Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MapItAll (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of Manchester — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1444378.71 €

My proposal is to map out the 3D structure of the Universe over an unprecedentedly broad swath of cosmic time, covering 13 billion years of cosmic history. I will do this by using radio telescopes to detect the 21cm emission from neutral hydrogen. The detailed statistical properties of the maps will allow us to answer some of the most pressing questions in cosmology, such as how fast space is expanding, what the physical properties of dark energy are, and how the first stars and galaxies lit up the Universe. All experiments currently trying to make these observations are severely limited by systematic effects, exacerbated by the extremely high dynamic range between the cosmological signal and many other sources of radio emission. Even tiny calibration errors can cause huge artefacts in the data that make it extremely difficult to pick out the target signal. While a great deal of work has gone into designing methods to analyse the data, they are not yet accurate enough – by a factor of 100 by some measures. I will develop a statistical analysis framework called “Total Calibration” that can deliver the remaining two orders of magnitude of improvement, and apply it to the most sensitive data available. The result will be precise, systematics-free maps and the most robust statistical measurements of large-scale structure ever made in the radio. Total Calibration seeks to model all of the relevant degrees of freedom in the data simultaneously, in one large global model of the signal, contaminants, and the calibration of the telescope. This is highly complex, and has never been done before. By applying total calibration to sensitive but complex data from two cutting-edge telescopes, HERA and MeerKAT, I will obtain the most robust constraints on the 21cm signal to date, from redshifts 0–1.4 (late times) and 5–27 (reionisation/Cosmic Dawn), to constrain the physical processes that shaped the cosmic energy budget at high redshift and any possible evolution of dark energy.

Mots-clés : reionization,intensity mapping,neutral hydrogen,astrostatistics,observational cosmology
Projet ERC : INTESTINANOS (Horizon 2020, appel 2014, Starting 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 : 1706250.0 €

My research program explores molecular interplay between drug, dosage form and the complex environment of the gastrointestinal tract (GIT). Drug molecules currently being discovered to cure e.g. CNS diseases, cancer and the metabolic syndrome show poor water solubility and 70-90% of recently discovered drugs have too poor solubility to allow absorption from the GIT. For such compounds the dosage form can significantly improve the absorption. My long-term goal is to establish a computational platform that predicts, from molecular structures and computational tools, the development potential of drug molecules to well-functioning orally administered medicines. A major gap to understand drug performance in the intestine is the poor knowledge of the dynamics of solubilizing lipoidal nanostructures (micelles, vesicles, oil droplets) present in the fluid. This project explores restructuring of these lipid colloids in response to intake of food or dosage forms, enzymatic digestion, absorption and transit along the GIT. Novel experimental tools are developed to reveal the impact of these nanostructures on drug solubilization, supersaturation and likelihood of precipitation in vivo, all being important for drug absorption. The experimental results are fed into in silico models taking use of Molecular Dynamics simulations to develop a computational platform predicting drug performance in the dynamic intestinal milieu. The novel tools designed herein will allow dosage forms that improve performance and increase drug absorption after oral administration to, for the first time, be designed by computational means. The results of this project, in particular the novel in silico tools exploring rearrangement of lipoidal nanostructures, are highly important to related areas such as GIT disease models and food processing but also have wider applications in e.g. studies of intracellular vesicle rearrangements and transport processes in plants.

Mots-clés : poorly soluble drugs,dissolution,intestinal fluid,lipolysis,colloidal rearrangement,lipid based drug delivery,molecular dynamics simulations,computational pharmaceutics
Projet ERC : ECOEVODRTB (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Swiss Tropical and Public Health Institute — Pays : Suisse — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1926625.0 €

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), is the main cause of human deaths due to infection in general, and to antimicrobial resistance in particular. Little is known on the within-host evolution of Mtb. Theory predicts that in chronic infections like TB, short-sighted evolution operates in the light of a trade-off between virulence and transmission. This trade-off is particularly relevant in the context of drug resistance, given the fitness costs of resistance. However, the role of short-sighted evolution in TB has never been explored empirically. Theory and model systems further predict that phenotypic drug tolerance facilitates the emergence of drug resistance, but the relevance of phenotypic drug tolerance for drug resistance evolution in the clinic has not been established for TB or any other bacterial disease. To address these and related questions, I propose to build on my recent work on the transmission of drug-resistant Mtb with a new focus on the within-patient evolution of drug-resistant Mtb and its link to between-patient evolution during transmission. Specifically, I shall: 1) Define the genomic characteristics and evolutionary forces shaping multidrug-resistant Mtb populations in individual patients over time and across different body compartments; 2) Compare the genomic and phenotypic properties of multidrug-resistant Mtb populations in individual patients to those circulating within the corresponding patient population; 3) Determine the effect of suboptimal patient treatment and phenotypic drug tolerance on drug resistance evolution in Mtb inside patients. By combining population genomics of Mtb sampled sequentially and from surgical specimens with experimental evolution and phenotypic characterization of clinical and experimentally evolved strains, this project will generate new insights relevant to both basic science and global public health.

