Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PyraSig (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 169092.09 €

Quorum sensing (QS) is a bacterial cell–cell communication process involving the production, release, and detection of extracellular signal molecules called autoinducers. QS is key to all microbiology as it enables otherwise solitary bacteria to coordinate complex cooperative tasks such as biofilm formation and pathogenesis. Consequently, targeting QS is a promising new concept for antimicrobial therapy. However, for this concept to become reality, we must first identify QS systems in pathogenic bacteria, discover the relevant autoinducers and study the underlying regulatory principles. I recently identified a new QS pathway in Vibrio cholerae, the causative agent of cholera disease. The autoinducer of the system is DPO (3,5-dimethylpyrazin-2-ol), a new molecule to biology and the first pyrazine involved in QS. DPO production is widespread among microbes including pathogenic and commensal bacteria. V. cholerae synthesizes DPO from host mucins and our preliminary data show that DPO controls collective phenotypes, such as biofilm formation and toxin production in this major human pathogen. I therefore hypothesize that DPO connects virulence, QS and communication with the host microbiota in V. cholerae and related bacteria. The overarching goal of this project is to understand the roles of DPO in host-microbe interaction and collective behaviours. To this end, we will pursue three key research goals. First, we will study the molecular parameters underlying DPO-signalling and probe the global effects of DPO on gene expression. Second, we will focus on the role of DPO in virulence of V. cholerae and other pathogens. Third, we will probe the effect of DPO on microbial behaviours, such as swarming and biofilm formation. This combined work will provide a comprehensive model for DPO-signalling in bacteria, which will not only advance the fundamental understanding of QS-based communication strategies, but might also provide the framework for QS-inspired anti-infectives.

Mots-clés : quorum sensing,regulatory rnas,biofilms
Projet ERC : READCHINA (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Freiburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

READCHINA is the first broad investigation into the politics and practices of reading in the People’s Republic of China (PRC), their interpretation and their impact on social and intellectual change. The main objective of the study is a reinvestigation of literary history and cultural policy of the PRC from the perspective of the ordinary reader. This grassroots approach is innovative in the writing of Chinese literary history as it means turning away from the established focus on authors and the political context. Instead, READCHINA will investigate the social conditions under which texts were read, what influences this had on the lives of individuals, on social, intellectual and literary change in China, and on the modes of production, distribution and consumption of literature. READCHINA considers the reading of literature as part of a wider web of reading materials, including different media and non-fictional texts. Primary sources will consist among others of archival material, field work interviews, autobiographies, marketing materials, statements by fans in online forums, and literary texts. Combining literary analysis with historical and ethnographical inquiry, as well as methods from the digital humanities, READCHINA will contribute to the fields of literary history and literary sociology. Moreover, in combining close readings of texts with distant reading methods, READCHINA will also foster our understanding of the meaning and impact of popular literature in China and of literary theories on reading. READCHINA will thus bring 20th and 21st century China into the global history of reading – especially so, as practices of reading in China have been shaped by different institutions than in the ‘West’: a Socialist State eager to reform its citizens by means of cultural policies, a centralized bureaucratic system regulating distribution and access to reading matters, and a highly efficient system of media control.

Mots-clés : chinese literature,20th and 21st century literature,history of reading,digital humanities
Projet ERC : RICA (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Vrije Universiteit Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : VU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 338266.5 €

RICA will fundamentally challenge, reconceptualise and redefine core foundational assumptions of the regulatory state. Arm’s length governance and regulatory independence have become the cornerstone normative and institutional design principles of the European regulatory state. Regulatory credibility is premised on agency insulation from politics with major systemic implications in the form of a rise in non-majoritarianism and a parallel devaluation of the political process. Efforts to compensate through alternative sources of input legitimacy have proven challenging. Conceptualised in a rational-choice tradition, accountability is seen to be in a zero-sum relationship with regulatory autonomy. Bolstering accountability is said to threaten autonomy, undermining the system’s normative foundations. Informed by insights from the political science literature on reputation, RICA profoundly questions these assumptions. It does so in two separate and interlocking tracks. Module 1 theorises about, and tests, the established wisdom of a wholesale positive relation between agency insulation and credibility. To the contrary, from a reputational perspective, a strategy of insulation is expected to have a negative effect on regulatory credibility, with overall delegitimising effects. Similarly informed by reputation insights, Module 2 challenges dominant understandings of accountability and puts forward the building blocks of a new theory of public accountability. The module draws out and studies empirically how reputation shapes the accountability behaviour of regulatory actors, both account-holders and account-givers, and their interactions. It will re-conceptualise the role played by accountability in the regulatory state as well as its relationship with autonomy. In contrast to dominant understandings, as a mechanism of reputation-building, accountability can reinforce autonomy with sweeping implications for regulatory control strategies and institutional design choices.

