Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ToxoPersist (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Geneva — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIGE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2297606.0 €

Toxoplasma gondii is the most successful obligate intracellular parasites infecting virtually all warm-blooded animals. A infection initiates with the dissemination of the fast-replicating tachyzoites. At the onset of the immune response tachyzoites convert into slow-growing bradyzoites that form cysts in the central nervous system and in striated and heart muscles. Encystation ensures life-long persistence and poses a significant threat of reactivation during immunosuppression and can lead to encephalitis and severe clinical manifestations. Despite the importance of encystation for pathogenesis and transmission, our insight into how T. gondii defies the immune responses to take up permanent residence in the immunocompetent hosts is rudimentary. We propose to determine the molecular mechanisms governing cyst wall formation and parasite adaption to encystation. We will capitalize on the increased sensitivity of -omics approaches, the power of the CRISPR/Cas9 genome editing, the high-resolution microscopy, and on the ex-vivo tissue examination by MALDI imaging mass spectrometry and NanoSIMS technologies.The specific objectives are to: 1. Identify the components of the Cyst Wall (CW), Parasitophorous Vacuole (PV) and PMV Membrane (PVM) of the cyst 2. Determine the parasite factors responsible for CW formation and maturation via targeted and unbiased approaches 3. Define the metabolic network of parasite that is able to initiate encystation and ensure persistence 4. Measure subversion of host metabolic functions by parasite effectors during encystation and persistence We anticipate fundamental discoveries on i) the regulatory and trafficking circuits that govern CW formation as a biological barrier during encystation ii) metabolic adaptation and subversion of host cellular functions during encystation. Ultimately, understanding parasite strategies and versatilities that ensures its parasitism in immunocompetent hosts and bottlenecks as new targets for intervention.

Mots-clés : protein trafficking,host parasite interface,persistence,chronic infection
Projet ERC : CGinsideNP (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Freie Universität Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1486800.0 €

Traditional complexity theory focuses on the dichotomy between P and NP-hard problems. Lately, it has become increasingly clear that this misses a major part of the picture. Results by the PI and others offer glimpses on a fascinating structure hiding inside NP: new computational problems that seem to lie between polynomial and NP-hard have been identified; new conditional lower bounds for problems with large polynomial running times have been found; long-held beliefs on the difficulty of problems in P have been overturned. Computational geometry plays a major role in these developments, providing some of the main questions and concepts. We propose to explore this fascinating landscape inside NP from the perspective of computational geometry, guided by three complementary questions: (A) What can we say about the complexity of search problems derived from existence theorems in discrete geometry? These problems offer a new perspective on complexity classes previously studied in algorithmic game theory (PPAD, PLS, CLS). Preliminary work indicates that they have the potential to answer long-standing open questions on these classes. (B) Can we provide meaningful conditional lower bounds on geometric problems for which we have only algorithms with large polynomial running time? Prompted by a question raised by the PI and collaborators, such lower bounds were developed for the Frechet distance. Are similar results possible for problems not related to distance measures? If so, this could dramatically extend the traditional theory based on 3SUM-hardness to a much more diverse and nuanced picture. (C) Can we find subquadratic decision trees and faster algorithms for 3SUM-hard problems? After recent results by Pettie and Gronlund on 3SUM and by the PI and collaborators on the Frechet distance, we have the potential to gain new insights on this large class of well-studied problems and to improve long-standing complexity bounds for them.

Mots-clés : computational geometry,complexity theory
Projet ERC : ANaPSyS (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Konstanz — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497000.0 €

