ERC FUNDED PROJECTS

Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to: • Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations. • Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath. • Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots. In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.

2 498 086 €

Start date: 2018-09-01, End date: 2023-08-31

Vaccines and immunodiagnostics have been vital for public health and medicine, however a quantitative molecular understanding of vaccine-induced antibody responses is lacking. Antibody research is currently going through a big-data driven revolution, largely due to progress in next-generation sequencing (NGS) and bioinformatic analysis of antibody repertoires. A main advantage of high-throughput antibody repertoire analysis is that it provides a wealth of quantitative information not possible with other classical methods of antibody analysis (i.e., serum titers); this information includes: clonal distribution and diversity, somatic hypermutation patterns, and lineage tracing. In preliminary work my group has established standardized methods for antibody repertoire NGS, including an experimental-bioinformatic pipeline for error and bias correction that enables highly accurate repertoire sequencing and analysis. The overall goal of this proposal will be to apply high-throughput antibody repertoire analysis for quantitative vaccine profiling and discovery of next-generation immunodiagnostics. Using mouse subunit vaccination as our model system, we will answer for the first time, a fundamental biological question within the context of antibody responses - what is the link between genotype (antibody repertoire) and phenotype (serum antibodies)? We will expand upon this approach for improved rational vaccine design by quantitatively determining the impact of a comprehensive set of subunit vaccination parameters on complete antibody landscapes. Finally, we will develop advanced bioinformatic methods to discover immunodiagnostics based on antibody repertoire sequences. In summary, this proposal lays the foundation for fundamentally new approaches in the quantitative analysis of antibody responses, which long-term will promote the development of next-generation vaccines and immunodiagnostics.

1 492 586 €

Start date: 2016-06-01, End date: 2021-05-31

Charge and energy transfer are the key steps underlying most chemical reactions and biological transformations. The purely electronic dynamics that control such processes take place on attosecond time scales. A complete understanding of these dynamics on the electronic level therefore calls for new experimental methods with attosecond resolution that are applicable to aqueous environments. We propose to combine the element sensitivity of X-ray spectroscopy with attosecond temporal resolution and ultrathin liquid microjets to study electronic dynamics of relevance to chemical, biological and photovoltaic processes. We will build on our recent achievements in demonstrating femtosecond time-resolved measurements in the water, attosecond pho-toelectron spectroscopy on a liquid microjet and measuring and controlling attosecond charge migration in isolated molecules. We will first concentrate on liquid water to study its electronic dynamics following outer-valence ionization, the formation pathway of the solvated electron and the time scales and intermolecular Coulombic decay following inner-valence or core-level ionization. Second, we will turn to solvated species and measure electronic dynamics and charge migration in solvated molecules, transition-metal complexes and pho-toexcited nanoparticles. These goals will be achieved by developing several innovative experimental tech-niques. We will develop a source of isolated attosecond pulses covering the water window (285-538 eV) and combine it with a flat liquid microjet to realize attosecond transient absorption in liquids. We will complement these measurements with attosecond X-ray emission spectroscopy, Auger spectroscopy and a novel hetero-dyne-detected variant of resonant inelastic Raman scattering, exploiting the large bandwidth that is naturally available from attosecond X-ray sources.

2 750 000 €

Start date: 2018-04-01, End date: 2023-03-31

Lithium ion batteries offer tremendous potential as an enabling technology for sustainable transportation and development. However, their widespread usage as the energy storage solution for electric mobility and grid-level integration of renewables is impeded by the fact that current state-of-the-art lithium ion batteries have energy densities that are too small, charge- and discharge rates that are too low, and costs that are too high. Highly publicized instances of catastrophic failure of lithium ion batteries raise questions of safety. Understanding the limitations to battery performance and origins of the degradation and failure is highly complex due to the difficulties in studying interrelated processes that take place at different length and time scales in a corrosive environment. In the project, we will (1) develop and implement quantitative methods to study the complex interrelations between structure and electrochemistry occurring at the nano-, micron-, and milli-scales in lithium ion battery active materials and electrodes, (2) conduct systematic experimental studies with our new techniques to understand the origins of performance limitations and to develop design guidelines for achieving high performance and safe batteries, and (3) investigate economically viable engineering solutions based on these guidelines to achieve high performance and safe lithium ion batteries.

