Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : DHARMA (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Humboldt-Universität zu Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2432423.75 €

Censuses report over a billion “Hindus” in the world today. But what is “Hinduism”? In answer, many accounts describe the doctrinal evolutions of various quite different currents of thought. To try to reply using material and social evidence is difficult because so many vital primary sources for institutional history remain inaccessible. What were the material foundations of the constellation of religious movements today classed as “Hindu”? How have different forms of religious agency shaped the institutional and religious landscape of a large sweep of Asia? How did such “Hindu” traditions, associated primarily with the ideas and practices of ascetics questing for liberation, become institutionally rooted? And what were the repercussions of the widespread patronage of pious foundations? Three types of sources will be examined: inscriptions, manuscripts, archaeological remains. Inscriptions are crucial because most of our historical knowledge of early South and Southeast Asia is based on epigraphy. We will explore, mine and diffuse these sources with the tools of digital humanities (rich mark-up of proper-names, technical terms, geodata, etc.). In order to contextualise epigraphy, unpublished prescriptive texts and new archaeological data will be adduced. Our goal is to identify and to map regional and interregional patterns of patronage. The actors are varied: “lettrés”, holy men and priestly intermediaries, as well as their patrons, often grandees of the state; but also cenobitic communities with their statutes, their libraries, their educational activities, and their incipient bureaucracy. Through a comparative approach (concentrating on “Hinduism”, but also considering the so-called “heretic” religions Buddhism and Jainism), and in a broad range of regional contexts, we shall attempt to uncover with unprecedented historical depth the complex interplay of religion, state and society in a formative period, the “Śaiva Age”, between the 6th and 13th centuries.

Mots-clés : south asia,southeast asia,religion,sanskrit,tamil,kannada,telugu,old javanese,khmer,indology,epigraphy,archaeology,state,society,patronage,indianisation,digital humanities
Projet ERC : DHARMA (Horizon 2020, appel 2018, Synergy grants)
Entité participante : École française d'Extrême-Orient — Pays : France — Rôle : PI
Acronyme de l'entité : EFEO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 4405891.0 €

Censuses report over a billion “Hindus” in the world today. But what is “Hinduism”? In answer, many accounts describe the doctrinal evolutions of various quite different currents of thought. To try to reply using material and social evidence is difficult because so many vital primary sources for institutional history remain inaccessible. What were the material foundations of the constellation of religious movements today classed as “Hindu”? How have different forms of religious agency shaped the institutional and religious landscape of a large sweep of Asia? How did such “Hindu” traditions, associated primarily with the ideas and practices of ascetics questing for liberation, become institutionally rooted? And what were the repercussions of the widespread patronage of pious foundations? Three types of sources will be examined: inscriptions, manuscripts, archaeological remains. Inscriptions are crucial because most of our historical knowledge of early South and Southeast Asia is based on epigraphy. We will explore, mine and diffuse these sources with the tools of digital humanities (rich mark-up of proper-names, technical terms, geodata, etc.). In order to contextualise epigraphy, unpublished prescriptive texts and new archaeological data will be adduced. Our goal is to identify and to map regional and interregional patterns of patronage. The actors are varied: “lettrés”, holy men and priestly intermediaries, as well as their patrons, often grandees of the state; but also cenobitic communities with their statutes, their libraries, their educational activities, and their incipient bureaucracy. Through a comparative approach (concentrating on “Hinduism”, but also considering the so-called “heretic” religions Buddhism and Jainism), and in a broad range of regional contexts, we shall attempt to uncover with unprecedented historical depth the complex interplay of religion, state and society in a formative period, the “Śaiva Age”, between the 6th and 13th centuries.

Mots-clés : south asia,southeast asia,religion,sanskrit,tamil,kannada,telugu,old javanese,khmer,indology,epigraphy,archaeology,state,society,patronage,indianisation,digital humanities
Projet ERC : SLaMM (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Italian Institute of Technology — Pays : Italie — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1412234.64 €