Traditionally, natural products are classified into "natural product families". Within a family all congeners display specific structure elements, owing to their common biosynthetic pathway. This suggests a bio-inspired or "collective synthesis", as has been devised by D: W. MacMillan. However, a biosynthetic pathway is confined to these structure elements, thus limiting synthesis with regard to structure diversification. In this research proposal the applicant exemplarily devises a strategic concept to overcome these limitations, by replacing the dogma of "retrosynthetic analysis" with "structure pattern recognition". This concept is termed "Artificial Natural Product Systems Synthesis — ANaPSyS", and aims to supersede the current "logic of chemical synthesis" as a standard practice in this field. ANaPSyS exclusively categorizes natural products based on structural relationships — regardless of biogenetic origin. The structure pattern analysis groups natural products according to their shared core structure, and thereof creates a common precursor called "privileged intermediate (PI)". This intermediate is resembled in each of these natural products and is architecturally less complex. As a result every member of this natural product group can originate from a different natural product family and is obtained via this "privileged intermediate", which serves as basis for the artificial synthetic network. With ANaPSyS a synthetic route is not restricted to a single target structure anymore (as in conventional synthesis). In comparison with bio-inspired synthesis, which is limited to a single natural product family, ANaPSyS enables the synthesis of a whole set of natural product families. With every synthesis accomplished, the network is upgraded — hence diversification leads to a rise in revenue. As a consequence, synthetic efficiency is drastically enhanced, therefore profoundly boosting and facilitating lead structure development.

Mots-clés : natural product synthesis,total synthesis
Projet ERC : SafeSecS (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Saarland University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2445125.0 €

Trains, planes, and other safety- and security-critical systems that our society relies on are controlled by computer systems, as is much of our critical infrastructure, including the power grid and cellular networks. But can we trust in the safety and security of these systems? The starting point of SafeSecS is the observation that today’s hardware-software abstractions, instruction set architectures (ISAs), are fundamentally inadequate for the development of safe or secure systems. Indeed, ISAs abstract from timing, making it impossible to develop safety-critical systems that have to satisfy real-time constraints on top of them. Neither do ISAs provide sufficient security guarantees, making it impossible to develop secure systems on top of them. As a consequence, engineers are forced to rely on brittle timing and security models that are proven wrong time and again, as evidenced e.g. by the recent Spectre attacks; putting our society at risk. SafeSecS will attack the problem at its root by introducing a framework centered around hardware-software contracts that extend the guarantees provided by ISAs to capture key non-functional properties. Hardware-software contracts formally capture the expectations on correct hardware implementations and they lay the foundation for achieving safety and security guarantees as the software level. Below the hardware-software interface, SafeSecS will contribute modular design principles and tools to construct microarchitectures that provably satisfy a given hardware-software contract. Above the hardware-software interface, SafeSecS will develop rigorous, precise, and scalable techniques to guarantee key safety and security properties at the software level on top of hardware-software contracts. As a whole, SafeSecS will enable the systematic engineering of safe and secure hardware-software systems we can trust in.

Mots-clés : hardware software systems,real time systems
Projet ERC : TransMID (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Antwerp — Pays : Belgique — Rôle : Partner
Acronyme de l'entité : UAntwerp
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 435683.0 €

TransMID focuses on the development of novel methods to estimate key epidemiological parameters from both serological and social contact data, with the aim to significantly expand the range of public health questions that can be adequately addressed using such data. Using new statistical and mathematical theory and newly collected as well as readily available serological and social contact data (mainly from Europe), fundamental mathematical and epidemiological challenges as outlined in the following work packages will be addressed: (a) frequency and density dependent mass action relating potential effective contacts to transmission dynamics in (sub)populations of different sizes with an empirical assessment using readily available contact data, (b) behavioural and temporal variations in contact patterns and their impact on the dynamics of infectious diseases, (c) close contact household networks and the assumption of homogeneous mixing within households, (d) estimating parameters from multivariate and serial cross-sectional serological data taking temporal effects and heterogeneity in acquisition into account in combination with the use of social contact data, and (e) finally the design of sero- and social contact surveys with specific focus on serial cross-sectional surveys. TransMID is transdisciplinary in nature with applications on diseases of major public health interest, such as pertussis, cytomegalovirus and measles. Translational methodology is placed at the heart of TransMID resulting in the development of a unifying methodology for other diseases and settings. The development of a toolbox and accompanying software allow easy and effective application of these fundamentally improved techniques on many infectious diseases and in different geographic contexts, which should maximize TransMID’s impact on public health in Europe and beyond.