1 500 000 €

Start date: 2016-05-01, End date: 2021-04-30

What makes for a valuable and good life is a question that many people in the contemporary world ask themselves, yet it is one that social science research has seldom addressed. Only recently have scholars started undertaking inductive comparative research on different notions of the ‘good life’, highlighting socio-cultural variations and calling for a better understanding of the different imaginaries, aspirations and values that guide people in their quest for better living conditions. Research is still lacking, however, on how people themselves evaluate, compare, and put into perspective different visions of good living and their socio-cultural anchorage. This project addresses such questions from an anthropological perspective, proposing an innovative study of how ideals of the good life are articulated, (re)assessed, and related to specific places and contexts as a result of the experience of crisis and migration. The case studies chosen to operationalize these lines of enquiry focus on the phenomenon of return migration, and consist in an analysis of the imaginaries and experience of return by Ecuadorian and Cuban men and women who migrated to Spain, are dissatisfied with their life there, and envisage/carry out the project of going back to their countries of origin (Ecuador and Cuba respectively). The project’s ambition is to bring together and contribute to three main scholarly areas of enquiry: 1) the study of morality, ethics and what counts as ‘good life’, 2) the study of the field of economic practice, its definition, value regimes, and ‘crises’, and 3) the study of migratory aspirations, projects, and trajectories. A multi-sited endeavour, the research is designed in three subprojects carried out in Spain (PhD student), Ecuador (Post-Doc), and Cuba (PI), in which ethnographic methods will be used to provide the first empirically grounded study of the links between notions and experiences of crisis, return migration, and the (re)assessment of good living.

1 500 000 €

Start date: 2018-02-01, End date: 2023-01-31

Dietary fibres are recognized for their health promoting properties; nevertheless, many of the physicochemical mechanisms behind these effects remain poorly understood. While it is understood that dietary fibres can associate with small molecules influencing, both positively or negatively their absorption, the molecular mechanism, by which these associations take place, have yet to be elucidated We propose a study of the binding in soluble dietary fibres at a molecular level to establish binding constants for various fibres and nutritionally relevant ligands. The interactions between fibres and target compounds may be quite weak, but still have a major impact on the bioavailability. To gain insight to the binding mechanisms at a level of detail that has not earlier been achieved, we will apply novel combinations of analytical techniques (MS, NMR, EPR) and both natural as well as synthetic probes to elucidate the associations in these complexes from macromolecular to atomic level. Glucans, xyloglucans and galactomannans will serve as model soluble fibres, representative of real food systems, allowing us to determine their binding constants with nutritionally relevant micronutrients, such as monosaccharides, bile acids, and metals. Furthermore, we will examine supramolecular interactions between fibre strands to evaluate possible contribution of several fibre strands to the micronutrient associations. At the atomic level, we will use complementary spectroscopies to identify the functional groups and atoms involved in the bonds between fibres and the ligands. The proposal describes a unique approach to quantify binding of small molecules by dietary fibres, which can be translated to polysaccharide interactions with ligands in a broad range of biological systems and disciplines. The findings from this study may further allow us to predictably utilize fibres in functional foods, which can have far-reaching consequences in human nutrition, and thereby also public health.

1 500 000 €

Start date: 2016-04-01, End date: 2021-03-31

Given the increasing scarcity of suitable land for development, soil strengthening technologies have emerged in the past decade and go hand-in-hand with the implementation of the majority of foundation solutions. The goal is to alter the soil structure and its mechanical properties for ultimately securing the integrity of structures. The BIOGEOS project puts the focus on bio-mediated soil improvement, which falls within the broader framework of multi-physical processes in geo-mechanics. The goal of the project is to engineer a novel, natural material under controlled processes, for ultimately providing solutions to real problems in the geo-engineering and geo-energy fields by advancing knowledge around complex multi-physical phenomena in porous media. The bio-cemented geo-material, which is produced by carefully integrating the metabolic activity of native soil bacteria, is produced through the bio-mineralization of calcite bonds, which act as natural cementation for endowing the subsurface with real cohesion and increased resistance. A principal characteristic of the project is its multi-scale approach through advanced experimentation to identify the main physical mechanisms involved in the formation of the bio-mineralized bonds and their behaviour under mechanical loading. The development of such a bio-mediated technology will lead to innovative applications in a series of engineering problems such as the restoration of weak foundations, seismic retrofitting, erosion protection, and the enhancement of heat transfer in thermo-active geo-structures. The project foresees to adopt multiple loading conditions for its laboratory characterization and ultimately pass to the large experimental scale. BIOGEOS further aims to provide new knowledge around the way we perceive materials in relation with their micro-structure by implementing state-of-the-art inspection of the material’s structure in 3D space and subsequent prediction of their behaviour through numerical tools.

