ERC FUNDED PROJECTS

Alzheimer's disease (AD) is one of the most serious diseases mankind is now facing as its social and economical impacts are increasing fastly. AD is very complex and the amyloid-β (Aβ) peptide as well as metallic ions (mainly copper and zinc) have been linked to its aetiology. While the deleterious impact of Cu is widely acknowledged, intervention of Zn is certain but still needs to be figured out. The main objective of the present proposal, which is strongly anchored in the bio-inorganic chemistry field at interface with spectroscopy and biochemistry, is to design, synthesize and study new drug candidates (ligands L) capable of (i) targeting Cu(II) bound to Aβ within the synaptic cleft, where Zn is co-localized and ultimately to develop Zn-driven Cu(II) removal from Aβ and (ii) disrupting the aberrant Cu(II)-Aβ interactions involved in ROS production and Aβ aggregation, two deleterious events in AD. The drug candidates will thus have high Cu(II) over Zn selectively to preserve the crucial physiological role of Zn in the neurotransmission process. Zn is always underestimated (if not completely neglected) in current therapeutic approaches targeting Cu(II) despite the known interference of Zn with Cu(II) binding. To reach this objective, it is absolutely necessary to first understand the metal ions trafficking issues in presence of Aβ alone at a molecular level (i.e. without the drug candidates).This includes: (i) determination of Zn binding site to Aβ, impact on Aβ aggregation and cell toxicity, (ii) determination of the mutual influence of Zn and Cu to their coordination to Aβ, impact on Aβ aggregation, ROS production and cell toxicity. Methods used will span from organic synthesis to studies of neuronal model cells, with a major contribution of a wide panel of spectroscopic techniques including NMR, EPR, mass spectrometry, fluorescence, UV-Vis, circular-dichroism, X-ray absorption spectroscopy...

1 499 948 €

Start date: 2015-03-01, End date: 2020-02-29

Developing brain implants is crucial to better decipher the neuronal information and intervene in a very thin way on neural networks using microstimulations. This project aims to address two major challenges: to achieve the realization of a highly mechanically stable implant, allowing long term connection between neurons and microelectrodes and to provide neural implants with a high temporal and spatial resolution. To do so, the present project will develop implants with structural and mechanical properties that resemble those of the natural brain environment. According to the literature, using electrodes and electric leads with a size of a few microns allows for a better neural tissue reconstruction around the implant. Also, the mechanical mismatch between the usually stiff implant material and the soft brain tissue affects the adhesion between tissue cells and electrodes. With the objective to implant a highly flexible free-floating microelectrode array in the brain tissue, we will develop a new method using micro-nanotechnology steps as well as a combination of polymers. Moreover, the literature and preliminary studies indicate that some surface chemistries and nanotopographies can promote neurite outgrowth while limiting glial cell proliferation. Implants will be nanostructured so as to help the neural tissue growth and to be provided with a highly adhesive property, which will ensure its stable contact with the brain neural tissue over time. Implants with different microelectrode configurations and number will be tested in vitro and in vivo for their biocompatibility and their ability to record and stimulate neurons with high stability. This project will produce high-performance generic implants that can be used for various fundamental studies and applications, including neural prostheses and brain machine interfaces.

1 499 850 €

Start date: 2015-08-01, End date: 2021-07-31

Animals display a tremendous diversity of patterns ‒from the colourful designs that adorn their body to repeated segmented appendages. Natural patterns result from the formation of discrete domains within developing tissues through the integration of positional cues by cells that consequently adopt specific fates and produce spatial heterogeneity. How can such developmental processes underlie the apparent complexity and diversity of natural patterns? We propose to address this long-standing question with an innovative experimental design: we will make use of natural variation as a powerful tool to facilitate the identification of patterning molecules and morphogenetic events. We will study colour pattern, a crucial adaptive trait that varies extensively in nature, from large colour domains to periodic designs. In amniotes, colour pattern is formed by spatial differences in the distribution of pigment cells and integumentary appendages. While the pigmentation system has been well characterized, the mechanisms governing the formation of compartments in the skin of wild animals have remained unclear, largely because laboratory models do not display ecologically-relevant colour patterns. We will use a combination of forward genetics, developmental biology, modelling, and imaging to study natural variation in the large colour domains of Estrildid finches and the periodic stripes of Galliform birds. For both phenotypes, we will characterize the organization of the embryonic skin and the mode of patterning (i.e., instructional patterning via external cues vs locally-occurring self-organization) underlying their formation, and identify the molecular factors and developmental processes contributing to their variation. Results from these studies will elucidate the biochemical events and tissue rearrangements orchestrating colour patterning in development and shed light on how these processes shape natural variation in this trait‒ and more generally, in natural patterns.

