Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : GENE FOR CURE (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
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 : 2137827.52 €

Given that (i) not all patients with a monogenic disease affecting the lymphohaematopoietic system have an HLA-genoidentical sibling donor and (ii) severe immunological complications worsen the outcome in HLA-partially-matched hematopoietic stem cell transplantation (HSCT), the genetic modification of autologous hematopoietic stem cells (HSCs) has become a powerful curative treatment option for these individuals. The present project seeks to further consolidate the rationale for replacing HLA-partially-matched HSCT with a gene therapy approach. Wiskott-Aldrich syndrome is a primary immunodeficiency whose severity is due to impairment of both lymphoid and myeloid cell function. We have reported robust evidence showing that the infusion of gene-corrected autologous HSCs enables the restoration of the T cell function. However, we are still cautious with regard to claiming the stable correction of autoimmunity and thrombocytopenia. Accordingly, we plan to thoroughly monitor long-term B cell functional outcomes and the platelet count in our treated patients. Moreover, we wish to extend the gene therapy approach to the SCID caused by mutations in the DLREIC gene, since the long-term post-HSCT outcomes are particularly poor. The preclinical work has been completed; initiation of a clinical protocol is the next step. Immune-dysregulation polyendocrinopathy enteropathy X-linked (IPEX) and sickle cell anaemia (SCA) are the last two target diseases. IPEX is a devastating disease caused by mutation of FOXP3 transcription factor; it may be possible to correct it by infusing gene-modified CD4+Tcells. We intend to accumulate the data required to prove our working hypothesis. SCA is a worldwide public health issue. We are seeking to improve the conventional gene therapy procedure and to evaluate the efficacy of CrisP/Cas9-mediated disruption of the CIS-regulatory elements required for HbF silencing. This disruption may provide a cure for SCA.

Mots-clés : genetic diseases of the hematopoietic stem cells,blood cells
Projet ERC : CoherentGlasses (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
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 : 1486931.0 €

Glasses are mysterious materials. Fundamental blocks in many natural and technological processes, still, their properties keep puzzling a large community of scientists nowadays. Following different experimental routes, materials as diverse as colloidal suspensions, emulsions and viscous liquids can be driven in an out-of-equilibrium state, where they solidify under conditions that still remain unknown. This process, traditionally called glass transition, leads to many intriguing phenomena as the emergence of multiple relaxations processes, dynamical heterogeneities, crossovers between distinct amorphous states, and uncommon mechanisms of particle motions. Within the large family of disordered systems, structural glasses play a key role being often considered as archetypes of out-of-equilibrium materials. Despite decades of studies, a microscopic theory of glasses is still missing due to the difficulty to probe their atomic motion with experiments and simulations. Few years ago, I used coherent x-rays to perform the first worldwide experiments probing the atomic motion of glasses. My works reported on a surprising glassy dynamic reminiscent of an anomalous stress-driven particle motion observed in some soft systems. Due to severe technical constraints, the studies performed so far were limited to the external, tiny portion of the huge "iceberg” of dynamical features occurring at the atomic level, whose comprehension would enable substantial advances in the frontiers of knowledge. Thanks to the new possibilities offered by coherent x-rays, now is the right time to unveil the atomic dance of glasses in all its complexity with the CoherentGlasses project. Following four challenging experimental Research Objectives, we will provide a coherent picture of the microscopic dynamic and structural features accounting for the above discussed fascinating phenomena in glass-formers. A successful project keeps the promise to boost our knowledge on out-of-equilibrium material.

Mots-clés : x ray photon correlation spectroscopy
Projet ERC : GlioDx (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Vrije Universiteit Amsterdam — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : VU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