2 497 115 €

Start date: 2018-11-01, End date: 2023-10-31

During the past decades the PI has helped shape the research field of computer simulation of biomolecular systems at the atomic level. He has carried out one of the first molecular dynamics (MD) simulations of proteins, and has since then contributed many different methodological improvements and developed one of the major atomic-level force fields for simulations of proteins, carbohydrates, nucleotides and lipids. Methodology and force field have been implemented in a set of programs called GROMOS (GROningen MOlecular Simulation package), which is currently used in hundreds of academic and industrial research groups from over 50 countries on all continents. It is proposed to develop a next generation of molecular models, force fields, multi-scaling simulation methodology and software for biomolecular simulations which is at least an order of magnitude more accurate in terms of energetics, and which is 1000 times more efficient through the use of coarse-grained molecular models than the currently available software and models.

1 320 000 €

Start date: 2008-11-01, End date: 2014-09-30

Elementary particle physics is entering a spectacular new era in which experiments at the Large Hadron Collider (LHC) at CERN will soon start probing some of the deepest questions in physics, such as: Why is gravity so weak? Do elementary particles have substructure? What is the origin of mass? Are there new dimensions? Can we produce black holes in the lab? Could there be other universes with different physical laws? While the LHC pushes the energy frontier, the unprecedented precision of Atom Interferometry, has pointed me to a new tool for fundamental physics. These experiments based on the quantum interference of atoms can test General Relativity on the surface of the Earth, detect gravity waves, and test short-distance gravity, charge quantization, and quantum mechanics with unprecedented precision in the next decade. This ERC Advanced grant proposal is aimed at setting up a world-leading European center for development of a deeper theory of fundamental physics. The next 10 years is the optimal time for such studies to benefit from the wealth of new data that will emerge from the LHC, astrophysical observations and atom interferometry. This is a once-in-a-generation opportunity for making ground-breaking progress, and will open up many new research horizons.

2 200 000 €

Start date: 2009-05-01, End date: 2014-04-30

Materials with excellent diffusion barrier properties are highly relevant for packaging applications (food, pharmaceutics), sealing (car tires), protective encapsulation (microelectronics, photovoltaics, displays), and anticorrosive coatings (automotive). In all these fields of application, there is a strong technological demand for more effective, less costly, and environmentally benign solutions, which constitutes a significant business opportunity. The proposed project aims to develop novel barrier layers and anticorrosive coatings based on functionalized carbon nanosheets that are prepared from reactive, carbon-rich molecular precursors with chemical functional groups that provide surface-specific binding and adhesion. These materials combine the excellent barrier and anticorrosive properties of atomically dense carbon or inorganic thin film coatings with the tailored surface properties of monolayer coatings. Moreover, their preparation will be compatible with scalable and inexpensive solution-phase processing methods such as painting, spraying, or printing, followed by UV curing. The goal of the proposed project is to provide technology demonstrators for a diffusion barrier layer aimed at packaging applications, as well as for a wear-resistant, anti-corrosive coating on a metal surface.