1 483 144 €

Start date: 2015-05-01, End date: 2020-04-30

For the last 15 years, optics has undergone a remarkable evolution towards ever decreasing sizes, better integration in complex systems, and more compact devices readily available to mass markets. Whereas traditional optics is at the centimeter scale, newly developed techniques use nanoscale objects to control, guide, and focus light. From the capability to shape metallic and dielectric nanostructures has emerged the field of nanophotonics. Advances in nanophotonics offer the possibility to control the material’s optical properties to create artificial materials with electromagnetic properties not found in nature. Man-made 3D metamaterials have interesting fundamental aspects and present many advantages with respect to conventional devices. Unexpected effects have led to the development of interesting applications like high resolution lenses and cloaking devices. Inspired by this new technology, we have developed new 2D metamaterials. Our flat metamaterials (metasurfaces) are much simpler to manufacture than their 3D counterparts. By depositing a set of nanostructures at an interface, we can immediately control the light properties; unlike refractive optical components, the wavefront is modified without propagation. As of today, these interfaces are created using metallic nanostructures and work in the infrared. In this ERC, we plan to extend the concept of optical metasurfaces in the visible which is the most important wavelength range for applications. By combining with optically active semiconductors such as InGaAlN, we will add optical gain and modulation capability to the system to create new, efficient optoelectronic devices. The response of the metasurfaces is tunable by changing the environment surrounding the nanostructures. We will use this property to create ultrathin reconfigurable flat devices. Metasurfaces will be integrated with AlN/GaN to modulate light at high frequencies and further exploited to control polariton gases in solid state metasystems.

2 000 000 €

Start date: 2015-09-01, End date: 2020-10-31

Detecting and imaging magnetic fields with high sensitivity and nanoscale resolution is a topic of crucial importance for a wealth of research domains, from material science, to mesoscopic physics, and life sciences. This is obviously also a key requirement for fundamental studies in nanomagnetism and the design of innovative magnetic materials with tailored properties for applications in spintronics. Although a remarkable number of magnetic microscopy techniques have been developed over the last decades, imaging magnetism at the nanoscale remains a challenging task. It was recently realized that the experimental methods allowing for the detection of single spins in the solid-state, which were initially developed for quantum information science, open new avenues for high sensitivity magnetometry. In that spirit, it was recently proposed to use the electronic spin of a single nitrogen-vacancy (NV) defect in diamond as a nanoscale quantum sensor for scanning probe magnetometry. This approach promises significant advances in magnetic imaging since it provides quantitative and vectorial magnetic field measurements, with an unprecedented combination of spatial resolution and magnetic sensitivity, even under ambient conditions. The IMAGINE project intend to exploit the unique performances of scanning-NV magnetometry to achieve major breakthroughs in nanomagnetism. We will first explore the structure of domain walls and individual skyrmions in ultrathin magnetic wires, which both promise disruptive applications in spintronics. This will lead (i) to solve an important academic debate regarding the inner structure of domain walls and (ii) to the first detection of individual skyrmions in ultrathin magnetic wire under ambient conditions. This might result in a new paradigm for spin-based applications in nanoelectronics. We will then explore orbital magnetism in graphene, which has never been observed experimentally and is the purpose of surprising theoretical predictions.