Mots-clés : regulation,agencies,accountability,independence,reputation,control,agencification,credible commitment,regulatory credibility,regulatory state,voluntary accountability
Projet ERC : RICA (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1106585.5 €

RICA will fundamentally challenge, reconceptualise and redefine core foundational assumptions of the regulatory state. Arm’s length governance and regulatory independence have become the cornerstone normative and institutional design principles of the European regulatory state. Regulatory credibility is premised on agency insulation from politics with major systemic implications in the form of a rise in non-majoritarianism and a parallel devaluation of the political process. Efforts to compensate through alternative sources of input legitimacy have proven challenging. Conceptualised in a rational-choice tradition, accountability is seen to be in a zero-sum relationship with regulatory autonomy. Bolstering accountability is said to threaten autonomy, undermining the system’s normative foundations. Informed by insights from the political science literature on reputation, RICA profoundly questions these assumptions. It does so in two separate and interlocking tracks. Module 1 theorises about, and tests, the established wisdom of a wholesale positive relation between agency insulation and credibility. To the contrary, from a reputational perspective, a strategy of insulation is expected to have a negative effect on regulatory credibility, with overall delegitimising effects. Similarly informed by reputation insights, Module 2 challenges dominant understandings of accountability and puts forward the building blocks of a new theory of public accountability. The module draws out and studies empirically how reputation shapes the accountability behaviour of regulatory actors, both account-holders and account-givers, and their interactions. It will re-conceptualise the role played by accountability in the regulatory state as well as its relationship with autonomy. In contrast to dominant understandings, as a mechanism of reputation-building, accountability can reinforce autonomy with sweeping implications for regulatory control strategies and institutional design choices.

Mots-clés : regulation,agencies,accountability,independence,reputation,control,agencification,credible commitment,regulatory credibility,regulatory state,voluntary accountability
Projet ERC : RNAEDIT (Horizon 2020, appel 2014, Consolidator 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 : 1839172.5 €

RNA editing is a type of programmed RNA sequence alteration that can result in a range of proteomic changes, from subtle fluctuations in output, to specific alterations in protein content. Editing is catalyzed by two classes of deaminases: those which convert adenosine to inosine (ADARs) and those which convert cytosine to uracil (APOBEC1). We have previously shown that APOBEC1-catalyzed editing in the transcriptome of macrophages leads to the generation of populations that are heterogeneous, and functionally diverse, enabling rapid population adaptation to different environmental settings. Our first aim for this proposal is to extend our studies to additional immune cell subsets, focusing on cells that are recently recognized as "plastic" to define the contribution of editing to this plasticity of fate and function. RNA editing of the type we study has also been demonstrated to be crucial for cancer progression. For instance, APOBEC1-deficiency significantly reduces tumour burden on cells of the intestine and colon that are prone to adenocarcinomas in the context of the APC-min mutation. This is also the case for testicular carcinomas in mouse models of such tumours. Thus, there is genetic evidence for a requirement for APOBEC1 and RNA editing to drive tumour progression, in two tumour contexts. Based on these data and on our recently deciphered role for APOBEC1 as a "stealthy" diversifier of cellular transcriptomes (and proteomic outcomes), we hypothesize that APOBEC1 drives tumour progression by editing select transcripts in tumour cells (or tumour stem cells), thus enabling the rapid adaptation of the tumour to the onslaught of the immune response. Our second aim is to characterize the subset of edited transcripts in these model tumours (either at the population or at the single cell level) and understand their role to tumour survival and progression, both in mouse models of disease, and in human tumour samples (in collaboration with QP Hammarstrom, KI).

