Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : HOLDING-HANDS (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Basel — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1744921.0 €

Breast cancer is the most common cancer in women, resulting in as many as 500000 deaths per year worldwide. Patients with breast cancer die unequivocally because of the development of incurable distant metastases and not because of symptoms related to the primary site. Understanding the complex, yet fundamental mechanisms driving breast cancer metastasis is critical to develop therapies tailored to this disease. The current understanding of how metastasis occurs is derived primarily from mouse models and largely dominated by the notion that single migratory cancer cells within the primary tumor can actively disseminate to distant sites and develop as metastatic deposits. Unexpectedly, our very recent study on patient blood samples has shown that cancer cell groupings, held together through strong cell-cell junctions, can break off the primary tumor and form a metastatic lesion up to 50 times more efficiently than single migratory cancer cells (Aceto et al, Cell, 2014). These findings lead to new open questions, yet highlight a previously unappreciated and targetable mechanism of cancer dissemination. Our preliminary data suggest that, among all types of cell-cell junctions, desmosomes and tight junctions are involved in this process, and therefore represent unprecedented options for developing a metastasis-tailored therapy for breast cancer. The two predominant goals of this proposal are: first, to define the role of specific desmosome (DSG2) and tight junction (CLDN3 and TJP2) components in the development of metastasis. Second, to address their involvement in cellular signaling and response to therapy. These studies will not only use our first-of-a-kind in vivo models developed from patients with breast cancer metastases, but also cross the boundaries between basic science and clinical applications. Our research has the long-term ambition to lead to a novel class of therapeutic agents tailored to block cell-cell junctions and prevent metastatic spread of cancer.

Mots-clés : metastasis,breast cancer,mouse models
Projet ERC : ULTIMA (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : European Organization for Nuclear Research — Pays : Suisse — Rôle : PI
Acronyme de l'entité : CERN
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Breast cancer is the most common cause of death among women. For lowering the mortality rates and improving life quality, it would be beneficial to diagnose and treat diseases early. Dedicated Positron Emission Tomography (PET) application Positron Emission Mammography (PEM) has been developed for functional medical imaging of specific breast cancer biomarkers. PEM enables accurate detection of small malignant tumors at an earlier stage. However, it suffers from major limitations on becoming suitable for general screening purposes. One of the limitations is that the process exposes the patients to relatively high ionizing radiation doses causing poor total risk-benefit ratios. The project addresses this challenge and contributes to providing safe oncology screening possibilities available for larger patient-base. This project will demonstrate the proof of concept of a state-of-the-art nuclear imaging innovation, which will enable the detection of energy deposition with significantly improved energy and time resolution levels of a PET application. Our approach features high quality pictures with considerably lower radio-tracer dose levels than the current commercial scanners. This is enabled by an order of a magnitude improvement in the signal-to-noise ratio over the current time-of-flight PET scanners. The innovation comprise a novel combination of scintillating and photonic crystals for an improved light output efficiency and fast electronics. As a complementing technology to PEM imaging system, it contributes to safer cancer scanning modality while shortening the scanning process. This results to improved process throughput and vast socio-economic benefits. Within the project, the imaging system technical performance will be benchmarked to a dedicated medical imaging application, such as PEM. The project also addresses the commercialisation considerations, economical feasibility and assesses the system cost. The project will be carried out in close collaboration with a potential exploitation entity.

Mots-clés : proof of concept,commercialisation,scintillating photonic crystal,patterning,high light output,high timing resolution,positron emission tomography,mammography,low dose,oncology screening
Projet ERC : p38Cure (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Institute for Research in Biomedicine — Pays : Espagne — Rôle : PI
Acronyme de l'entité : IRB;IRB-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 149995.0 €