Glioblastoma (GBM) is a devastating primary brain cancer which affects about 230.000 people annually. The choice for treatment depends on the subtype of GBM. An accurate detection of tumour subtype is therefore essential for a personalised targeted treatment. Diagnosis, classification and treatment monitoring occurs currently by radiology and repeated invasive biopsies. There is a need for non-invasive, actionable biomarkers for early-stage diagnosis and disease monitoring. During our ERC research, we discovered that mRNA sequenced from tumour-educated platelets enables for pan-cancer, multiclass cancer and companion diagnostics. We were able to distinguish between primary and metastasised tumours in the brain and also establish the molecular subtype of the tumour. These findings provide strong support for using tumour-educated platelets as a biomarker for early stratification, diagnosis and prognosis for personalised GBM treatment. As a proof-of-concept of our innovative diagnostic tests, we will validate the proprietary algorithms underlying these tests specifically in GBM patients. To achieve this, we focus on the differentiation of glioblastoma subtype based on the platelet mRNA profile. In addition we will validate treatment monitoring and response prediction to an EGFR targeted drug in GBM patients. GlioDx will also assess the feasibility to commercialise the technology. The team has developed several business and IP models which need to be assessed thoroughly through in-depth market research and business planning activities. The results need to be consolidated into a strong business plan that will be presented to investors and strategic investors.

Mots-clés : glioblastoma,cancer,blood platelets,egfr,treatment,diagnostic
Projet ERC : GlioDx (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Glioblastoma (GBM) is a devastating primary brain cancer which affects about 230.000 people annually. The choice for treatment depends on the subtype of GBM. An accurate detection of tumour subtype is therefore essential for a personalised targeted treatment. Diagnosis, classification and treatment monitoring occurs currently by radiology and repeated invasive biopsies. There is a need for non-invasive, actionable biomarkers for early-stage diagnosis and disease monitoring. During our ERC research, we discovered that mRNA sequenced from tumour-educated platelets enables for pan-cancer, multiclass cancer and companion diagnostics. We were able to distinguish between primary and metastasised tumours in the brain and also establish the molecular subtype of the tumour. These findings provide strong support for using tumour-educated platelets as a biomarker for early stratification, diagnosis and prognosis for personalised GBM treatment. As a proof-of-concept of our innovative diagnostic tests, we will validate the proprietary algorithms underlying these tests specifically in GBM patients. To achieve this, we focus on the differentiation of glioblastoma subtype based on the platelet mRNA profile. In addition we will validate treatment monitoring and response prediction to an EGFR targeted drug in GBM patients. GlioDx will also assess the feasibility to commercialise the technology. The team has developed several business and IP models which need to be assessed thoroughly through in-depth market research and business planning activities. The results need to be consolidated into a strong business plan that will be presented to investors and strategic investors.

Mots-clés : glioblastoma,cancer,blood platelets,egfr,treatment,diagnostic
Projet ERC : GlioVac (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Karolinska Institutet — Pays : Suède — Rôle : PI
Acronyme de l'entité : KI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149693.0 €

Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with marginal life expectancy even with the most aggressive available therapy. We have identified a previously unanticipated vulnerability of GSCs which when targeted, leads to a rapid and complete cell death of all tumor cells isolated from nine different patients diagnosed with GBM. The cellular mechanism has been identified and involves an increased vulnerability of GSCs to massive vacuolization which can be induced by a small molecule, termed Vacquinol-1. The vacuolization results from an induction of massive macropinocytosis leading to cytoplasmic membrane rupture and cell death. Vacquinol-1 reduces viability in vitro with approximately 70 times greater potency than current chemotherapy and efficiently and significantly reverses disease and prolongs survival in animal models of human GBM. Vacquinol-1 is highly selective for glioblastoma cells and is not present in other examined cell types, including astrocytes from the brain. Vacquinol-1 has favorable pharmacokinetics, oral bioavailability and exhibits excellent overall preclinical characteristics. Synthetic chemical expansion of Vacquinol-1 reveals an exquisitely delicate structure activity relationship. IP protection has been filed. In order to be able to validate this discovery into an innovation and possible commercialization we need to: 1) Compare potency and efficacy with competing compounds in development stage. 2) Establish optimized dosage regimen from in vitro and in vivo cytotoxicity and brain exposure measurements. 3) Develop a GMP-compatible stereo-selective synthesis of an appropriate Vacquinol-1 isomer for amending composition of matter to patent and pre-GLP/GLP toxicological and phase I clinical trials. 4) Together with Karolinska Institutet Innovations AB protect the intellectual property, validate commercialization potential and establish a development plan.

