Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : DrugComb (Horizon 2020, appel 2016, Starting 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 : 1500000.0 €

Making cancer treatment more personalized and effective is one of the grand challenges in our health care system. However, many drugs have entered clinical trials but so far showed limited efficacy or induced rapid development of resistance. We critically need multi-targeted drug combinations, which shall selectively inhibit the cancer cells and block the emergence of drug resistance. This project will develop mathematical and computational tools to identify drug combinations that can be used to provide personalized and more effective therapeutic strategies that may prevent acquired resistance. Utilizing molecular profiling and pharmacological screening data from patient-derived leukaemia and ovarian cancer samples, I will develop model-based clustering methods for identification of patient subgroups that are differentially responsive to first-line chemotherapy. For patients resistant to chemotherapy, I will develop network modelling approaches to predict the most potential drug combinations by understanding the underlying drug target interactions. The drug combination prediction will be made for each patient and will be validated using a preclinical drug testing platform on patient samples. I will explore the drug combination screen data to identify significant synergy at the therapeutically relevant doses. The drug combination hits will be mapped into signalling networks to infer their mechanisms. Drug combinations with selective efficacy in individual patient samples or in sample subgroups will be further translated into in treatment options by clinical collaborators. This will lead to novel and personalized strategies to treat cancer patients.

Mots-clés : drug combinations,personalized cancer medicine
Projet ERC : REUSE4MALARIA (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : University of Lisbon — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 145500.0 €

Malaria is a serious parasitic disease afflicting 198 million people in 2013, with an estimated death toll of approximately 600 000. Approximately half the world’s population is at risk of malaria. So far there is no cure/vaccine against malaria and current chemoprotective treatments have shortcomings, such as: 1) Limited Number of Drugs effective against malaria parasites; 2) Adverse Side Effects (observed in 32% to 44% of users); 3) Parasite Resistance to most of the drugs used for prevention and treatment; and 4) Limited Use (restrictions on age, genetic traits, pregnancy, etc). Our ERC-funded research uncovered a novel mechanism of action that can be targeted for malaria chemoprotection, with fewer side effects and reduced propensity to generate parasite resistance, on which we filed for IP protection. Furthermore, we have identified a set of likely drug candidates already validated in the clinic, which are likely candidates for malaria chemoprotection. In fact, our preliminary data indicates that a known anti-diabetic drug significantly affects parasite growth. We are seeking funding to initiate pre-clinical studies for repurposing this drug for malaria chemoprotection. This PoC funding will allow us to complete the following aims: 1) in vitro profiling to define therapeutic dose for malaria chemoprotection; 2) in vivo profiling to perform efficacy and toxicity studies; 3) further define IP Strategy; 4) draft early stage Regulatory Approval Roadmap; 5) conduct Market Analysis and develop a Business Case.

Mots-clés : malaria,nutrient sensing,chemoprotection treatment,metformin
Projet ERC : BoneMalar (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Glasgow — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2298557.0 €

Malaria remains a major problem of public health in developing countries. It is responsible for about 600000 deaths per year, predominantly children in sub-Saharan Africa. There is an urgent need for novel therapies as resistance against current treatments is widespread. The complex parasite biology requires a multifaceted approach targeting multiple life cycle stages and virulence pathways. The pathogenesis of the most deadly of human malaria parasites, Plasmodium falciparum, is related to the capability of infected red blood cells to sequester in deep tissues. Sequestration is critical for the completion of the red blood cell cycle because the release of parasites into the blood circulation allows recognition by surveillance macrophages and clearance in the spleen. A series of studies have since led to the understanding that sequestration of asexually replicating parasites is caused by the adherence of parasite infected red blood cells to the vascular endothelium of various tissues in the body. We have recently demonstrated that gametocytes, the only stage capable of transmission to the mosquito vector, develop in the extravascular environment of the human bone marrow. Preliminary studies in the mouse model have confirmed this finding and also suggest existence of an asexual reservoir in the bone marrow. In this innovative multidiscipinary proposal we aim to investigate the host pathogen interactions at the interface between infected red blood cell and bone marrow vasculature. Specifically we will focus on the following questions: how do parasites home to bone marrow? What are the changes in the bone marrow endothelium upon infection? How do parasites adhere with and transmigrate across the vascular endothelium in the bone marrow? The proposed studies initiate detailed characterization of a new paradigm in malaria parasite interaction with the host vasculature and provide a compelling new avenue for intervention strategies.