Mots-clés : ecology,evolution,fitness,tuberculosis,mycobacteria,genomics,epidemiology,antibiotics,resistance,tolerance,persistence
Projet ERC : MyelinPlasticity (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1999729.0 €

Myelin is essential for normal brain function, as it provides fast signal transmission, promotes synchronisation of neuronal signals and helps to maintain neuronal function. Alterations in myelination are increasingly being implicated as a mechanism for sensory-motor learning. The importance of myelin becomes evident in diseases, such as multiple sclerosis (MS), where myelin damage causes cognitive and motor disability. Moreover, recent studies have highlighted the contribution of myelin to many diseases that were previously considered to be ‘neuronal’, such as dementia, schizophrenia, autism and bipolar disorder. Despite the profound importance of myelin, there are serious deficits in our understanding of how myelination is regulated and to what extent myelin is plastic; which are impediments for understanding both the functional connectivity of the central nervous system (CNS) and white matter disease. We, and others, have shown that myelination can be regulated by neuronal activity, thus I hypothesize that neuronal activity is a driver of myelin plasticity, similar to synaptic plasticity. By using an innovative approach combining electrophysiology, optogenetics, pharmacogenetics, imaging, transgenic animals, behavioural tests, and in vitro and in vivo models of myelination, this research programme will determine mechanisms that mediate neuronal activity dependent myelination, establish to what extent myelin changes occur with learning and identify to what extent myelin is plastic. The outcome of this proposal will break new ground in our understanding of myelin plasticity, and has the potential to provide novel therapeutic strategies for myelin regeneration in white matter diseases such as MS.

Mots-clés : myelin,oligodendrocyte,glia,neuron glia interactions,neuronal activity,myelination,axon,myelin plasticity,neurotransmitter signalling
Projet ERC : M6AQuantKit (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

N6-Methyladenosine (m6A) plays fundamental roles in regulation of metabolism, stem cell self-renewal, and metastasis. Consistently its dysregulation is implicated in a variety of human cancers including leukemia, glioblastoma and hepatocellular carcinoma. Consequently, the potential of m6A both as a novel cancer diagnostic and as a drug target has raised immense interest in scientific community and industry. For unravelling m6A functions, for the development of therapeutics and for prioritizing diseases and disease states most likely to benefit from therapeutic targeting of the methylation complex, it is thus of crucial importance to be able to measure the levels at which m6A is present. In our ERC project we addressed this challenge and developed MAZTER-seq, a methodology for quantifying m6A levels relying on a methylation-sensitive ribonuclease (RNase), representing the first systematic approach for quantitative interrogating of m6A levels. The goal of the project is to advance our approach as commercializable kit for quantitative profiling of m6A. In the PoC, we will develop multiplexed protocol of MAZTER-seq that allows the simultaneous processing and interrogation of multiple samples from low amounts of sample material. The kit, coupled with streamlined data analysis tool, addresses a major market need and exhibits significant added value for academic labs and the biotech & pharma industries targeting the methylation machinery, e.g. for creating novel RNA based therapeutics. Our readout from low-input material makes m6A monitoring amenable to patient samples, representing an unmet challenge across all our target market. Thus, our goal is to create a startup which harnesses the vast market potential. In the PoC, the commercialization considerations are advanced through actions such as, seeking market feedback, strengthening the IP position, defining the business strategy and planning business execution.