Central nervous system (CNS) tumors are an important cause of morbidity and mortality worldwide. Among them, glioblastoma multiforme (GBM) is the most aggressive and lethal, characterized by extensive infiltration into the brain parenchyma. Under the standard treatment protocols, GBM patients can expect a median survival of 14.6 months, while less than 5% of patients live longer than 5 years. This poor prognosis is due to several factors, including the highly aggressive and infiltrative nature of GBM, resulting in incomplete resection, and the limited delivery of therapeutics across the blood-brain-barrier (BBB). The present project aims at addressing these therapeutic challenges by proposing a nanotechnology-based approach for the treatment of GBM, focused on the selective uptake of drug-loaded multifunctional magnetic solid lipid nanoparticles (SLNs). An external magnetic guidance will help the SLN accumulation on the cerebral endothelium, where, owing to their lipid nature, they will be allowed to enter the CNS. Here, appropriate surface ligands will drive their internalization inside cancer cells. The chemotherapeutic payload will undergo release, allowing a targeted pharmaceutical treatment that will be combined to hyperthermia upon appropriate radiofrequency application. A synergic attack against GBM will thus be performed, consisting of a chemical attack thanks to the drug, and a physical attack thanks to hyperthermia, that will dramatically enhance the possibilities of therapeutic success. By demonstrating the effectiveness of the platform to cross the BBB and to support tumor regression, a huge impact on human healthcare is envisioned. Moreover, further outcomes of this project are expected by considering the development of nanotechnology-based, multi-functional solutions that can easily be adapted to many other high-impact diseases, in particular at the brain level, where BBB crossing poses a crucial obstacle to many therapeutic approaches.

Mots-clés : smart nanomaterials,drug delivery,drug targeting
Projet ERC : DNACom (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Eindhoven University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU/e
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149770.0 €

Changes in human microRNA (miRNA) levels are associated with several important human diseases. Monitoring changes in miRNA levels would enable clinicians to perform diagnosis and evaluate therapeutic efficacy of drugs. In principle, changes in a miRNA signature could be detected by existing methods such as quantitative reverse transcription PCR (RT-qPCR). However, the experimental complexity and computational analysis of the data prevents the measurements of miRNA signatures in a clinical setting. DNA-based molecular computers combine multiplex detection of DNA and RNA strands with molecular computation and are thus able to process and classify miRNA signatures into easy interpretable answers. In my ERC starting grant BioCircuit, we have made a technological breakthrough by compartmentalizing DNA-based molecular computers inside semipermeable micrometer-sized compartments made from a Bovine serum albumin (BSA) polymer conjugate. We have shown that compartmentalization of DNA circuits improves their speed by an order of magnitude and decreases their overall leakiness. Importantly, our work has revealed that this platform is capable of distributed sensing and processing of DNA and RNA strands. In 'DNACom' we will 1) establish the technical proof of concept of compartmentalized DNA computers for in-vitro molecular diagnostics (IVDs) and 2) validate the commercial application of compartmentalized DNA circuits as low-cost, portable point-of-care devices for detection and classification of microRNA signatures.

Mots-clés : dna computing,in vitro diagnostics
Projet ERC : GameofGates (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Austrian Academy of Sciences — Pays : Autriche — Rôle : PI
Acronyme de l'entité : OAW
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2389782.0 €

Chemical exchange between cells and their environment occurs at cellular membranes, the interface where biology meets chemistry. Studying mechanisms of drug resistance, I realized that SoLute Carrier proteins (SLCs), not only represent the major class of small molecule transporters, but that they are encoded by one of the most neglected group of human genes. I identified a case where an SLC controls the activity of mTOR, suggesting that other SLCs may be involved in signalling. This formed the basis for the GameofGates project proposal. The name refers to SLCs as a metaphor for cellular gates coordinating access to resources following game rules that are largely unknown but worth learning, as the acquired knowledge could impact our understanding of cellular physiology and open avenues for innovative treatment of human diseases. GameofGates (GoG) plans the investigation of SLC function by comprehensively and deeply charting the genetic and protein interaction landscape of SLCs in a human cell line, while monitoring fitness, drug sensitivity and metabolic state. GoG aims at functionally de-orphanize many SLCs by assessing hundreds of thousands of genetic interactions as well as thousands protein and drug interactions. I hypothesize that SLC action is linked to signalling pathways and plays an important role in integration of metabolism and cell regulation for successful homeostasis. I propose that whole circuits of SLCs may be linked to particular nutrient auxotrophy states and that knowledge of these dependencies could instruct assessment of vulnerabilities in cancer cells. In turn, these could be pharmacologically exploited using existing or future drugs. Overall, GoG should position enough pieces into functional and regulatory networks in the SLC puzzle game to facilitate future work and motivate the community to embrace investigation of SLCs as conveyers of metabolic and chemical integration of cell biology with physiology and, in a wider scope, ecology.