Breast tumors are classified by several grading systems and divided into four main molecular subtypes: Luminal A, Luminal B, Triple negative/basal-like and HER2+. Since luminal A tumors tend to be ER+, their treatment often includes hormonal therapy. HER2+ tumors can be treated with Trastuzumab, an anti-Her2 receptor antibody. Hormonal therapies or Trastuzumab cannot be used for triple negative tumors, which are ER- and HER2-, and these are usually treated with a combination of surgery, radiotherapy and chemotherapy. There is an urgent need for new therapies to effectively treat different breast cancer subtypes. Translating basic knowledge on tumor cell biology into more effective diagnostic tools and improved treatments for patients remains difficult. The use of patient-derived xenografts (PDX) as preclinical models that recapitulate the complexity and heterogeneity of the human tumors should help to develop and successfully translate to the clinic new therapies. Our recent work provides genetic and pharmacological evidence showing that p38 MAPK inhibition cooperates with the chemotherapeutic agent cisplatin to reduce breast tumor size and malignancy in vivo. Our results support a potential therapeutic use for p38 MAPK inhibitors in combination with chemotherapeutic drugs. The idea is to use PDX of specific breast cancer subtypes for preclinical validation of a new drug combination therapy with potential benefit to patients, which can be confirmed in clinical trials.

Mots-clés : breast cancer therapy
Projet ERC : DISTRACT (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
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 : 2476790.0 €

Bridging anthropology, sociology, economics, psychology, political science, and data science, DISTRACT combines advanced data science tools and established social science analysis to explore a pressing challenge: the ever more alluring distractions of human attention in the age of smartphones and other digitized technologies. DISTRACT departs from five linked hypotheses: 1) The attention is commonly (by scholars and laymen) seen as finite; ⇒ (2) As such, it is a scarce resource that is subject to competition and regulation; ⇒ 3) This is not new but it is acquiring unseen urgency in the current data economy; ⇒ 4) An interdisciplinary social data science approach allows for solid and novel investigation of this unmet scientific and societal need; and ⇒ 5) As the world’s most digitized country (and homogeneous population and state-of-the-art public databases), Denmark is an ideal site to study this political economy of distraction. Combining qualitative and quantitative data from four case studies, DISTRACT thus aims to trace and analyse the mental, social and material techniques by which attention is captured, retained and deflected in digitized Denmark. Analytically, we distinguish between three layers in which attention is managed and manipulated: a “mental”, “social” and “material” dimension. We also differentiate between three components of given attention/distraction sequence: the ‘”capturing”, “retention” and “deflection” phase. Empirically, case-studies shall be carried out of (a) national politics, (b) the tech business, (c) “off-the-grid” alternative communities, and (d) education and workplace environments. Data shall be collected, integrated and analysed via a combination of 1) qualitative methods, including ethnographic fieldwork and semi-structured interviews and discourse analysis; (2) quantitative methods, including natural experiments and predictive models; and (3) quali-quantitative methods including web scraping and supervised machine learning.

Mots-clés : attention economy,quali quantitative methods,social data science,interdisciplinarity,big data,data economy,digitization,social media,ethnography,digital methods,data ethics,topic modelling,denmark,europe
Projet ERC : TOPOLOGICAL (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Birmingham — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997599.96 €

By using metamaterials and metasurfaces as the platform, this proposal focuses on the novel topological physics and applications introduced by Berry phase. The flexibility in engineering the artificial ‘atoms’ and ‘molecules’ of metamaterials provides unlimited possibilities to create new structural effect where symmetry (or symmetry breaking) and topology play critical roles. We are particularly interested in the role Berry phase plays in various nontrivial surface optical effects, including topological surface states and spin Hall effect of light. The investigation of the scattering immune surface states in a topological metamaterial, i.e. an effective medium approach, acts to unify the spin Hall effect of light with the more unconventional scheme of topological orders and protected surface states. We will further exploit Berry phase in the nonlinear regime, in particular harmonic generations, to control the nonlinear coefficients to an unprecedented level. Hence our study on Berry phase in the nonlinear regime will point to a new research direction on nonlinearity coefficient engineering, which will have important impact in the area of nonlinear optics. The proposal also investigates into practical applications brought by a novel type of geometrical metasurfaces, where the phase and hence the wavefront are finely controlled by the Berry phase in a highly robust manner. The proposal involves the development of innovative synthesis technologies, theoretical analysis, numerical simulations, experimental characterizations, and device development. The new symmetry and topological effects in this research will greatly impact a number of disciplines including material science, condensed matter physics and photonics.