149 500 €

Start date: 2016-02-01, End date: 2017-01-31

Understanding cause-effect relationships between variables is of great interest in many fields of science. However, causal inference from data is much more ambitious and difficult than inferring (undirected) measures of association such as correlations, partial correlations or multivariate regression coefficients, mainly because of fundamental identifiability problems. A main objective of the proposal is to exploit advantages from large-scale heterogeneous data for causal inference where heterogeneity arises from different experimental conditions or different unknown sub-populations. A key idea is to consider invariance or stability across different experimental conditions of certain conditional probability distributions: the invariants correspond on the one hand to (properly defined) causal variables which are of main interest in causality; andon the other hand, they correspond to the features for constructing powerful predictions for new scenarios which are unobserved in the data (new probability distributions). This opens novel perspectives: causal inference can be phrased as a prediction problem of a certain kind, and vice versa, new prediction methods which work well across different scenarios (unobserved in the data) should be based on or regularized towards causal variables. Fundamental identifiability limits will become weaker with increased degree of heterogeneity, as we expect in large-scale data. The topic is essentially unexplored, yet it opens new avenues for causal inference, structural equation and graphical modeling, and robust prediction based on large-scale complex data. We will develop mathematical theory, statistical methodology and efficient algorithms; and we will also work and collaborate on major application problems such as inferring causal effects (i.e., total intervention effects) from gene knock-out or RNA interference perturbation experiments, genome-wide association studies and novel prediction tasks in economics.

2 184 375 €

Start date: 2018-10-01, End date: 2023-09-30

Centrosome duplication entails the formation of a single procentriole next to each centriole once per cell cycle. The mechanisms governing procentriole formation are poorly understood and constitute a fundamental open question in cell biology. We will launch an innovative multidisciplinary research program to gain significant insight into these mechanisms using C. elegans and human cells. This research program is also expected to have a significant impact by contributing important novel assays to the field. Six specific aims will be pursued: 1) SAS-6 as a ZYG-1 substrate: mechanisms of procentriole formation in C. elegans. We will test in vivo the consequence of SAS-6 phosphorylation by ZYG-1. 2) Biochemical and structural analysis of SAS-6-containing macromolecular complexes (SAMACs). We will isolate and characterize SAMACs from C. elegans embryos and human cells, and analyze their structure using single-particle electron microscopy. 3) Novel cell-free assay for procentriole formation in human cells. We will develop such an assay and use it to test whether SAMACs can direct procentriole formation and whether candidate proteins are needed at centrioles or in the cytoplasm. 4) Mapping interactions between centriolar proteins in live human cells. We will use chemical methods developed by our collaborators to probe interactions between HsSAS-6 and centriolar proteins in a time- and space-resolved manner. 5) Functional genomic and chemical genetic screens in human cells. We will conduct high-throughput fluorescence-based screens in human cells to identify novel genes required for procentriole formation and small molecule inhibitors of this process. 6) Mechanisms underlying differential centriolar maintenance in the germline. In C. elegans, we will characterize how the sas-1 locus is required for centriole maintenance during spermatogenesis, as well as analyze centriole elimination during oogenesis and identify components needed for this process

2 004 155 €

Start date: 2009-04-01, End date: 2014-03-31

Chemotherapy, often given in conjunction with other therapies is infamous for its off target associated side effects. Recent studies have shown that drugs combinations can act synergistically at certain ratios and are more effective and less toxic than single drug therapies. Despite promising in vitro results, combination drug therapy for Oncology has not been successfully translated to the clinic due to lack of efficient delivery systems that can maintain the desired synergistic drug concentrations in the body as each drug has a different pharmacokinetics and toxicity profile. The objective of this project is to develop a universal platform for simultaneous delivery of multiple drugs to specific cells in vivo using a protein cage that was developed in our laboratory for encapsulation of diverse cargoes.