Mots-clés : host pathogen interactions,malaria,pathogen transmission,bone marrow homing,vascular adherence
Projet ERC : CATENA (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Birmingham — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1756928.0 €

Manuscripts which contain commentary alongside the biblical text are some of the most significant and complicated witnesses to the Greek New Testament. First compiled around the fifth century, the commentaries consist of chains of extracts from earlier writers (catenae). These manuscripts became the main way in which users encountered both the text and the interpretation of the New Testament; revised editions produced in the eleventh and twelfth centuries continued to hold the field until the invention of printing. Recent advances have shown that commentary manuscripts play a much more important role than previously thought in the history of the New Testament. The number of known copies has increased by 20% following a preliminary survey last year which identified 100 additional manuscripts. A recent comprehensive textual analysis of the Catholic Epistles indicated that all witnesses from the third generation onwards (some 72% of the total) could stem from the biblical text of three commentary manuscripts occupying a key place in the textual tradition. Investigation of the catena on Mark has shown that the selection of extracts could offer a new approach to understanding the theology of the compilers and the transmission of the commentaries. The CATENA Project will use digital tools to undertake a fuller examination of Greek New Testament commentary manuscripts than has ever before been possible. This will include an exhaustive survey to establish a complete list of witnesses; a database of extracts to examine their principles of organisation and relationships; and electronic transcriptions to determine their role in the transmission of the biblical text. The results will have a direct impact on editions of the Greek New Testament, providing a new understanding of its text and reception and leading to broader insights into history and culture.

Mots-clés : biblical commentary manuscript new testament textual criticism greek catena patristic interpretation
Projet ERC : MagneticMoth (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Lund University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2498625.0 €

Many animals – including birds, sea turtles and insects – perform spectacular long-distance migrations across the surface of the Earth. Remarkably some, like birds, can accurately migrate between highly specific locations thousands of kilometres apart, a navigational feat that requires an external compass cue and a robust sensory system to detect it. The Earth’s magnetic field is one such compass cue. But exactly how the magnetic field is sensed, and which receptor cells are involved, remains a mystery and its discovery is one of the greatest “holy grails” in modern sensory physiology, and also the main aim of this proposal. Fortuitously, I have made a pioneering discovery that a migratory insect – the Australian Bogong moth – relies on the Earth’s magnetic field to navigate at night. Due to its tractable nervous system, this insect may thus hold the key to uncovering the identity of the enigmatic magnetosensor. By tethering flying migrating moths in a flight simulator, I will dissect for the first time how insects use magnetic cues to navigate, isolating which of the two current (contentious) hypotheses for magnetic sensation apply. The most likely of these involves the action of photoreceptor-based cryptochrome (Cry) molecules in the eyes. Having cloned genes for 4 visual opsins and 2 Cry in Bogong moths, I will use in situ hybridisation to localise putative magnetoreceptors in the eyes, targeting them with intracellular electrophysiology and magnetic stimulation in an attempt to describe the physiology of these elusive sensors for the first time. The project is ground breaking since it will elucidate how a migratory insect, despite its small eyes and brain, detects and uses the Earth’s magnetic field for navigation. The discovery of the enigmatic magnetoreceptor would be a sensation, opening the floodgates for international research on this little understood sense.