1 498 810 €

Start date: 2015-09-01, End date: 2020-08-31

Spectroscopy is a powerful tool to probe matter. By measuring the spectrum of elementary excitations, one reveals the symmetries and interactions inherent in a physical system. Mesoscopic devices, which preserve quantum coherence over lengths larger than the atomic scale, offer a unique possibility to both engineer and investigate excitations at the single quanta level. Unfortunately, conventional spectroscopy techniques are inadequate for coupling radiation to mesoscopic systems and detecting their small absorption signals. I propose an on-chip, Josephson-junction based spectrometer which surpasses state-of-the-art instruments and is ideally suited for probing elementary excitations in mesoscopic systems. It has an original design providing uniform wideband coupling from 2-2000 GHz, low background noise, high sensitivity, and narrow linewidth. I describe the operating principle and design of the spectrometer, show preliminary results demonstrating proof-of-concept, and outline three experiments which exploit the spectrometer to address important issues in condensed matter physics. The experiments are: measuring the lifetime of single quasiparticle and excited Cooper pair states in superconductors, a topic relevant for quantum information processing; determining whether graphene has a bandgap, a fundamental yet unresolved question; and recording a clear spectroscopic signature of Majorana bound states in topological superconductor weak links. Various applications of the superconducting circuits developed for the spectrometer include a Josephson vector network analyzer, a cryogenic mixer, a THz camera, a detector for radioastronomy, and a scanning microwave impedance microscope. In itself the proposed JJ spectrometer is a general purpose tool that will benefit researchers studying mesoscopic systems. Ultimately, Josephson junction spectroscopy should not only be useful to detect existing elementary excitations but also to discover new ones.

1 997 498 €

Start date: 2015-04-01, End date: 2020-03-31

Plant development is continuous throughout their lifetime and reflects their ability to adapt to their environment. This developmental plasticity is very obvious in the development of the root system. Surprisingly, the fundamental mechanisms of root development have been studied into great detail but the effect of the environment on its plasticity is still largely unknown. I will use phosphate, since this nutrient has a very low mobility in soil, as a mean to study plant developmental adaptation in white lupin. This species has developed extreme adaptive mechanism to improve phosphate uptake by producing structures called “cluster roots”. They are dense clusters of lateral roots with determinate development and highly specific physiology. I will develop new tools to identify cluster root mutants in white lupin, sequence white lupin genome, perform tissues specific transcriptomics and perform full molecular characterization of selected genes. This project will also lead me to compare adaptive mechanisms between white lupin and narrow-leafed lupin, a closely related species that does not produce cluster roots. We will also test whether it is possible to transfer the ability to form cluster roots in this species. Altogether, this project will lead to a major advance in our capacity to understand how plants are able to sense and respond to their environment and how evolution has selected adaptive developmental mechanisms to improve their capacity to use limited resources. This project focuses on the most extreme developmental adaptation produced in response to phosphate starvation. It is ambitious, as it will necessitate the development of several tools. However, it is highly feasible since it builds on my previous experience and important outcome can be expected in term of crop improvement and means to reduce the use of phosphate fertilizers.

1 997 103 €

Start date: 2015-09-01, End date: 2020-08-31

According to biologists, there is a need for quantitative models that are able to cope with the complexity of problems arising in the field of life sciences. Here, complexity refers to the interplay between various scales that are not clearly separate. The great challenge of the MESOPROBIO project is to analyse complex PDE models for biological propagation phenomena at the mesoscale. By analogy with the kinetic theory of gases, this is an intermediate level of description between the microscale (individual-based models) and the macroscale (parabolic reaction-transport-diffusion equations). The specific feature common to all the models involved in the project is the local heterogeneity with respect to a structure variable (velocity, phenotypical trait, age) which requires new mathematical methods. I propose to push analysis beyond classical upscaling arguments and to track the local heterogeneity all along the analysis. The biological applications are: concentration waves of bacteria, evolutionary aspects of structured populations (with respect to dispersal ability or life-history traits), and anomalous diffusion. The mathematical challenges are: multiscale analysis of PDE having different properties in different directions of the phase space, including nonlocal terms (scattering, competition), and possibly lacking basic features of reaction-diffusion equations such as the maximum principle. The outcomes are: travelling waves, accelerating fronts, approximation of geometric optics, nonlocal Hamilton-Jacobi equations, optimal foraging strategies and evolutionary dynamics of phenotypical traits. Emphasis will be placed on quantitative results with strong feedback towards biology. The project will be conducted in Lyon, a French hub for mathematical biology and hyperbolic equations. There will be close interaction with biologists in order to establish the most appropriate questions to answer. Several collaborations in Europe (UK, Austria) will be developed.