150 000 €

Start date: 2017-11-01, End date: 2019-04-30

The simulation of Partial Differential Equations (PDEs) is an indispensable tool for innovation in science and technology. Computer-based simulation of PDEs approximates unknowns defined on a geometrical entity such as the computational domain with all of its properties. Mainly due to historical reasons, geometric design and numerical methods for PDEs have been developed independently, resulting in tools that rely on different representations of the same objects. CHANGE aims at developing innovative mathematical tools for numerically solving PDEs and for geometric modeling and processing, the final goal being the definition of a common framework where geometrical entities and simulation are coherently integrated and where adaptive methods can be used to guarantee optimal use of computer resources, from the geometric description to the simulation. We will concentrate on two classes of methods for the discretisation of PDEs that are having growing impact: isogeometric methods and variational methods on polyhedral partitions. They are both extensions of standard finite elements enjoying exciting features, but both lack of an ad-hoc geometric modelling counterpart. We will extend numerical methods to ensure robustness on the most general geometric models, and we will develop geometric tools to construct, manipulate and refine such models. Based on our tools, we will design an innovative adaptive framework, that jointly exploits multilevel representation of geometric entities and PDE unknowns. Moreover, efficient algorithms call for efficient implementation: the issue of the optimisation of our algorithms on modern computer architecture will be addressed. Our research (and the team involved in the project) will combine competencies in computer science, numerical analysis, high performance computing, and computational mechanics. Leveraging our innovative tools, we will also tackle challenging numerical problems deriving from bio-mechanical applications.

2 199 219 €

Start date: 2016-10-01, End date: 2021-09-30

A large social science literature tries to describe and understand the causes and consequences of crime, usually focusing on individuals’ criminal activity in isolation. The ambitious aim of this research project is to establish a broader perspective of crime that takes into account the social context in which it takes place. The findings will inform policymakers on how to better use funds both for crime prevention and the rehabilitation of incarcerated criminals. Criminal activity is often a group phenomenon, yet little is known about how criminal networks form and what can be done to break them up or prevent them from forming in the first place. Overlooking victims of crime and their relationships to criminals has led to an incomplete and distorted view of crime and its individual and social costs. While a better understanding of these social interactions is crucial for designing more effective anti-crime policy, existing research in criminology, sociology and economics has struggled to identify causal effects due to data limitations and difficult statistical identification issues. This project will push the research frontier by combining register datasets that have never been merged before, and by using several state-of-the-art statistical methods to estimate causal effects related to criminal peer groups and their victims. More specifically, we aim to do the following: -Use recent advances in network modelling to describe the structure and density of various criminal networks and study network dynamics following the arrest/incarceration or death of a central player in a network. -Obtain a more accurate measure of the societal costs of crime, including actual measures for lost earnings and physical and mental health problems, following victims and their offenders both before and after a crime takes place. -Conduct a randomized controlled trial within a prison system to better understand how current rehabilitation programs affect criminal and victim networks.

1 187 046 €

Start date: 2018-03-01, End date: 2023-02-28

The goal of this project is to explore the fundamental processes which trigger the nucleation and growth of solids. Condensed matter is formed by clustering of atoms, ions or molecules. This initial step is key for the onset of crystallization, condensation and precipitate formation. Yet, despite of the scientific and technological significance of these phenomena, on an atomistic level we merely have expectations on how atoms should behave rather than experimental evidence about how the growth of solid matter is initiated. The classical nucleation theory is commonly in agreement with experiments, provided the original and the final stages are inspected qualitatively. However, the classical theory does not define what fundamentally constitutes a pre-nucleation state or how a nucleus is formed at all. CLUSTER aims at investigating the very early stages of crystalline matter formation on an unprecedented length scale. It shall explore the atomic mechanisms which prompt the formation of solids. Complemented by density functional theory calculations and molecular dynamics simulations, in-situ high-resolution electron microscopy shall be used to investigate the formation, dynamics, stability and evolution of tiniest atomic clusters which represent the embryos of solid matter. Firstly, we investigate the 3D structure of clusters deposited on suspended graphene. Secondly, we focus on cluster formation, the evolution of sub-critical nuclei and the onset of particle growth by thermal activation. Thirdly, using a novel liquid-cell approach in the transmission electron microscope, we control and monitor in-situ cluster formation and precipitation in supersaturated solutions. The results of CLUSTER, which will advance the understanding of the birth of solid matter, are important for the controlled synthesis of (nano-)materials, for cluster science and catalysis and for the development of novel materials.