Mots-clés : innate immunity
Projet ERC : RNAEDIT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Karolinska Institutet — Pays : Suède — Rôle : Partner
Acronyme de l'entité : KI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 430827.5 €

RNA editing is a type of programmed RNA sequence alteration that can result in a range of proteomic changes, from subtle fluctuations in output, to specific alterations in protein content. Editing is catalyzed by two classes of deaminases: those which convert adenosine to inosine (ADARs) and those which convert cytosine to uracil (APOBEC1). We have previously shown that APOBEC1-catalyzed editing in the transcriptome of macrophages leads to the generation of populations that are heterogeneous, and functionally diverse, enabling rapid population adaptation to different environmental settings. Our first aim for this proposal is to extend our studies to additional immune cell subsets, focusing on cells that are recently recognized as "plastic" to define the contribution of editing to this plasticity of fate and function. RNA editing of the type we study has also been demonstrated to be crucial for cancer progression. For instance, APOBEC1-deficiency significantly reduces tumour burden on cells of the intestine and colon that are prone to adenocarcinomas in the context of the APC-min mutation. This is also the case for testicular carcinomas in mouse models of such tumours. Thus, there is genetic evidence for a requirement for APOBEC1 and RNA editing to drive tumour progression, in two tumour contexts. Based on these data and on our recently deciphered role for APOBEC1 as a "stealthy" diversifier of cellular transcriptomes (and proteomic outcomes), we hypothesize that APOBEC1 drives tumour progression by editing select transcripts in tumour cells (or tumour stem cells), thus enabling the rapid adaptation of the tumour to the onslaught of the immune response. Our second aim is to characterize the subset of edited transcripts in these model tumours (either at the population or at the single cell level) and understand their role to tumour survival and progression, both in mouse models of disease, and in human tumour samples (in collaboration with QP Hammarstrom, KI).

Mots-clés : innate immunity
Projet ERC : PATHORISC (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : PI
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1987811.0 €

RNA silencing relies on small RNAs that act in RNA induced silencing complexes (RISCs). RISCs use base pairing to select mRNAs or invading nucleic acids such as viruses for repression. RNA silencing may facilitate gene expression changes, for example in host-pathogen interactions. Such changes require reprogramming of RISC, since a different set of RNAs must be rapidly repressed upon pathogen perception. RISC reprogramming is non-trivial: new small RNAs must be produced and be rapidly incorporated into RISC, while unwanted repression by pre-existing RISCs must be eliminated. This project focuses on understanding three central aspects of RISC reprogramming in plant-pathogen interactions. First, we will define mechanisms that allow invading RNA, but not self-RNA, to engage in positive feedback loops for small RNA synthesis, and we will investigate the specific importance of these positive feedback loops in antiviral defense. Second, we will explore how rapid proteolysis of the central RISC component ARGONAUTE1 (AGO1) governs rapid incorporation of newly synthesized small RNA. We will also explore the hypothesis that non-RNA bound AGO1 is degraded to minimize vulnerability to pathogens that use small RNAs as virulence factors to repress host immune signaling. The relevance of these mechanisms of AGO1 proteolysis in plant immunity will be investigated. These studies take advantage of our recent discovery of proteins required specifically for turnover of AGO1. Finally, we explore the hypothesis that rapid chemical modification of mRNA by N6-adenosine methylation (m6A) may bring mRNAs with poor small RNA binding sites under RISC repression. This scenario is supported by interactions between m6A reader proteins and AGO1 discovered in current work in the group. This mechanism may enable reprogramming of RISC specificity rather than composition upon pathogen perception. Our project will fill gaps in knowledge on RNA silencing and elucidate their importance in plant immunity.

Mots-clés : rna silencing,arabidopsis,plant pathogen interaction
Projet ERC : REpiReg (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Friedrich Miescher Institute — Pays : Suisse — Rôle : PI
Acronyme de l'entité : FMI
Type d'entité : Recherche
Financement ERC de l'entité : 1998557.0 €

RNAi refers to the ability of small RNAs to silence expression of homologous sequences. A surprising link between epigenetics and RNAi was discovered more than a decade ago, and I was fortunate enough to be involved in this exciting field of research from the beginning. It is now well established that endogenous small RNAs have a direct impact on the genome in various organisms. Yet, the initiation of chromatin modifications in trans by exogenously introduced small RNAs has been inherently difficult to achieve in all eukaryotic cells. This has sparked controversy about the importance and conservation of RNAi-mediated epigenome regulation and hampered systematic mechanistic dissection of this phenomenon. Using fission yeast, we have discovered a counter-acting mechanism that impedes small RNA-directed formation of heterochromatin and constitutes the foundation of this proposal. Our goal is to close several knowledge gaps and test the intriguing possibility that the suppressive mechanism we discovered is conserved in mammalian cells. We will employ yeast and embryonic stem cells and use cutting-edge technologies (i.e., chemical mutagenesis combined with whole-genome sequencing, genome editing with engineered nucleases, and single-cell RNA sequencing) to address fundamental, as yet unanswered questions. My proposal consists of four major aims. In aim 1, I propose to use proteomics approaches and to perform yeast genetic screens to define additional pathway components and regulatory factors. Aim 2 builds on our ability to finally trigger de novo formation of heterochromatin by synthetic siRNAs acting in trans, addressing many of the outstanding mechanistic questions that could not be addressed in the past. In Aims 3 and 4, experiments conducted in yeast and mouse cells will elucidate missing fragments critical to our understanding of the conserved principles behind RNAi-mediated epigenetic gene regulation.