1 091 688 €

Start date: 2015-09-01, End date: 2020-08-31

New models of fluid transport are expected to emerge from the confinement of liquids at the nanoscale, where the behaviour of matter strongly departs from common expectations. This is the field of the Nanofluidics: taking inspiration from the solution found by evolved biological systems, new functionalities will emerge from the nanometre scale, with potential applications in ultrafiltration, desalination and energy conversion. Nevertheless, advancing our fundamental understanding of fluid transport on the smallest scales requires mass and ion dynamics to be ultimately characterized across channels with dimensions close to the molecular size. A major challenge for nanofluidics thus lies in building distinct and well-controlled nanochannels, amenable to the systematic exploration of their properties. This project will tackle several complementary challenges. On the first hand the realization of new kind of fluidic devices allowing the study of fluid and ion transport at the nanoscale: these new experimental devices will be obtained by using nanostructures like building blocks as already shown by realising a fluidics set-up based on transmembrane nanotubes; in parallel a dedicated plateform for the characterization of fluid transport will be developed based on electrokinetics and optical detection set-ups. On the other hand, profiting of such experimental set-ups, I will look for the limit of the classical description of the fluid dynamics, focusing on new functionalities emerging from exotic behaviour of fluids at the nanometer level. This will be done by studying different kind of nanofluidics set-up such as carbon and boron-nitride nanotube, ultrathin pierced graphene and h-BN sheet and composite materials. I aim the creation of a link between fundamental research on soft matter and nanoscience-condensed matter with a an attention on the energy production domain, assuring a fruitful transfer between the fundamental findings and new industrial applications.

1 494 000 €

Start date: 2015-04-01, End date: 2020-03-31

Ambitious Questions: * How does the relatively calm macroscopic universe survive and emerge from the violent quantum fluctuations of its underlying microphysics? * How do classical notions of space and time emerge from fundamental principles, and what governs their evolution? These questions are difficult to answer---perhaps impossible given current ideas and frameworks---but I believe a strategic path forward is to thoroughly understand the quantum predictions of our Yang-Mills and Gravity theories, and unambiguously identify their non-perturbative UV completions. The first step forward, and the goal of this project, is to move towards the trivialization of perturbative calculations. Consider the notion of failure-point calculations -- calculations that push modern methods and world-class technologies to their breaking-point. Such calculations, for their very success, engender the chance of cultivating and exploiting previously unappreciated structure. In doing so, such calculations advance the state of the art forward to some degree, dependent on the class of the problems and nature of the solution. With scattering amplitude calculations, we battle against (naive) combinatorial complexity as we go either higher in order of quantum correction ( loop order ), or higher in number of external particles scattering (multiplicity), so our advances must be revolutionary to lift us forward. Yet I and others have shown that the very complications of generalized gauge freedom promise a potential salvation at least as powerful as the complications that confront us. The potential reward is enormous, a rewriting of perturbative quantum field theory to make these principles manifest and calculation natural, an ambitious but now realistic goal. The path forward is optimized through strategic calculations.