Mots-clés : solute carriers,metabolomics,membrane transport,systems biology,drug sensitivity
Projet ERC : HiChemSynPro (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Université de Strasbourg — Pays : France — Rôle : Partner
Acronyme de l'entité : UNISTRA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 970075.0 €

Chemical protein synthesis is an indispensable method in chemical and synthetic biology. However, at the present moment, it is laborious and involves multiple optimization and purification steps. High-throughput approaches for total synthesis of combinatorial libraries of custom-modified protein variants are needed. To change the situation, the work will be carried out in two directions: (1) implementation of microfluidic techniques for automation, miniaturization and multiplexing of experimental steps involved in the total synthesis of proteins, and (2) design and synthesis of novel catalytic proteins for efficient enzyme-assisted peptide ligations under denatured conditions. This innovative research technology will allow robust chemical synthesis of protein libraries with (100–10,000)-compounds with natural and unnatural modifications, bearing variety of post-translational modifications and also protein-like biopolymers. In this project, the new methodology will be validated by chemical synthesis of library of phosphorylated analogues of high mobility group protein A (HMGA), which is involved in gene-transcription and cancer development. Other potential future applications include protein design, biological problems where post-translational modifications play a crucial role (ranging from the ‘histone code’ hypothesis to understanding long-term memory) and functional annotation of newly discovered genes.

Mots-clés : chemical protein synthesis,microfluidics,enzyme engineering,post translational modifications,combinatorial protein libraries
Projet ERC : DINAMIX (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
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 : 1499307.0 €

Chemical samples often come as solution mixtures. While advanced analytical methods exist for samples at equilibrium, the information on components and their interactions that may be accessed for the frequent and important case of out-of-equilibrium mixtures is much more limited. The DINAMIX project will tackle this challenge and provide detailed, molecular-level information on out-of-equilibrium mixtures. The proposed concept relies on diffusion nuclear magnetic resonance (NMR) spectroscopy, a powerful method that separates the spectra of mixtures’ components and identifies interactions, in correlation with structural insight provided by NMR observables. While classic experiments require several minutes, spatial encoding (SPEN) in principle makes it possible to acquire data orders of magnitude faster, in less than a second. The PI has recently demonstrated that SPEN diffusion NMR is a general concept, with the potential to provide real-time information on out-of-equilibrium mixtures. These include a vast range of systems undergoing chemical change, as well as the important class of “hyperpolarised” solution mixtures generated by dissolution dynamic nuclear polarisation (D-DNP). D-DNP indeed provides dramatic NMR sensitivity enhancements of up to 4 orders of magnitude, which however last only for a short time in solution. In the DINAMIX project, we will develop i/ novel robust and accurate real-time diffusion NMR methods, ii/ advanced algorithms for data processing and analysis, iii/ protocols for sensitive component identification. We will exploit the resulting methodology for mechanistic investigations into catalytic organic and enzymatic reactions. The real-time diffusion NMR analysis of systems that are out-of-chemical equilibrium, far-from-spin-equilibrium or both will provide transformative insight on mixtures, with applications in chemical synthesis, supramolecular and polymer science, structural biology, and microstructural studies in materials and in vivo.

Mots-clés : nmr spectroscopy,hyperpolarisation
Projet ERC : FRICatANIONS (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Münster — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WWU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1847281.66 €