Mots-clés : chemical mutagenesis,whole genome sequencing,single cell rna sequencing,chromatin profiling,genome engineering
Projet ERC : ICARO (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : Partner
Acronyme de l'entité : IRCCS
Type d'entité : Recherche
Financement ERC de l'entité : 112500.0 €

Radio and chemotherapy are the major clinical treatments for cancer. However these treatments lack cell specificity and can have severe side effects against healthy cells, especially when used in combination. My goal is to develop a nanocrystal (NC) platform to merge radio and chemotherapy into a single entity that is more specific towards tumor cells. To achieve ICARO’s goal, three main objectives will be pursued. The first objective is to introduce post-synthesis reactions, namely cation exchange (CE) and intercalation (INT) reactions, as new protocols to replace or intercalate cations that are useful as radionuclides within the crystal lattice of water-soluble NCs. Our goal is to establish protocols for the preparation of radiolabelled-NCs that will be easily translated to the medical practice for radiotherapy. This requires CE/INT reactions that occur in aqueous media, possibly with NCs prefunctionalized with specific recognition molecules to achieve targeted radiotherapy. To minimize the radio exposure of the operator, CE/INT protocols will be carried out as the last step of NC preparation. The second objective of ICARO will be to explore in situ CE/INT reactions with NCs entrapped in a matrix that simulates the tumor mass. By first located NCs at the tumor and then let the CE/INT to occur, enhance therapeutic effect is expected. The third objective of ICARO will be to develop heterostructures to combine radio and chemotherapy. They will include at least one semiconductor NC on which to perform radiolabelling protocols and one portion made of a superparamagnetic (SP) NC for magnetically triggered drug release. With respect to magnetic hyperthermia, which exploits SP-NCs to produce bulk heat (>46°C) at the tumor, the local heat effect generated at the surface of SP-NCs will enable drug release using a lower dose of magnetic material. Finally, new types of heterostructures combining radio and chemotherapy will be tested, for the first time, in preclinical trials.

Mots-clés : chemotherapy,metal based internal radiotherapy,nanostructures,drug release,nanocarriers,drug delivery,radiolabelled nanoparticles
Projet ERC : AmpliFISH (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université de Strasbourg — Pays : France — Rôle : PI
Acronyme de l'entité : UNISTRA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Rapidly expanding field of cancer diagnostics generates strong demand for new biosensing tools. In particular, it concerns probes for fluorescence in situ hybridization (FISH), that enables detection of DNA and RNA cancer biomarkers directly in diseased cells. Although FISH technique has already been accepted for cancer diagnostics in clinics, its applications are still limited because the method is slow, expensive and requires complicated amplification protocols to obtain sufficient fluorescence signal. Here, we propose a solution based on ultrabright DNA-functionalized dye-loaded fluorescent polymeric nanoparticles recently developed within the ERC grant BrightSens and protected by two patent applications. We aim to develop ultrabright FISH probes (nanoprobes) for cancer research and clinical diagnostics. These nanoprobes will feature single-molecule DNA/RNA sensitivity, low cost, fast and direct one step cell staining protocol, and compatibility with clinical samples and single-cell assays. The amplification of FISH performance will be ensured by our dye-loaded polymeric nanoparticles of 7-20 nm size that are ~1000 fold brighter than single organic dyes. The project is composed of five tasks: (1) Synthesis and optimization of FISH nanoprobes; (2) validation of FISH nanoprobes in cancer cell lines; (3) development of multiplexing assays for detection at least 9 biomarkers; (4) their validation in clinically relevant samples; and, finally, (5) commercialization of FISH nanoprobes. The developed probes will constitute highly competitive products that can greatly improve performance of FISH assays in clinics and research laboratories and thus impact human health. Therefore, they will be directly proposed for commercialization by licensing to existing companies and/or through creation of a startup.

Mots-clés : fluorescent nanoparticles,polymeric nanoparticles,nucleic acids,fluorescence in situ hybridization,fluorescent probes,detection of cancer biomarkers