Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : INJURMET (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Universität Hamburg — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UHH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499985.0 €

Background: Blood-borne metastasis of malignant cells from the primary lesion to distant organs is the major cause of cancer-related death. Most cancer patients face tissue injury at initial diagnosis when tumor tissue is obtained by biopsies to secure the diagnosis of cancer and at primary surgery required to remove the primary tumor. Objectives: We will evaluate whether tissue injury contributes to a significant blood-borne dissemination of viable tumor cells, which is one of the most under-investigated areas in cancer research. We will focus on the two most frequent malignancies in women (breast cancer) and men (prostate cancer) that occur in the in European Union with incidence rates of 139.5 and 139.0 cases per 100,000, respectively. The current project will study the extent of the release of tumor cells into the blood circulation after needle tissue biopsies and primary surgery, the characteristics of the released tumor cells and the contribution of this release to cancer progression. Moreover, we will assess therapeutic strategies to block extravasation of circulating tumor cells (CTCs) to distant sites. As experimental approach, we will apply novel technologies for capturing CTCs and for determining their molecular characteristics in cancer patients as well as experimental models that are able to determine the functional properties of CTCs. Impact: The results will have an important impact on medical practice. If biopsies would contribute to tumor progression, it might be a strong driving force for the development of better imaging modalities or “liquid biopsy” assays of peripheral blood that can diagnose cancer through the detection of CTCs or tumor cell products such as circulating nucleic acids (DNA, microRNA), exosomes or tumor-educated platelets. Moreover, short-term pharmacologic inhibition of extravasation might be able to prevent the extravasation of injury-released CTCs and reduce the risk of metastasis.

Mots-clés : liquid biopsy,tissue injury,breast cancer,prostate cancer,circulating tumor cells,blood,single cell analysis,precision medicine
Projet ERC : COSMIC (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1345000.0 €

Background: One of the major challenges for malaria control and elimination is the phenomenally efficient spread of malaria through sexual stage malaria parasites (gametocytes). The epidemiology and dynamics of gametocytes are poorly understood: it is presently unknown when commitment to gametocytes first occurs during infections and what intrinsic or extrinsic factors influence gametocyte production and infectivity to mosquitoes. I hypothesize that continuous early commitment to gametocyte production and the preferential sequestration of mature gametocytes in the subdermal vasculature are key to explaining the high efficiency of malaria transmission. Aim: This proposal has three main aims: i) to determine when commitment to gametocyte production first occurs during experimental and natural infections; ii) to delineate environmental triggers that stimulate gametocyte production in the absence and presence of treatment; iii) to quantify the differential distribution of parasite developmental stages in different compartments of the human bloodstream. Approach: We will use novel parasite stage composition assays in combination with epidemiological methods to determine the dynamics of gametocyte commitment and maturation during controlled malaria infections in malaria-naive volunteers and during naturally acquired malaria infections in cohorts exposed to malaria in Burkina Faso. A stage-specific immunohistochemistry assay will, for the first time, directly quantify malaria stage composition in the subdermal vasculature and mosquito bloodmeals and allow comparison with other compartments of the circulation. Importance and Innovation: This is the first study to comprehensively characterize gametocyte commitment, maturation and infectivity in experimental and natural infections. This proposal will provide insight in one of the most important questions for malaria elimination: what processes are responsible for the phenomenally efficient transmission of malaria.

Mots-clés : malaria,gametocytes,transmission,infectivity,anopheles,mosquito,sequestration,elimination
Projet ERC : IndiviStat (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Helsinki — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2211564.75 €