Mots-clés : metamaterials,metasurfaces,plasmonics,topological orders
Projet ERC : corr-DFT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
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 : 1999891.25 €

By virtue of its computational efficiency, Kohn-Sham (KS) density functional theory (DFT) is the method of choice for the electronic structure calculations in computational chemistry and solid-state physics. Despite its enormous successes, KS DFT’s predictive power and overall usefulness are still hampered by inadequate approximations for near-degenerate and strongly-correlated systems. Crucial examples are transition metal complexes (key for catalysis), stretched chemical bonds (key to predict chemical reactions), technologically advanced functional materials, and manmade nanostructures. I aim to address these fundamental issues, by constructing a novel framework for electronic structure calculations at all correlation regimes. This new approach is based on recent formal developments from my group, which reproduce key features of strong correlation within KS DFT, without any artificial symmetry breaking. My results on the exact infinite-coupling-strength expansion of KS DFT will be used to endow that theory with many-body properties from the ground up, thereby removing its intrinsic bias for weak correlation regimes. This requires novel combinations of ideas from three research communities: chemists and physicists that develop approximations for KS DFT, condensed matter physicists that work on strongly-correlated systems using lattice hamiltonians, and mathematicians working on mass transportation theory. The strong-correlation limit of DFT enables these links by defining a natural framework for extending lattice-based results to the real space continuum. On the other hand, this limit has a mathematical structure formally equivalent to the optimal transport problem of mathematics, enabling adaptation of methods and algorithms. The new approximations will be implemented with the assistance of an industrial partner and validated on representative benchmark chemical and physical systems.

Mots-clés : density functional theory,electronic correlations,exchange correlation functionals,mass transportation theory,optimal transport
Projet ERC : FATE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : PI
Acronyme de l'entité : IRCCS
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2390000.0 €

CD8+ T cells have a key role in eliminating intracellular pathogens and tumors that affect the liver. The protective capacity of these cells relies on their ability to migrate to and traffic within the liver, recognize pathogen- or tumor-derived antigens, get activated and deploy effector functions. While some of the rules that characterize CD8+ T cell behavior in the infected and cancerous liver have been characterized at the population level, we have only limited knowledge of the precise dynamics of intrahepatic CD8+ T cell conduct at the single-cell level. In preliminary data for this project we have developed several advanced imaging techniques that allow us to dissect the interactive behavior of CD8+ T cells within the mouse liver at an unprecedented level of spatial and temporal resolution. We predict that this approach, combined with unique models of hepatitis B virus pathogenesis and a new model of hepatocellular carcinoma created ad hoc for this proposal, will generate novel mechanistic insights into the spatiotemporal determinants that govern the capacity of CD8+ T cells to home and function in the virus- or tumor-bearing liver. Specifically, we plan to pursue two main goals: 1) To assess how the anatomical, hemodynamic and environmental cues that characterize hepatocellular carcinomas shape CD8+ T cell behavior and function; 2) To characterize intrahepatic T cell priming events that induce functionally defective T cell responses. Results emerging from these studies will advance our knowledge on how adaptive immunity mediates pathogen clearance and tumor elimination. This new knowledge may lead to improved vaccination and treatment strategies for immunotherapy of infectious diseases and cancer.

Mots-clés : cd8  t cells,intravital imaging,dynamics of immune responses,liver,hepatitis b virus,hepatocellular carcinoma,immunopathology
Projet ERC : CHROMOTOPE (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Sorbonne Université — Pays : France — Rôle : PI
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1280375.0 €

CHROMOTOPE will offer the very first analysis of the changes that took place in attitudes to colour in the 19th century, and notably how the ‘chromatic turn’ of the 1850s mapped out new ways of thinking about colour in literature, art, science and technology throughout Europe. Britain’s industrial supremacy during this period is often perceived through the darkening filter of coal pollution, and yet the industrial revolution transformed colour thanks to a number of innovations like the invention in 1856 of the first aniline dye. Colour thus became a major signifier of the modern, generating new discourses on its production and perception. This Victorian ‘colour revolution’, which has never been approached from a cross-disciplinary perspective, came to prominence during the 1862 International Exhibition – a forgotten, and yet key, chromatic event which forced poets and artists like Ruskin, Morris and Burges to think anew about the materiality of colour. Rebelling against the bleakness of the industrial present, they invited their contemporaries to learn from the ‘sacred’ colours of the past – a ‘colour pedagogy’ which later shaped the European arts and crafts movement. Building on a pioneering methodology, CHROMOTOPE will bring together literature, visual culture, the history of sciences and techniques and the chemistry of pigments and dyes, with high-impact outcomes, including one major exhibition at the Ashmolean Museum, a thorough pigment analysis of Burges’s Great Bookcase and the creation of an online database of 19th century texts on colour. This project will not only give invaluable insight into hitherto neglected aspects of 19th century European cultural history, it will also reveal the central role played by chromatic materiality in the intertwined artistic and literary practices of the period. This will in turn change the way the relationships between text and image, as well as the materiality of the text itself, may be envisaged in literary studies.