Mots-clés : rna modification,regulation of gene expression,rna based therapeutics and diagnostics,commercialization
Projet ERC : NUCLEARWATERS (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : KTH Royal Institute of Technology — Pays : Suède — Rôle : PI
Acronyme de l'entité : KTH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1991008.0 €

NUCLEARWATERS develops a groundbreaking new approach to studying the history of nuclear energy. Rather than interpreting nuclear energy history as a history of nuclear physics and radiochemistry, it analyses it as a history of water. The project develops the argument that nuclear energy is in essence a hydraulic form of technology, and that it as such builds on centuries and even millennia of earlier hydraulic engineering efforts worldwide – and, culturally speaking, on earlier “hydraulic civilizations”, from ancient Egypt to the modern Netherlands. I investigate how historical water-manipulating technologies and wet and dry risk conceptions from a deeper past were carried on into the nuclear age. These risk conceptions brought with them a complex set of social and professional practices that displayed considerable inertia and were difficult to change – sometimes paving the way for disaster. Against this background I hypothesize that a water-centred nuclear energy history enables us to resolve a number of the key riddles in nuclear energy history and to grasp the deeper historical logic behind various nuclear disasters and accidents worldwide. The project is structured along six work packages that problematize the centrality – and dilemma – of water in nuclear energy history from different thematic and geographical angles. These include in-depth studies of the transnational nuclear-hydraulic engineering community, of the Soviet Union’s nuclear waters, of the Rhine Valley as a transnational and heavily nuclearized river basin, of Japan’s atomic coastscapes and of the ecologically and politically fragile Baltic Sea region. The ultimate ambition is to significantly revise nuclear energy history as we know it – with implications not only for the history of technology as an academic field (and its relationship with environmental history), but also for the public debate about nuclear energy’s future in Europe and beyond.

Mots-clés : nuclear energy,nuclear disasters,hydraulic engineering,water history,transnational history
Projet ERC : ULT-NEMS (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Université Grenoble Alpes — Pays : France — Rôle : Partner
Acronyme de l'entité : UGA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 24198.96 €

Nano-electro-mechanical devices (NEMS) are extremely small objects that can be actuated and detected by electric means. They are in the first place transducers that can be used as probes for forces down to the molecular level. Top-down fabricated NEMS using conventional microelectronics techniques are simple devices that intimately link mechanical and electrical degrees of freedom. As such, they can be viewed as model systems from basic (linear) harmonic motion up to complex nonlinear dynamics. The most intriguing experimental situation is attained when the devices are cold enough to behave according to the laws of quantum mechanics, instead of classical physics. This leads to a unique approach of the classical-to-quantum crossover with truly macroscopic position-states. Complementarily, at low temperatures the forces sensed by the NEMS arise from materials themselves cold enough to exhibit exotic quantum properties, originating either in the devices’ constitutive amorphous materials and their intrinsic elusive Tunneling Systems, or from their interaction with a sophisticated fluid like superfluid 3He. I propose unique research linking ultra-low temperature physics and nano-mechanics, building on my knowledge of both fields and my experience in superconducting quantum circuits. The research has two identified axes, which aim at pushing both the “sensor” and “model system” aspects of NEMS down to their quantum retrenchments. Macroscopic quantum position-states can be engineered with a hybrid quantum circuit arrangement (a combination of NEMS, microwaves and quantum bit), while topological states of confined superfluid 3He with their elementary excitations can be mechanically probed by dedicated NEMS (measuring friction). The scientific impact of this research is extremely wide, tackling fundamental questions like: what/where is the boundary between quantum and classical worlds, and do Majorana particles (potentially obtained in topological 3He) exist at all?

Mots-clés : low temperature physics,quantum fluids and solids,quantum mechanics and decoherence,non linear dynamics
Projet ERC : Dynasore (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Forschungszentrum Jülich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FZJ
Type d'entité : Recherche
Financement ERC de l'entité : 1994879.0 €

Nano-spin-orbitronics is an emerging and fast growing field that aims at combining three degrees of freedom − spin, charge and spin-orbit interaction − to explore new nanotechnologies stemming from fundamental physics. New magnetic phases of matter are investigated using, in particular, atomic design to tailor beneficial physical properties down to the atomic level. Storage, transport and manipulation of magnetic information within a small set of atoms does not only require a fundamental understanding of their ground-state properties from the perspective of quantum mechanics, but crucially also their dynamical excited states. We propose to go beyond the state of the art by investigating from first-principles the dynamical properties of chiral spin textures in nanostructures from 2-dimensions to 0-dimension with these nanostructures being deposited on different substrates where spin-orbit interaction plays a major role. Understanding their response to external dynamical fields (electric/magnetic) or currents will impact on the burgeoning field of nano-spin-orbitronics. Indeed, to achieve efficient manipulation of nano-sized functional spin textures, it is imperative to exploit and understand their resonant motion, analogous to the role of ferromagnetic resonance in spintronics. A magnetic skyrmion is an example of a spin-swirling texture characterized by a topological number that will be explored. This spin state has huge potential in nanotechnologies thanks to the low spin currents needed to manipulate it. Based on time-dependent density functional theory and many-body perturbation theory, our innovative scheme will deliver a paradigm shift with respect to existing theoretical methodologies and will provide a fundamental understanding of: (i) the occurrence of chiral spin textures in reduced dimensions, (ii) their dynamical spin-excitation spectra and the coupling of the different excitation degrees of freedom and (iii) their impact on the electronic structure.