Chemical transformations comprise the polarization of the reacting species. As a consequence, partially or fully charged reagents and intermediates are omnipresent in chemistry. Although anion-binding processes are well-known for their crucial role in molecular recognition, this type of phenomenon has only recently been utilized for catalysis. Since catalytic reactions are of utmost relevance to construct valuable chemicals and materials, this mode of catalytic chemical activation might be the key for the future design of original and more efficient synthetic transformations. However, the effects of anions in catalytic processes are still largely unknown. Aiming at providing a novel general synthetic toolbox, in this project I propose several anion-binding activation concepts to solve current challenging catalytic synthetic problems. To achieve this goal, structurally different chiral anion-binding catalysts will be developed and incorporated into the existing limited palette of catalyst library. Furthermore, I propose a significant expansion of the application scope of anion-binding catalysis based on the activation and modulation of anionic nucleophiles and oxidants to develop organocatalytic reactions such as halogenations and oxidations, including the asymmetric functionalization of C-H bonds. In addition, anion-binding processes will be used to facilitate key steps in cross-coupling reactions such as the transmetallation, as well as the photoactivity modulation of readily available photosensitizers and the introduction of asymmetric photocatalysis involving radical-anions. The proposed groundbreaking approaches will revolutionize not only anion-binding catalysis but also all the scientific areas relying on catalytic synthetic methods. Thus, the results derived from this project will have a tremendous impact in diverse fields such as catalysis, organic synthesis and material sciences, as well as in economical, environmental and industrial issues.

Mots-clés : catalysis,asymmetric reactions
Projet ERC : INSIGHT (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : University of Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Chemicals detection is a crucial problems that Chemistry is addressing since its origin and one of the most important in the everyday life (diagnosis, environment analysis). The most common analytical techniques (chromatography, mass spectrometry, Elisa assays) are able to efficiently separate and detect the target compound but provide only indirect information on its identity and may fail in the identification of new compounds. On the other hand, Nuclear Magnetic Resonance (NMR) spectrometry is probably the most powerful technique in identifying organic compounds. Unfortunately, even if highly desired, a robust method that may allow the use of NMR for analysing mixtures of compounds does not exist. The research activity carried out by Fabrizio Mancin as PI of the ERC project MOSAIC has recently led to the invention of “NMR sensing”, a new method that allow both the detection and identification of organic molecules, based on the use of NMR spectrometry and nanoparticles. In a simplified picture, the nanoparticles added to the sample are able to “capture” and “label” the target molecule in such a way that the NMR experiment sees only the target and is not disturbed by the other compounds present in the sample. In this way, detection, unambiguous identification and quantification of the analyte are simultaneously possible in a single experiment. This method, already covered by a Patent, showed excellent preliminary results and could find several application in the chemical analysis and diagnostic fields. The goal of this Proof of Concept application is to bring the “NMR sensing” method at the level of an attractive commercial proposal. In particular, the plan include technical testing and preliminary product realization, recruitment of financial and management competencies, collection of information and data capable to indicate the best strategy to create of a start-up company to be presented to venture capitalists/industrial partners to raise further funding.

Mots-clés : nanoparticles,detection,analysis,spin off
Projet ERC : safenolaTiCancerDrug (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Hebrew University of Jerusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Chemotherapy is the most common line of treatment for various cancer types, but it generally suffers from severe side effects. Cisplatin is a highly effective metallodrug employed in the clinic, limited by severe and irreversible nephro- and neurotoxicities and resistance development. Therefore, developing highly and widely effective chemotherapy that is non- or substantially less- toxic should impact immediately and significantly the welfare of society. The titanium metal is an attractive Pt alternative, as it is bio-friendly and non-toxic. Titanium dioxide, the final decomposition product of Ti complexes in water, is a safe material often found in food and cosmetics. Nevertheless, the rapid dissociation of past Ti complexes in water has hampered their development into drugs. Under an ERC-StG grant followed by an ERC-CoG grant, the PI has developed Ti(IV) complexes that are stable for weeks in water, with high in vitro activity toward numerous cells (also established on the NCI-60 panel of the NIH) and in vivo toward murine and human models with no clinical sights of toxicity in treated mice at effective doses, where mortality occurred in control animals treated with cisplatin at similar doses. Pharmaceutical entities have shown specific interest in taking the proposed compound 1 into clinical trials phase I. Some experiments are still required before an agreement can be made, as proposed herein. Through the parent ERC-CoG, mechanistic analyses are ongoing, but no animal studies are permitted. Thus, through the proposed study: (a) pharmacokinetic studies on compound 1 by ICP-MS will determine absorption, bio-distribution, and excretion; (b) In vivo studies of different models and with varying concentrations and formulation types will determine the therapeutic potential; (c) iv vivo combination studies will identify possible lines of treatments. These studies should promote the interaction with pharmaceutical companies to enable compound 1 to enter clinical trials.

Mots-clés : anticancer metallodrugs,metal based chemotherapy,cisplatin