Mots-clés : colour,polychromy,pigments,dyes,chemistry of colour,victorian literature and painting,arts and crafts,material studies,text and image studies,reception studies,gender studies
Projet ERC : ToDL (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499974.51 €

Can we synthesise life de-novo in the lab? This is one of the Grand Challenges of contemporary Science. Overall objective of this project is to set important steps in turning chemistry into biology by building fully synthetic chemical systems that contain and integrate some of the essential elements of life: replication, metabolism and compartmentalisation. Functional coupling of any of life’s essential elements has not been achieved, at least not without making use of biomolecules. We now aim to achieve such coupling and develop fully chemical systems to become increasingly life-like. Specific aims are: 1. Achieve and explore Darwinian evolution of a fully synthetic system of peptide-based self-replicating molecules. 2. Develop self-replicating molecules that are capable of catalysing not only their own formation, but also other chemical reactions. We will specifically target chemical reactions that result in the production of building blocks which the replicators can utilize to replicate, thereby integrating replication with a rudimentary form of metabolism. 3. Achieve self-reproducing compartments and develop ways to couple replication inside compartments with compartment division. Three parallel approaches will be explored, based on (i) vesicle-type compartments made from self-replicating molecules; (ii) coascervates and (iii) compartments made by surfactants that are produced by catalytically active self-replicators. 4. Extend replication from peptide-based building blocks to ones containing nucleobases. We also plan to investigate reaction networks made from mixtures of peptide- and nucleobase-containing building blocks). 5. Develop kinetic modelling tools that allow an efficient exploration of multi-parameter space of the reaction networks developed in 1-4. Through stochastic computational modelling we will address mechanistic issues that are experimentally intractable. Furthermore, modelling will allow a more efficient exploration of multi-parameter space.

Mots-clés : dynamic combinatorial chemistry,systems chemistry,synthetic life
Projet ERC : CHEMCHECK (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

Cancer evades the immune system by generating an immunosuppressive tumour-microenvironment through various mechanisms to enable unhampered growth. Recent breakthroughs in blocking one of these mechanisms – the so called ‘immune checkpoints’ – put cancer immunotherapy back in the spotlights. Although promising, clinical benefits of these checkpoint inhibitors as single treatment has been limited to a subset of patients and goes along with unwanted systemic autoimmune toxicity. I hypostasize, that attacking the tumour microenvironment from multiple immunological angles simultaneously by local, conditional, and multimodal immunomodulation will greatly improve success of cancer immunotherapy and patient wellbeing. To achieve this, I will develop a highly defined synergistic chemistry-based molecular therapeutic toolbox to specifically attack cancer, acting on effector T cells, macrophages as well as tumour cells simultaneously. In this highly multidisciplinary endeavour I will (i) generate novel multifunctional dendritic cell targeted anti-cancer vaccines to ‘educate’ the patient’s immune system to recognise the tumour, (ii) I will develop conditional, targeted immune checkpoint inhibitors to release the immunosuppressive break specifically within the tumour microenvironment without the risk of autoimmunity and (iii) I will generate chemical tools to locally eliminate the tumour-associated macrophages to tear down a major immunosuppressive barrier. I will do so utilizing the novel ModimAb technology which I developed to obtain functionalized antibody fragments. These individual therapeutic tools will allow me and my research team to explore uncharted tumour immunological territories in vitro as well as in vivo, greatly advancing the field of cancer immunotherapy. But above all, together they will form a highly dedicated symbiotic immunotherapeutic regime which will be extremely effective without systemic side effects, dramatically improving patient care.

Mots-clés : cancer immunotherapy,chemical biology,tumour microenvironment,immune checkpoint,antibody engineering