2 271 250 €

Start date: 2016-06-01, End date: 2021-05-31

"""First principles"" and ""bottom-up"" have become buzz words across scientific and engineering disciplines when it comes to the discovery, prediction and understanding of material properties and their link to processing and microstructure. Reality, however, teaches us that in the foreseeable future computational resources will be insufficient to apply predictive techniques such as quantum mechanics or atomistics to the technologically most relevant length and time scales - far above nanometers and nanoseconds. This proposal aims for nothing less but the seemingly impossible: the application of atomistic techniques to problems occurring over microns to millimeters and seconds to minutes. Instead of relying on computational power, this will be achieved by a combination of scale-bridging methodologies (involving the PI's nonlocal and meshless quasicontinuum techniques, concepts from particle methods, continuum and statistical mechanics) and computational science strategies in order to produce new theory and an open-source, computational toolset for long-term, large-scale simulations relying solely on atomistic input. Spatial upscaling, temporal upscaling as well as heat and mass transfer will be addressed. Enabled by the new scale-bridging capabilities, two representative, open challenges will be investigated: recrystallization in magnesium during thermo-mechanical processing and corrosion in steel by hydrogen embrittlement. Both are of enormous technological and economic importance but current techniques are insufficient to bridge the gap between the macroscopic mechanical performance, microstructural mechanisms and predictive atomic-scale simulations. The outcomes of this five-year research program will provide never-before techniques and numerical tools to catalyze a user community across science and technology. Although the focus is on metals, several of the proposed techniques are applicable to a significantly wider range of materials and applications."

1 995 128 €

Start date: 2018-03-01, End date: 2023-02-28

Entropy (admissible) weak solutions are widely considered to be the standard solution framework for hyperbolic systems of conservation laws and incompressible Euler equations. However, the lack of global existence results in several space dimensions, the recent demonstration of non-uniqueness of these solutions and computations showing the lack of convergence of state of the art numerical methods to them, have reinforced the need to seek alternative solution paradigms. Although one can show that numerical approximations of these nonlinear PDEs converge to measure-valued solutions i.e Young measures, these solutions are not unique and we need to constrain them further. Statistical solutions i.e, time-parametrized probability measures on spaces of integrable functions, are a promising framework in this regard as they can be characterized as a measure-valued solution that also contains information about all possible multi-point spatial correlations. So far, well-posedness of statistical solutions has been shown only in the case of scalar conservation laws. The main aim of the proposed project is to analyze statistical solutions of systems of conservation laws and incompressible Euler equations and to design efficient numerical approximations for them. We aim to prove global existence of statistical solutions in several space dimensions, by showing convergence of these numerical approximations, and to identify suitable additional admissibility criteria for statistical solutions that can ensure uniqueness. We will use these numerical methods to compute statistical quantities of interest and relate them to existing theories (and observations) for unstable and turbulent fluid flows. Successful completion of this project aims to establish statistical solutions as the appropriate solution paradigm for inviscid fluid flows, even for deterministic initial data, and will pave the way for applications to astrophysics, climate science and uncertainty quantification.

1 959 323 €

Start date: 2018-08-01, End date: 2023-07-31

The goal of this project is to study conformally invariant fractal structures from the perspectives of analysis, dynamics, probability, geometry and physics, emphasizing interrelations of these fields. In the last two decades such structures emerged in several areas: continuum scaling limits of 2D critical models in statistical physics (percolation, Ising model); extremal configurations for various problems in complex analysis (multifractal harmonic measures, coefficient growth of univalent maps, Brennan's conjecture); chaotic sets for complex dynamical systems (Julia sets, Kleinian groups). Capitalizing on recent successes, I plan to continue my work in these areas, exploiting their interactions and connections to physics. I intend to achieve at least some of the following goals: * To establish that several critical lattice models have conformally invariant scaling limits, by building upon results on percolation and Ising models and finding discrete holomorphic observables. * To study geometric properties of arising fractal curves and random fields by connecting them to Schramm's SLE curves and Gaussian Free Fields. * To investigate massive scaling limits by describing them geometrically with generalizations of SLEs. * To lay mathematical framework behind relevant physical notions, such as Coulomb Gas (by relating height functions to GFFs) and Quantum Gravity (by identifying limits of random planar graphs with Liouville QGs). * To improve known bounds in several old questions in complex analysis by studying multifractal spectra of harmonic measures. * To estimate extremal behavior of such spectra by using holomorphic motions of (quasi) conformal maps and thermodynamic formalism. * To understand nature of extremal multifractals for harmonic measure by studying random and dynamical fractals. The topics involved range from century old to very young ones. Recently connections between them started to emerge, opening exciting possibilities for new developments in some long standing open problems.