Background: Statins are essential drugs in the treatment of hypercholesterolaemia and are among the most prescribed drugs worldwide. The response to statin therapy varies widely between individuals. While most patients show good efficacy, a significant proportion of individuals show poor or even a lack of cholesterol-lowering efficacy. Moreover, a number of patients experience adverse drug reactions. These together with the lack of immediate effect on well-being likely explain the relatively poor adherence to statin therapy. Poor adherence to statins in turn increases the incidence of cardiovascular events and mortality. Aims: The objectives of this project are 1) to develop a systems pharmacology model for predicting statin efficacy and tolerability at the level of an individual patient and 2) to investigate whether selecting the statin based on the model improves treatment adherence. Methods: A systems pharmacology approach will be used to integrate data from in vitro and clinical studies. Semi-physiological pharmacokinetic-dynamic-toxicologic models will be built for each statin allowing the prediction of the pharmacokinetic and clinical outcomes for patients with different characteristics, genotypes, and concomitant medications. The ability of the systems pharmacology algorithm to enhance adherence will be investigated in a randomized clinical trial. Significance: Systems pharmacology models have been increasingly applied in drug development, for example to predict the effect of organ dysfunction on pharmacokinetics. The proposed project is the first to use systems pharmacology predictions to guide clinical drug therapy, thus going beyond the state of the art. If successful, the project will not only improve the prevention and treatment of cardiovascular disease, but it will open new horizons to individualizing drug therapies.

Mots-clés : pharmacogenomics,pharmacokinetic modelling,statin,systems pharmacology
Projet ERC : CleverGenes (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Eastern Finland — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UEF
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2437500.0 €

Background: Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) has great potential to become a novel, minimally invasive new treatment for a large number of patients with severe myocardial ischemia. However, this requires development of new technology. Advancing state-of-the-art: We propose a paradigm shift in gene therapy for chronic ischemia by activating endogenous VEGF-A,-B and -C genes and angiogenic transcription programs from the native promoters instead of gene transfer of exogenous cDNA to target tissues. We will develop a new platform technology (endogenetherapy) based on our novel concept of the release of promoter pausing and new promoter-targeted upregulating short hairpinRNAs, tissue-specific superenhancerRNAs activating specific transcription centers involving gene clusters in different chromosomal regions, small circularRNAs formed from self-splicing exons-introns that can be regulated with oligonucleotides and small molecules such as metabolites, nuclear RNAi vectors and specific CRISPR/gRNAmutatedCas9-VP16 technology with an ability to target integration into genomic safe harbor sites. After preclinical studies in mice and in a newly developed chronic cardiac ischemia model in pigs with special emphasis on the analysis of clinically relevant blood flow, metabolic and functional outcomes based on MRI, ultrasound, photoacoustic and PET imaging, the best construct will be taken to a phase I clinical study in patients with severe myocardial ischemia. Since endogenetherapy also involves epigenetic changes, which are reversible and long-lasting, we expect to efficiently activate natural angiogenic programs. Significance: If successful, this approach will begin a new era in gene therapy. Since there is a clear lack of technology capable of targeted upregulation of endogenous genes, the novel endogenetherapy approach may become widely applicable beyond cardiovascular diseases also in other areas of medicine and biomedical research.

Mots-clés : non coding rnas,cardiovascular diseases,vectors,angiogenesis,ischemia,vascular endothelial growth factors,promoter pausing,targeted integration,rnai,clinical trial
Projet ERC : REJUVENATION (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499995.0 €

Background: To bypass hardware-related complication there have been substantial efforts to create biological pacemakers. Effective strategies have been identified and are now being refined for delivery of long-term function and clinical application. Yet, currently developed biological pacemakers only provide pacing to atrium or ventricle thereby aiming at ~20% of pacemaker patients. To unleash the full potential of biological pacing, targeting virtually every pacemaker patient, effective repair of atrio-ventricular (AV) conduction is crucial. With the arrival of advanced stem cell-based therapies, now is the time to meet this important challenge. Objective: To develop a stem cell-based therapy that restores impulse formation and conduction at the interface between atrium and ventricle. Approach: Human induced pluripotent stem cells (hiPSCs) will be used to produce cells with hallmark features of AV nodal cells. After in vitro testing, these cells will be implanted in vivo (together with biomaterials) to form AV bypass tracts in sheep that are in permanent AV block. In this setting, approaches will be tested for their ability to bridge electrical activity from the atrium to ventricle and protect the ventricle from atrial tachycardia. The final steps of this project focuses on the development of dedicated implantation catheters (in collaboration with Medtronic) and optimization of cellular constructs that are regulatory compliant and ready for clinical testing. Impact: By developing novel therapies to re-establish AV impulse formation and conduction I will broaden the application area of biological pacing to nearly all patients. In Europe ~300.000 pacemakers are implanted annually representing cots of ~8 billion Euros. Five per cent of these implantations result in serious complications requiring re-implantation or other invasive treatments. Biological pacemakers are expected to reduce these complications, improve quality of life, and reduce healthcare costs.