Mots-clés : insect migration,navigation,magnetic sense,magnetoreceptor
Projet ERC : EPI-Centrd (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Aix-Marseille Université — Pays : France — Rôle : PI
Acronyme de l'entité : amU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1261250.0 €

Many efficient drugs have been designed to treat neurological disorders, but have failed in the clinic because they were toxic, could not cross the blood-brain barrier, and/or had deleterious side effects in healthy regions. I propose a conceptual breakthrough to solve these three issues, with minimally-invasive organic electronic ion pumps (OEIPs) to provide targeted treatment where and when it is needed. I will use epilepsy as the disease model because of its high rate of drug-resistance (30%) and will offer concrete opportunities for clinical transfer of such state-of-the-art technology. The clinical problem: Resective surgery is frequently the last option available to a patient with drug-resistant epilepsy (> 1 million persons in the EU). However, surgery fails in 30% of the cases and can have deleterious consequences with severe postoperative neurological deficits (impaired motor function, speech and memory). Furthermore, some cases of epilepsy are simply untreatable surgically because resective surgery would leave unacceptable damage to core functions. Clearly, a new therapeutic approach is needed when neurosurgery is not possible or deemed too risky. The OEIP solution: As I have demonstrated, OEIPs combine state-of-the-art organic electronics and pharmacology to control epileptiform activity in vitro by directly delivering inhibitory neurotransmitters on-demand. I additionally demonstrated that thin-film flexible organic electronics can be used to create minimally-invasive depth probes for implantation which significantly reduced tissue damage compared to standard rigid implants in vivo. I will integrate OEIPs on such probes creating devices which will have both the high-quality recordings provided by the organic electrodes for electrophysiological seizure detection and the molecular delivery capability of the OEIP for seizure intervention. The devices will be a closed-loop system to detect seizure onset and intervene in the affected brain region.

Mots-clés : bioelectronics,flexible biopolymer,brain medical device,epilepsy
Projet ERC : MesoPhone (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Lancaster University — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2748271.0 €

Many fascinating quantum behaviours occur on a scale that is intermediate between individual particles and large ensembles. It is on this mesoscopic scale that collective properties, including quantum decoherence, start to emerge. This project will use vibrating carbon nanotubes – like guitar strings just a micrometre long – as mechanical probes in this intermediate regime. Nanotubes are ideal to explore this region experimentally, because they can be isolated from thermal noise; they are deflected by tiny forces; and they are small enough that quantum jitter significantly affects their behaviour. To take advantage of these properties, I will integrate nanotube resonators into electromechanical circuits that allow sensitive measurements at very low temperature. First, I will study the motional decoherence of the nanotube itself, by using it as the test particle in a new kind of quantum interferometer. This experiment works by integrating the nanotube into a superconducting qubit, and will represent a test of quantum superposition on a larger mass scale than ever before. It will answer a longstanding question of physics: can a moving object, containing millions of particles, exist in a superposition of states? Second, I will use the nanotube device as a tool to study superfluid helium 3 – the mysterious state of matter that may emulate the interacting quantum fields of the early universe. By measuring an immersed nanotube viscometer, I will be able to measure the behaviour of superfluid excitations on a scale where bulk superfluidity begins to break down. Third, I will add to the device a nanomagnet on nanotube springs, creating an ultra-sensitive magnetic force sensor. This offers a way to perform nuclear magnetic resonance on a chip, ultimately creating a microscopy tool that could image for example single viruses.

Mots-clés : carbon nanotubes,quantum optomechanics,superconducting devices,magnetic resonance
Projet ERC : FORENSICS (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of Mannheim — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UMA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1212934.0 €

Many markets are characterized by illicit or illegal behavior by agents. To the extent that the empirical economic framework does not incorporate these unobserved actions or control for them in estimation, the resulting models are likely to be mis-specified. Naturally, if the models do not contain all elements relevant for decision making, then predictions based on the estimates will be misleading, which could result in incorrect policy recommendations. This project directly addresses three situations in which unobserved behavior plays a crucial role. The first concerns markets where consumers engage in illicit behavior. These markets are prevalent in society as they constitute the market for illicit drugs, which is estimated at more than $300 billion per year (UN, 2012). The second concerns markets where firms make strategic decisions in the presence of an unidentified competitor - a counterfeiter, where the global value of counterfeit products rivals that of illegal drugs (OECD, 2007). The third concerns situations where firms use legal tools for illegal purposes, for which the impact is challenging to quantify and one goal of this project. In each area, the project (i) develops state-of-the-art empirical models that incorporate illicit behaviors, (ii) proposes novel estimation methods that can be used to detect illegal behavior, and (iii) provides evidence that the proposed methodology is feasible and the data are sufficient to estimate the models. Incorporating and estimating unobserved behavior in a variety of settings is an ambitious undertaking. However, it is vital as a key objective of the proposal is to provide policy makers with tangible tools that accurately reflect the unobserved nature of these markets. Given the global significance of illicit markets, the novel concepts proposed, and the focus on policy, this project has the potential to make a sizable impact, both in and beyond academia, representing an ambitious but worthwhile pursuit.

