. These models also fail to explain many of the fundamental structures effortlessly identified by the brain (shapes, objects, auditory or tactile categories). I here propose to establish a new approach combining high-throughput population recoding methods with a tailored theoretical framework to derive computational principles operating throughout sensory systems and leading to biologically structured perception. This approach follows on the recent mathematical proposal, suggested by Deep Machine Learning methods, that complex perceptual objects emerge through series of simple nonlinear operations combining increasingly complex sensory features along the sensory pathways. Starting with the mouse auditory system as a model pathway, we will recursively extract, with model-free methods, the main nonlinear sensory features encoded in genetically tagged output and local neurons at different processing stages, using optical and electrophysiological high density recording techniques in awake animals. The role of these features in perception will be identified with behavioural assays. Specific intra- and interareal feedback connections, typically not included in Deep Leaning models, will be opto- and chemogenetically perturbed to assess their contribution to precise nonlinearities of the system and their role in the emergence of complex perceptual structures. Based on these structural, functional and perturbation data, a new generation of well-constrained and predictive sensory processing models will be built, serving as a platform to extract general computational principles missing to link neural activity to perception and to fuel artificial neural networks technologies.

Mots-clés : two photon calcium imaging,auditory system,deep learning
Projet ERC : IDEM (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
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 : 1433399.99 €

The problem of biological identity (what counts as one individual organism, and what makes each individual organism “the same” though it constantly changes through time?) has a long history both in philosophy and in science. Recent data coming from immunology, microbiology and developmental biology may revolutionize our conception of the construction of biological identity through time, by showing that this construction depends crucially on environmental factors and, most importantly, on a constant dialogue with symbiotic microorganisms integrated into the organism. IDEM, a fundamentally interdisciplinary project at the interface between philosophy and biology, aims at: i) determining to what extent it is adequate to see this shift as an ongoing “microbial revolution” in today’s biology; ii) understanding the exact processes by which developmental processes in organisms depend on microbial symbionts; iii) asking whether the role of the immune system (usually seen as a system that rejects genetically foreign elements from the body) in the maintenance of the organism needs to be reevaluated; iv) how traditional conceptions of biological individuality will be modified by this revolution. If funded, this project will provide a new understanding of the way living things are continuously constructed through time and interact with their biotic environment.

Mots-clés : philosophy of biology,symbiosis,microbiota,immunity,development,identity,self