Mots-clés : cardiac arrhythmias,biological pacing,av node regeneration
Projet ERC : CellsBox (Horizon 2020, appel 2018, Proof of concept grants)
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149931.0 €

Based on research from ERC CoG HydroSync where we developed both hardware and software approaches to cell imaging, we are in the position to develop translationally a cell culture and imaging unit, with integrated modular hardware and analysis software allowing automated robust performance. This promises to not just significantly bring down the costs for a broad spectrum of cell biology and single cell imaging experiments. It will also make these experiments more reproducible, systematic and easily accessible in standardised fashion. Perhaps most important of all, by designing in an integrated (whilst modular architecture) system all the components of the experiment (optics, mechanics, cell environment and fluids control, cell sample chambers, analysis), we make it possible to rapidly feedback information on the state of the sample into actions by any of the other modules, thus allowing a new space of experimental design. This automation in running the experimental stage of cell biology, microbiology, infectious disease models, early embryo developmental work, etc (i.e. any of the many situations where one aims to follow the properties of individual cells) also aligns to the current revolution triggered by machine and deep learning approaches. We can imagine a day when integrated experimental "CellsBoxes" perform, in a hypothesis-driven optimised and tireless fashion, a battery of experiments that today would simply be inconceivable. This project addresses one of the experimental bottlenecks that still make too much of biological and medical research subject to bias and poor reproducibility, and change the nature of point-of-care cell tissue analysis. It will be disruptive in the current landscape of optical cell imaging, a market > $1bn globally.

Mots-clés : cell imaging,optical microscopy,automation,image analysis
Projet ERC : NeuronAgeScreen (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Foundation for Research and Technology Hellas — Pays : Grèce — Rôle : PI
Acronyme de l'entité : FORTH;ΙΤΕ
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Battling human neurodegenerative pathologies, and their pervasive societal impact, is a global multi-billion Euro enterprise. Ageing is universally associated with marked decrease of neuronal function and higher susceptibility to neurodegeneration. In human populations, this is manifested as an ever-increasing prevalence of devastating neurodegenerative conditions, including Alzheimer’s and Parkinson’s disease, stroke, several ataxias, and other types of dementia. Development of therapeutic interventions against such maladies is becoming a pressing priority. Drug discovery and drug target identification are two intimately linked facets of intervention strategies aimed at effectively combating human disorders. Genes linked to human diseases often function in evolutionary conserved pathways, readily dissected in simple model organisms. Such organisms provide attractive platforms for devising and streamlining efficient drug discovery and target identification methodologies. During the course of the ERC project NeuronAge, we developed a convenient and versatile platform for high-throughput chemical compound screening based on the nematode C. elegans (Nature 521: 525; Nature 490: 213). This innovative platform uniquely combines state-of-the-art microfluidics technologies for imaging and manipulation of neurons in vivo, with the experimental prowess of C. elegans, a highly malleable genetic model, which offers a precisely defined nervous system, two features that are not available in any other organism. We propose to: (1) bring this high-throughput compound screening system to pre-demonstration stage; (2) evaluate its dependability for drug target identification and drug discovery; (3) file US and European patent applications for IPR protection; and (4) identify potential commercialization opportunities. The overarching aim is to facilitate the exploitation of the innovation generated in the context of NeuronAge towards the betterment of human health and quality of life.