Mots-clés : infectious disease epidemiology,vaccination,outbreak risk
Projet ERC : TransPhorm (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Keele University — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 749289.45 €

TransPhorm will pioneer a transformative technology platform based on Nitrogen Vacancy (NV) magnetometry to enable the structure and function of transmembrane proteins (TMPs) to be studied in their native state with unprecedented sensitivity and resolution. TMPs reside in the membrane of biological cells and are critical to cellular function and communication. It is essential that TMPs are characterised in their native state as their structure and function is dependent on their interaction with the local environment. This is technically demanding and despite previous attempts using a multitude of complementary techniques no single method has provided a suitable solution. Here a breakthrough approach will be taken to demonstrate in situ TMP characterisation with single molecule sensitivity, nanoscale spatial resolution and millisecond measurement speed. The concepts proposed in TransPhorm are distinct from current implementations of NV magnetometry for detection and mapping of weak magnetic fields originating from external nuclear spins. Here magnetic field mapping will be achieved using a totally new approach based on widefield, high speed structured illumination total internal reflection microscopy. The concepts TransPhorm are built on will also enable structural and functional single molecular characterisation with high specificity by exploiting the outstanding sensitivity to the local environment of fluorine-19 Nuclear Magnetic Resonance (NMR) reporters and the ion selectivity of sodium-23 and potassium-39 NMR spectroscopy. In short, TransPhorm will deliver a ground-breaking technology to far surpass current state-of-the-art techniques and provide the extreme sensitivity needed to understand the molecular scale dynamic changes that underpin TMP function. Overall the strategy and technologies proposed here will pave an untravelled path to the realisation of nanoscale NMR imaging and deliver tremendous scientific gains.
Projet ERC : TransPhorm (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : University of Nottingham — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1685360.55 €

TransPhorm will pioneer a transformative technology platform based on Nitrogen Vacancy (NV) magnetometry to enable the structure and function of transmembrane proteins (TMPs) to be studied in their native state with unprecedented sensitivity and resolution. TMPs reside in the membrane of biological cells and are critical to cellular function and communication. It is essential that TMPs are characterised in their native state as their structure and function is dependent on their interaction with the local environment. This is technically demanding and despite previous attempts using a multitude of complementary techniques no single method has provided a suitable solution. Here a breakthrough approach will be taken to demonstrate in situ TMP characterisation with single molecule sensitivity, nanoscale spatial resolution and millisecond measurement speed. The concepts proposed in TransPhorm are distinct from current implementations of NV magnetometry for detection and mapping of weak magnetic fields originating from external nuclear spins. Here magnetic field mapping will be achieved using a totally new approach based on widefield, high speed structured illumination total internal reflection microscopy. The concepts TransPhorm are built on will also enable structural and functional single molecular characterisation with high specificity by exploiting the outstanding sensitivity to the local environment of fluorine-19 Nuclear Magnetic Resonance (NMR) reporters and the ion selectivity of sodium-23 and potassium-39 NMR spectroscopy. In short, TransPhorm will deliver a ground-breaking technology to far surpass current state-of-the-art techniques and provide the extreme sensitivity needed to understand the molecular scale dynamic changes that underpin TMP function. Overall the strategy and technologies proposed here will pave an untravelled path to the realisation of nanoscale NMR imaging and deliver tremendous scientific gains.
Projet ERC : OSIRIS (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Bern — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498275.0 €

Transducing information to and from biological environments is essential for bioresearch, neuroscience and healthcare. There has been recent focus on using organic semiconductors to interface the living world, since their structural similarity to bio-macromolecules strongly favours their biological integration. Either water-soluble conjugated polyelectrolytes are dissolved in the biological medium, or solid-state organic thin films are incorporated into bioelectronic devices. Proof-of-concept of versatile applications has been demonstrated – sensing, neural stimulation, transduction of brain activity, and photo-stimulation of cells. However, progress in the organic biosensing and bioelectronics field is limited by poor understanding of the underlying fundamental working principles. Given the complexity of the disordered, hybrid solid-liquid systems of interest, gaining mechanistic knowledge presents a considerable scientific challenge. The objective of OSIRIS is to overcome this challenge with a high-end spectroscopic approach, at present essentially missing from the field. We will address: 1) The nature of the interface at molecular and macroscopic level (assembly of polyelectrolytes with bio-molecules, interfacial properties of immersed organic thin films). 2) How the optoelectronics of organic semiconductors are affected upon exposure to aqueous environments containing electrolytes, biomolecules and cells. 3) How information is transduced across the interface (optical signals, thermal effects, charge transfer, electric fields, interplay of electronic/ionic transport). Via spectroscopy, we will target relevant optoelectronic processes with ultrafast time-resolution, structurally characterize the solid-liquid interface using non-linear sum-frequency generation, exploit Stark shifts related to interfacial fields, determine nanoscale charge mobility using terahertz spectroscopy in attenuated total reflection geometry, and simultaneously measure ionic transport.