Mots-clés : glioma,glioblastoma,macropinocytosis,vacuolization,cancer,small molecule
Projet ERC : PRINCIPLES (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of Nottingham — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2496465.0 €

Global warming and Covid19 are two prime examples of problems that require cooperation at a very large scale. A failure to cooperate, that is, to act in one’s self-interest rather than the collective interest, could spell a bleak future for humanity. When are people prepared to play their part in the solution of these fundamental problems? Current behavioural models of cooperation from across the social sciences, including economics, are inadequate for answering this fundamental question, because they typically focus on one narrow aspect of people’s behaviour, but people might be motivated by different factors at the same time. Hence, to make progress, an integrated approach is needed. The major ambition of my interdisciplinary research programme is to achieve synergy by combining insights and methods from economics, sociology, and moral and social psychology into a novel experimentally tested framework thereby making a major step forward in the creation of a unified science of human cooperation. Rule following is the most basic behaviour to achieve large-scale cooperation. I will use it as a first step to develop, and experimentally test a comprehensive model of behavioural principles of cooperation. Second, I will then employ the framework to systematically investigate behavioural links between previously disjointed behavioural principles as developed across the social sciences. I also use the model to provide comprehensive new behavioural analyses of the most important models of social dilemmas. Finally, I will use the new framework in representative samples from major economies around the globe to explain people’s behaviour in relevant large-scale cooperation problems, most importantly caring for the climate, by using incentivised experiments. PRINCIPLES will equip researchers and policy makers across disciplines with behavioural principles, tools and data to study problems of cooperation using an interdisciplinary and experimentally tested framework.

Mots-clés : behavioural economics,large scale cooperation,rule following,incentives,perceptions,experiments,representative samples
Projet ERC : CITIZINGLOBAL (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : CERCA Institution — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CERCA;I-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 960000.0 €

Globalization has brought the world economy unprecedented prosperity, but it poses governance challenges. It needs governments to provide the infrastructure for global economic integration and to refrain from destructive protectionism; yet it can engender popular discontent and a crisis of democracy. My proposal will study when trade- and productivity-enhancing policies enjoy democratic support; why voters may support instead inefficient surplus-reducing policies; and how political structure reacts to globalization. Part A studies the puzzling popularity of protectionism and how lobbies can raise it by manipulating information. It will study empirically if greater transparency causes lower trade barriers. It will introduce salience theory to political economics and argue that voters overweight concentrated losses and disregard diffuse benefits. It will show that lobbies can raise protection by channeling information to insiders and advertising the plight of displaced workers. Part B studies inefficient infrastructure policy and the ensuing spatial misallocation of economic activity. It will show that voters’ unequal knowledge lets local residents capture national policy. They disregard nationwide positive externalities, so investment in major cities is insufficient, but also nationwide taxes, so spending in low-density areas is excessive. It will argue that the fundamental attribution error causes voter opposition to growth-enhancing policies and efficient incentive schemes like congestion pricing. Part C studies how the size of countries and international unions adapts to expanding trade opportunities. It will focus on three forces: cultural diversity, economies of scale and scope in government, and trade-reducing border effects. It will show they explain increasing country size in the 19th century; the rise and fall of colonial empires; and the recent emergence of regional and global economic unions, accompanied by a peaceful increase in the number of countries.

Mots-clés : political economics,elections,voter information,political structure,special interest politics,trade policy,infrastructure policy,cities,country size,international unions,globalization
Projet ERC : REFUGEDEV (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498392.5 €