Mots-clés : ageing,caenorhabditis elegans,drug screening,microfluidics,neurodegeneration,pathophysiology,pharmaceutical compound,therapeutic intervention strategies
Projet ERC : HOPE (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Innsbruck Medical University — Pays : Autriche — Rôle : PI
Acronyme de l'entité : MUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2484325.0 €

Because of its biological complexity, cancer is still poorly understood. Chronic inflammation has been shown, both experimentally and epidemiologically, to be a predisposition to, and also an inseparable aspect of clinically prevalent cancer entities. Therefore, a detailed understanding of both tumour and immune cell functions in cancer progression is a prerequisite for more successful therapeutic startegies. My team was the first to reveal the lymphocyte-intrinsic PKC/NR2F6 axis as an essential signalling node at the crossroads between inflammation and cancer. It is the mission of this project to identify molecular signatures that influence the risk of developing tumours employing established research tools and state-of-the-art genetic, biochemical, proteomic and transcriptomic as well as large scale CRISPR/Cas9 perturbation screening-based functional genomic technologies. Defining this as yet poorly elucidated effector pathway with its profoundly relevant role would enable development of preventive and immune-therapeutic strategies against NSCLC lung cancer and potentially also against other entities. Our three-pronged approach to achieve this goal is to: (i) delineate biological and clinical properties of the immunological PKC/NR2F6 network, (ii) validate NR2F6 as an immune-oncology combination target needed to overcome limitations to "first generation anti-PD-1 checkpoint inhibitors" rendering T cells capable of rejecting tumours and their metastases at distal organs and (iii) exploit human combinatorial T cell therapy concepts for prevention of immune-related adverse events as well as of tumour recurrence by reducing opportunities for the tumour to develop resistance in the clinic. Insight into the functions of NR2F6 pathway and involved mechanisms is a prerequisite for understanding how the microenvironment at the tumour site either supports tumour growth and spread or prevents tumour initiation and progression, the latter by host-protective cancer immunity.

Mots-clés : nsclc lung carcinoma,tumour immunity,cd4  and cd8  effector t cells,orphan nuclear receptor nr2f6,intracellular immune checkpoint,innovative immune based human cancer therapy regimen
Projet ERC : ultraRNAs (Horizon 2020, appel 2020, Proof of concept 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 : 150000.0 €

Beet Yellows Virus (BYV) is one of the most destructive pathogens, causing Virus Yellows disease that underlies up to 50% yield losses in sugar beet. The recent regulatory ban on the use of neonicotinoid pesticides in EU has worsened the damage to the EU sugar beet industry. Given the urgency of the current problem caused by BYV, we propose to take advantage of a molecular biological approach to employ small molecular inhibitors called “artificial small interfering RNAs” (art-siRNAs), and demonstrate their ability to specifically bind to and deactivate BYVs within the plants. Our proposal substantially builds on fundamental research outputs from ERC Starting Grant GA680324. We aim to design art-siRNAs that are based on in vivo RNA structure features of BYV RNAs in sugar beet plants and demonstrate high efficacy in virus cleavage or degradation. We will comprehensively assess and validate the effectiveness, efficiency and safety of our structure-based designed art-siRNAs (ultraRNAs) within the laboratories, glasshouses and in-field. We envisage that our art-siRNAs will be applied to sugar beet seed pellets and will be taken up by the seedlings as they grow. When BYV infects these treated plants, we anticipate that our art-siRNAs will bind to the BYV RNA strands and deactivate them, preventing disease. We are confident that through this Proof of Concept we will be able to demonstrate the high performance of our ultraRNAs in terms of not only achieving high efficacy of BYV degradation, but also significantly reducing the quantity of art-siRNAs needed, ideal for incorporating into the seed coating. Ultimately, through follow-on work, our ambition is to provide sugar beet growers with an environmentally-friendly, safe, reliable, efficient, sustainable and long-lasting protection against the virus. Our proposed solution will help save the viability of the sugar beet industry within Europe, which contributes €15.6 billion to the GDPs of the EU-27.

Mots-clés : rna structure,sugar beet,beet virus,artificial small interfering rnas  art sirnas,structure based design