Mots-clés : chiral low dimensional magnets,magnetic nanodevices,dynamical magnetic excitations,spin orbit interaction
Projet ERC : NAPOLI (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 500000.0 €

Nanoporous polymer membranes (NPMs) play a crucial, irreplaceable role in fundamental research and industrial usage, including separation, filtration, water treatment and sustainable environment. The vast majority of advances concentrate on neutral or weakly charged polymers, such as the ongoing interest on self-assembled block copolymer NPMs. There is an urgent need to process polyelectrolytes into NPMs that critically combine a high charge density with nanoporous morphology. Additionally, engineering structural asymmetry/gradient simultaneously in the membrane is equally beneficial, as it would improve membrane performance by building up compartmentalized functionalities. For example, a gradient in pore size forms high pressure resistance coupled with improved selectivity. Nevertheless, developing such highly charged, nanoporous and gradient membranes has remained a challenge, owing to the water solubility and ionic nature of conventional polyelectrolytes, poorly processable into nanoporous state via common routes. Recently, my group first reported an easy-to-perform production of nanoporous polyelectrolyte membranes. Building on this important but rather preliminary advance, I propose to develop the next generation of NPMs, nanoporous asymmetric poly(ionic liquid) membranes (NAPOLIs). The aim is to produce NAPOLIs bearing diverse gradients, understand the unique transport behavior, improve the membrane stability/sustainability/applicability, and finally apply them in the active fields of energy and environment. Both the currently established route and the newly proposed ones will be employed for the membrane fabrication. This proposal is inherently interdisciplinary, as it must combine polymer chemistry/engineering, physical chemistry, membrane/materials science, and nanoscience for its success. This research will fundamentally advance nanoporous membrane design for a wide scope of applications and reveal unique physical processes in an asymmetric context.

Mots-clés : porous membrane,polyelectrolyte,poly ionic liquid,asymmetric membrane
Projet ERC : NanoPaths (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
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 : 1498746.25 €

Nanotechnology applied to medicine has opened tremendous opportunities for the design of devices capable of targeting cancer and other diseases, and to deliver therapies selectively to locations where drugs currently can scarcely arrive. Translation of nanomedicines to the clinic however still remains challenging and the mechanistic details of the pathways used by cells to internalize and process man-made nanoparticles are still poorly understood. NanoPaths aims to understand how nanoparticles are processed by cells and in particular (1) to disentangle the mechanisms they use to enter cells, and (2) discover whether highly curved nanosized objects can assist cell membrane curvature, thus play an active role in their internalization; (3) to isolate the structures in which nanoparticles are internalized, in order to understand early sorting by cells, and further characterise the machinery for internalization; and finally (4) to define heterogeneity in cell response to nanoparticles in all of these aspects due to population context (i.e. cell cycle, local cell density) and identify eventual rare-cell behaviours. Several methods to ensure quantitative nanoparticle-cell interaction studies and discriminate cell subpopulations have already been developed in my previous work and now allow me to ask these questions. These methods will be combined with novel approaches applied for the first time in this arena, such as the use of full genome screens to study uptake; single molecule fluorescence methods to understand the role of nanoparticle curvature; novel cell fractionation methods coupled to quantitative proteomics to identify key proteins involved in uptake and early sorting; individual cell analysis to address heterogeneity in cell response to nanoparticles and study rare cells of interest. By disentangling the pathways involved in nanoparticle uptake and early sorting, the knowledge gained with NanoPaths will allow guiding the design of successful nanomedicines.

Mots-clés : nanoparticles,nanoparticle cell interactions,nanomedicine,nanosafety,nanoparticle uptake