1 278 000 €

Start date: 2009-01-01, End date: 2013-12-31

Networks are the backbone of our society, but configuring them is error-prone and tedious: misconfigured networks result in headline grabbing network outages that affect many users and hurt company revenues while security breaches that endanger millions of customers. There are currently no guarantees that deployed networks correctly implement their operator’s policy. Existing research has focused on two directions: a) low level analysis and instrumentation of real networking code prevents memory bugs in individual network elements, but does not capture network-wide properties desired by operators such as reachability or loop freedom; b) high-level analysis of network-wide properties to verify operator policies on abstract network models; unfortunately, there are no guarantees that the models are an accurate representation of the real network code, and often low-level errors invalidate the conclusions of the high-level analysis. We propose to achieve provably correct networks by simultaneously targeting both low-level security concerns and network-wide policy compliance checking. Our key proposal is to rely on exhaustive network symbolic execution for verification and to automatically generate provably correct implementations from network models. Generating efficient code that is equivalent to the model poses great challenges that we will address with three key contributions: a) We will develop a novel theoretical equivalence framework based on symbolic execution semantics, as well as equivalence-preserving model transformations to automatically optimize network models for runtime efficiency. b) We will develop compilers that take network models and generate functionally equivalent and efficient executable code for different targets (e.g. P4 and C). c) We will design algorithms that generate and insert runtime guards that ensure correctness of the network with respect to the desired policy even when legacy boxes are deployed in the network.

1 325 000 €

Start date: 2018-01-01, End date: 2022-12-31

Spectroscopic investigation of high (n >>20) molecular Rydberg states below and above the first adiabatic ionization threshold will be carried out with the aims of 1) obtaining fully resolved information on the vibrational, rotational, spin-orbit and hyperfine structures of these highly excited electronic states, 2) characterizing the role of nuclear spins in molecular photoionization, 3) determining the hyperfine structure of fundamental molecular cations at kHz resolution and accuracy by Rydberg series extrapolation, 4) measuring intervals between rovibrational levels of these molecular cations at sub MHz precision, 5) gaining a complete understanding, and providing an adequate description and classification, of angular momentum coupling (including nuclear spins) in high molecular Rydberg states, 6) testing theoretical predictions of the energy level structure of Rydberg molecules by ab initio multichannel quantum defect theory (MQDT) and of the rotational, vibrational and hyperfine levels of molecular cations by ab initio quantum chemistry and QED. The spectroscopic measurements using tunable narrow-band vacuum-ultraviolet and millimeter wave radiation sources will be performed on cold samples in supersonic beams as well as on trapped samples of translationally cold Rydberg atoms and molecules. To this end, our recent approach to trap H atoms in Rydberg states electrostatically (Hogan and Merkt, Phys. Rev. Lett. 100, 043001 (2008)) will be extended to molecules, and the possibility of transfering the trapped species from electrostatic traps to magnetic and optical traps will be explored.

1 192 395 €

Start date: 2008-11-01, End date: 2013-10-31

We address a fundamental and increasingly important challenge in computer science: how to program large-scale heterogeneous parallel computers. Society relies on these computers to satisfy the growing demands of important applications such as drug design, weather prediction, and big data analytics. Architectural trends make heterogeneous parallel processors the fundamental building blocks of computing platforms ranging from quad-core laptops to million-core supercomputers; failing to exploit these architectures efficiently will severely limit the technological advance of our society. Computationally demanding problems are often inherently parallel and can readily be compiled for various target architectures. Yet, efficiently mapping data to the target memory system is notoriously hard, and the cost of fetching two operands from remote memory is already orders of magnitude more expensive than any arithmetic operation. Data access cost is growing with the amount of parallelism which makes data layout optimizations crucial. Prevalent parallel programming abstractions largely ignore data access and guide programmers to design threads of execution that are scheduled to the machine. We depart from this control-centric model to a data-centric program formulation where we express programs as collections of values, called memlets, that are mapped as first-class objects by the compiler and runtime system. Our holistic compiler and runtime system aims to substantially advance the state of the art in parallel computing by combining static and dynamic scheduling of memlets to complex heterogeneous target architectures. We will demonstrate our methods on three challenging real-world applications in scientific computing, data analytics, and graph processing. We strongly believe that, without holistic data-centric programming, the growing complexity and inefficiency of parallel programming will create a scaling wall that will limit our future computational capabilities.