1 299 958 €

Start date: 2015-06-01, End date: 2020-05-31

"The objectives of this proposal, PRISTINE (high PRecision ISotopic measurements of heavy elements in extra-Terrestrial materials: origIN and age of the solar system volatile Element depletion), are to develop new cutting edge high precision isotopic measurements to understand the origin of the Earth, Moon and solar system volatile elements and link their relative depletion in the different planets to their formation mechanism. In addition, the understanding of the origin of the volatile elements will have direct consequences for the understanding of the origin of the Earth’s water. To that end, we will approach the problem from two angles: 1) Develop and use novel stable isotope systems for volatile elements (e.g. Zn, Ga, Cu, and Rb) in terrestrial, lunar and meteoritic materials to constrain the origin of solar system’s volatile element depletion 2) Determine the age of the volatile element depletion by using a novel and original approach: calculate the original Rb/Sr ratio of the Solar Nebula by measuring the isotopic composition of the Sun with respect to Sr via the isotopic composition of solar wind implanted in lunar soil grains. The stable isotope composition (goal #1) will give us new constraints on the mechanisms (e.g. evaporation following a giant impact or incomplete condensation) that have shaped the abundances of the volatile elements in terrestrial planets, while the timing (goal #2) will be used to differentiate between nebular events (early) from planetary events (late). These new results will have major implications on our understanding of the origin of the Earth and of the Moon, and they will be used to test the giant impact hypothesis of the Moon and the origin of the Earth’s water."

1 487 500 €

Start date: 2015-04-01, End date: 2020-03-31

"The ability of cells to use the actin cytoskeleton for a diversity of cellular processes is due to the fact that actin filaments, although assembled from identical subunits, are organized in a wide variety of structures of appropriate geometrical, dynamical and rheological properties. Key players in this regulation are specific sets of actin binding proteins (ABPs) interacting with each actin networks, to modulate spatially and temporally their properties. With this project, I want to understand 1/ how cells can generate the formation of actin structures of appropriate ABP composition from a common pool of cytoplasmic components and 2/ the relationship between the ABP composition of an actin network, its geometrical and dynamical properties, and its response to mechanical deformations. I will hypothesize that the generation of an actin network of appropriate ABP composition can be explained with an original model, taking into account the facts that 1/ actin filaments in cells are not all structurally identical, but adopt specific conformations that are favored and stabilized by certain families of ABPs; and 2/ the interaction of ABPs with actin depends of the geometrical organization of the filaments. Because this project imposes to study protein-protein interactions in the presence of multiple partners, I propose to develop an unprecedented strategy combining 1/ "bottom-up" reconstitutions, where limited sets of ABPs are added one-by-one in the system to understand their combined activities with actin; and 2/ "top-down" reconstitutions with protein extracts prepared from a genetically-tractable organism (the yeast S. cerevisiae), where proteins can be removed one-by-one, in order to study actin network properties in near-physiological conditions. This project will shed a new light on how cells organize their interior, and will represent a unique opportunity to understand how modifications in the expression of ABPs are associated with actin network defects."

1 500 000 €

Start date: 2015-09-01, End date: 2020-08-31

Complex Stein spaces may be thought of as analytic analogues of the affine schemes of algebraic geometry. They may be characterized in several manners: using convergence of holomorphic functions, topological properties or potential-theoretic properties, for instance. Especially useful for applications is the fact that their coherent cohomology vanishes. Despite the crucial importance of this theory in complex analytic geometry, its p-adic counterpart has hardly been sketched. In the setting of Berkovich geometry (one among the several notions of p-adic geometry), recent developments have enabled to get a fine understanding of the topology of the spaces (work of Berkovich and Hrushovski-Loeser) and to define the basic tools of potential theory (work of Baker-Rumely, Thuillier, Boucksom-Favre-Jonsson and Chambert-Loir-Ducros). The conditions for a comprehensive study of p-adic Stein spaces are now met; this will be our first goal. The theory will then be used to investigate envelopes of holomorphy and meromorphy. As an application, I plan to derive rationality criteria for power series over function fields. The second part of the project is devoted to the theory of Stein spaces for Berkovich spaces over rings of integers of number fields (where all the places appear on an equal footing). Those spaces have hardly been studied and only a very small part of the usual analytic machinery is available in this setting. Here, my main goal will consist in proving the basic and fundamental fact that relative polydisks are Stein spaces (in the cohomological sense). This will allow a deeper investigation of rings of convergent arithmetic power series (i.e. with integral coefficients) and will lead up to properties related to commutative algebra but also to the inverse Galois problem. Knowing that the coherent cohomology of polydisks vanishes also opens the road towards computing global cohomology groups for projective analytic spaces over ring of integers of number fields.

1 153 750 €

Start date: 2015-07-01, End date: 2020-06-30