Mots-clés : empirical industrial organization,illicit markets,counterfeit markets,vertical restraints,antitrust and competition policy
Projet ERC : GermlineChrom (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of East Anglia — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : UEA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 108776.61 €

Many multicellular organisms have a division between germline and soma. It has been long-standing dogma that all these cells have the same genome as they develop from a single cell. However, programmed DNA elimination can remove DNA during germline–soma differentiation and thereby lead to dramatic differences in genome organization between tissues. The evolution and function of programmed DNA elimination remains mysterious due to technological limitations and lack of an evolutionary framework. However, a role of this phenomenon in minimizing germline–soma genetic conflict has been suggested. This conflict arises when developmental gene expression is beneficial for the germline but deleterious for the soma. The aim of this proposal is to test whether programmed DNA elimination allows germline-specific expression of developmental genes to minimize germline–soma conflict. Using the germline-restricted chromosome (GRC) of the zebra finch as a unique study system, I have recently pioneered high-throughput genomics to overcome previous limitations. Combining my novel approach with transcriptomics, proteomics, cytogenetics, and developmental and functional genomics will provide unprecedented insights into the evolution and function of germline–soma genome differences. First, I will establish the so far first GRC study system by generating a zebra finch GRC reference assembly. Second, I will test how the GRC is inherited and maintained in zebra finch populations. Third, I will elucidate the long-term evolutionary history of GRCs across songbirds to reveal genes that are most conserved and thus candidates for GRC function. Fourth, I will trace GRC expression and elimination across zebra finch development, and functionally validate candidate genes. Altogether, I will establish an evolutionary framework which will significantly advance our understanding of programmed DNA elimination during germline–soma differentiation, a phenomenon likely widespread across the Tree of Life.

Mots-clés : programmed dna elimination,germline soma genome differences,genetic conflict,molecular cytogenetics,single molecule genomics,comparative genomics,population genomics
Projet ERC : DiaDev (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : King's sierra leone partnership limited by guarantee — Pays : Sierra Leone — Rôle : Partner
Type d'entité : Autres
Financement ERC de l'entité : 26180.35 €

Many people living in resource-poor settings have never had access to the laboratory facilities or technical expertise that are needed to diagnose diseases. With the development and deployment of a new generation of affordable, easy-to-use, and portable diagnostic devices that are designed for places with no laboratory infrastructure, the global landscape of diagnosis is dramatically changing. Can portable diagnostic devices strengthen health systems in resource-poor settings? DiaDev is the first study to comprehensively address this question through comparison across multiple devices, sites of production, and contexts of use. Diagnostic technologies are often championed as universal solutions to health equity and access. This ethnographic study investigates the extent to which how diagnostic devices work and what they can achieve depends on the locally specific relationships through which they are designed and used. Five ethnographic case studies from the USA, India and Sierra Leone examine the partnerships between donors, governments, humanitarian organisations and users that characterise current models of technological innovation and implementation in global health, the processes by which diagnostic devices are integrated with health infrastructures in target settings, and the practices of knowledge production and use they entail. The ultimate aim is to generate new insight into (i) changing relationships of power between governments, donors, and business in global health, and (ii) the ways in which diagnostic devices are transforming health systems in resource-poor settings. It will produce a new context-specific and comparative framework for exploring the opportunities and challenges involved in the design and use of diagnostic devices. Through innovative collaborative methods it will also develop a set of ‘health system strengthening tools’ that will enable stakeholders to improve the design and use of these devices in dialogue with the project findings.

Mots-clés : global health,institutions,partnership,value,humanitarian enterprise