Mots-clés : organic bioelectronics and biosensors,conjugated polymers and polyelectrolytes,organic thin films,solid liquid interfaces,ultrafast spectroscopy,terahertz time domain spectroscopy
Projet ERC : SelectiveTGFb-inhib (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Uppsala University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Transforming growth factor-b (TGFb) is a multifunctional cytokine which has important functions during embryonal development and in tissue homeostasis. In cancer, TGFb is often overexpressed and has both tumor suppressor effects (induction of growth arrest and apoptosis) and tumor promoting effects (stimulation of epithelial-mesenchymal transition (EMT) of tumor cells, stimulation of angiogenesis and cancer associated fibroblasts, and suppression of immune surveillance). Our aim is to elucidate the mechanisms for the pro-tumorigenic effects of TGFb and to develop selective inhibitors which can be used to suppress tumor invasiveness and metastasis in animal models, and later on for treatment of patients with advanced cancer. We think it is important to develop selective inhibitors, which do not affect the tumor suppressive effects of TGFb, since complete inhibition of TGFb may cause severe side effects and may even promote tumorigenesis. We plan to: 1. perform a systematic analysis of posttranslational modifications and interactors of the TGFb receptor I (TbRI) and II (TbRII), and determine their functional importance for the induction of various pro-tumorigenic pathways; 2. determine the mechanism whereby TGFb activates the tyrosine kinase Src, and its role in invasiveness and metastasis; 3. attempt to selectively inhibit the activation of phosphatidylinositol 3´-kinase by TGFb, in order to inhibit tumor cell survival and migration; 4. elucidate the functional role in the nucleus of the cleaved intracellular domain of TbRI, and attempt to inhibit its formation and thereby tumor metastasis; 5. determine the cellular compartment where the pro-tumorigenic signaling pathways are activated; 6. elucidate mechanisms for TGFb-induced EMT and develop candidate low molecular weight inhibitors that we have obtained from a screen, aiming at using them in vivo to suppress metastasis; 7. develop biomarkers to identity patient cohorts for treatment with selective TGFb inhibitors.
Projet ERC : MITICAT (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Ruhr University Bochum — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : RUB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498905.0 €

Transition metal based nanoparticles (NPs) are envisioned as viable alternatives to the scarce precious metal based catalysts used today for renewable energy conversion. Yet, probing their intrinsic activity to establish property-activity relations and so to smartly design superior catalysts, is impeded by two limitations of existing electrocatalytic techniques. First, the integral assessment of ensembles of non-identical NPs prohibits the identification of intrinsic activity differences. Second, the unknown effects of additives required analyzing the activity of often poorly conductive transition metal oxides, e.g. during the oxygen evolution reaction (OER), prohibit the access to quantitative data and comparable benchmarks. Very recently, we have proposed single NP electrochemistry to overcome both limitations. We demonstrated that the electrocatalytic OER response of individual CoFe2O4 NPs can be assessed in the absence of additives. However, we have not been able to extract property-activity relations, as NP characterization was limited to ex situ data. The groundbreaking strategy of this work is to combine intrinsic activity and physical property measurements of individual NPs. Physical characterization will comprise different online and ex situ methods to gain comprehensive property information. Numerical simulations will allow us to extract quantitative kinetic data from the electrochemical studies, allowing us to provide quantitative benchmarks of intrinsic catalyst performance. Cycling of NPs in a microfluidic platform will enable degradation studies and systematic modification “on the fly”. Moving towards application conditions, catalyst-support interactions will be studied by stepwise immobilization of catalysts on substrates. As a result of revealing intrinsic property-activity relations in electrocatalysis and of elucidating catalyst-support interactions, we will gain the understanding urgently needed to disruptively change electrocatalyst devolopment.

Mots-clés : single entity electrochemistry,nono particle characterization,microfluidics