Globally, nearly one in every 100 humans is now either a refugee or internally displaced. Over 95% of the refugee population is concentrated in the developing world, 60% of which are in fragile states. The 36 most fragile countries in the world account for 2.6% of global GDP but host 71% of the world’s population of forcibly displaced people. This stands in contrast to the 4% of world refugees currently hosted by the US or the 5% of refugees seeking asylum in Europe. The number of refugees in the developing world is only expected to increase with worsening conflict in several countries, particularly in Sub-Saharan Africa. This trend poses dramatic and immediate economic challenges to low-income, fragile states in the developing world, while increasing the threat of economic and political instability in the developed world due to growing immigration and demand for asylum. Recent events have showcased that managing refugee flows may be a defining challenge of our time. At the heart of this challenge is the (lack of) economic integration of refugees into the country of first asylum in the short-run, and into their country of origin in the long-run. The main objectives of REFUGEDEV are to: 1) quantify labor market effects of refugees on host communities in the developing world; 2) examine how these effects respond to exogenous changes in the distribution of skill, income and assets of refugees and host communities; 3) measure the impact of refugee integration on attracting subsequent waves of refugees and economic migrants; 4) identify the long-term impact of forced displacement on the socioeconomic outcomes of repatriated refugees once conflict subsides. REFUGEDEV will generate new datasets from archival, administrative and primary survey data on the economic trajectories of refugees and of host communities; and it will combine experimental and quasi-experimental empirical strategies to identify causal relationships between forced displacement, poverty and growth.
Projet ERC : Multi-Pop (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : Liverpool John Moores University — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : LJMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1429439.0 €

Globular clusters (GCs) are among the oldest luminous sources in the universe, bearing witness to the earliest stages of galaxy formation as well as their evolution to the present day. While GCs have played a pivotal role in our understanding of the assembly of galaxies, their full potential remains unfulfilled due to our lack of understanding of how they form. One of the largest stumbling blocks has been the anomalous chemistry (both metallicity distributions and abundance patterns) of GCs relative to field stars within galaxy. Here, we will turn the problem around and exploit these differences to understand the co-evolution of GCs and their host galaxies. Our understanding of GCs and their formation has undergone a radical change in the past two decades. First, it is now clear that while traditionally thought of as the quintessential simple stellar populations (i.e., all stars within a cluster have the same chemical abundances and age), globular clusters host multiple stellar populations with spreads in He, many light elements (e.g., Na, O, Al) and even Fe in a few cases. Secondly, GCs, once thought to only be able to form in the special conditions present in the early Universe, are now known to be still forming today (known as Young Massive Clusters - YMCS). These two facts have opened up a new window into the interconnectedness of GC and galaxy formation and co-evolution. In this project we will quantitatively test current GC formation models with observations of YMCs, as well as organise what is known of the stellar populations within GCs (e.g., abundance spreads, CMD morphologies), providing, for the first time, a global view (i.e., which characteristics are specific to individual GCs and which are common to all GCs). These results, when combined with what is known about massive cluster formation in the local universe, will provide an unprecedented opportunity to use GCs to constrain the hierarchical assembly of galaxies.
Projet ERC : GlycoEdit (Horizon 2020, appel 2017, Starting 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 : 1500000.0 €

Glycosylation, the expression of carbohydrate structures on proteins and lipids, is found in all the domains of life. The collection of all glycans found on a cell is called the “glycome” which is information rich and a key player in a plethora of physiological and pathological processes. The information that the glycome holds can be written, read and erased by glycosyltransferases, lectins and glycosidases, respectively. The immense structural complexity and the fact that glycan biosynthesis is not under direct genetic control makes it very difficult to study the glycome. The glycosylation pattern of cancer cells is very different from that of healthy cells. It is still unclear whether aberrant glycosylation of cancer cells is a cause or consequence of tumorigenesis but it is associated with aggressive and invasive forms of cancer and hence poor prognosis. Malignant glycans are directly involved in a number of mechanisms that suppress the immune response, increase migration and extravasation (metastasis), block apoptosis and increase resistance to chemotherapy. The aim of this proposal is develop new glycomimetics that can be used to edit the glycome of cancer cells to target such evasive mechanisms. Using combinations of new glycan based inhibitors, a coordinated attack on the cancer glycome can be carried out which is expected to severely cripple the cancers ability to grow and metastasize. This will make the tumor more susceptible to immune mediated killing which may be further enhanced in combination with other anti-cancer strategies. To minimize systemic side effects, new methods for the local delivery/activation of glycan inhibitors will be developed. The developed methods are expected to have a much broader than just cancer alone since the studied mechanisms are also associated with autoimmune and neurodegenerative disease.

Mots-clés : glycosylation,carbohydrates,chemical biology