1 499 672 €

Start date: 2016-06-01, End date: 2021-05-31

Adhesives that debond-on-demand through application of an external stimulus are highly relevant for manufacturing (semiconductor, automotive, aerospace, construction, packaging, sportswear), healthcare applications (wound dressing, transdermal patches), and numerous other domains, and they can significantly contribute to the sustainable use of materials (repairing, reworking, recycling). In all cases, there is a technological need for effective and environmentally benign solutions that provide secure adhesion during use, while also permitting for a simple and clean separation of bonded parts “on command” without the need for additional complex process steps. The proposed project aims to develop new debond-on-demand adhesives based on the combination of low-molecular weight functional polymers and light-responsive degradable cross-linking agents. The new materials are expected to combine optimal adhesive properties for a wide range of substrates with a new mechanism that enables straightforward and efficient, ultraviolet light-induced debonding at ambient temperature. The debonding mechanism involves two different effects that are combined in a synergistic manner: the controlled degradation of the cross-linker transforms polymer networks into low-molecular weight polymers, and the simultaneous release of nitrogen gas “propels” the bonded parts away from each other. The degraded polymer residues can be easily removed and clean debonded components are furnished. The overarching goals of the proposed project are to bridge the gap between scientific discovery and implementation by (i) providing a better understanding for the mechanism at play; (ii) demonstrating the effect in a variety of adhesive platforms based on polymers that are employed in current adhesive technologies; and (iii) providing technology demonstrators for pressure-sensitive adhesive tapes and cold-cured two-component adhesives with debond-on-demand properties.

149 250 €

Start date: 2016-06-01, End date: 2017-05-31

Tax evasion leads to billions of Euros of losses in government revenue around the world. This does not only affect public budgets, but can also create large distortions between activities that are fully taxed and others that escape taxation through evasion. These issues are particularly severe in developing countries, where evasion is especially high and governments struggle to raise funds for basic services and infrastructure, while at the same time trying to grow independent of international aid. It is widely suspected that some of the most common and difficult to detect forms of evasion involve interactions across firm networks. However, due to severe data limitations, the existing literature has mostly considered taxpayers as isolated units. Empirical evidence on tax compliance in firm networks is extremely sparse. This proposal describes 3 Sub-Projects to fill this gap. They are made possible thanks to access I have obtained -through five years of prior research and policy engagement– to unique datasets from Chile and Ecuador on both the networks of supply chains and of joint ownership structures. The first Sub-Project focuses on international firm networks. It aims to analyze profit shifting of multinational firms to low tax jurisdictions, exploiting a natural experiment in Chile that strongly increased monitoring of international tax norms. The second Sub-Project investigates the analogous issue at the intranational level: profit shifting and tax collusion in networks of firms within the same country. Despite much anecdotal evidence, this behavior has received little rigorous empirical scrutiny. The final Sub-Project is situated at the nexus between international and national firms. It seeks to estimate a novel form of spillovers of FDI: the impact on tax compliance of local trading partners of foreign-owned firms. DEVTAXNET will provide new insights about the role of firm networks for tax evasion that are valuable to academics and policy makers alike.

1 288 125 €

Start date: 2018-01-01, End date: 2022-12-31

In the past decade, artificial metalloenzymes (AMs) have emerged as an attractive alternative to the more traditional enzymes and homogeneous catalysts. Such hybrid catalysts result from the incorporation of an abiotic metal cofactor within a macromolecule (protein or oligonucleotide). Artificial metalloenzymes combine attractive features of both homogeneous catalysts and enzymes, including the possibility to genetically optimize the catalytic performance of new-to-nature organometallic reactions. Can artificial metalloenzymes become as catalytically efficient as naturally-evolved metalloenzymes, even in complex biological mixtures? Herein, we outline our efforts to address this challenge by localizing and evolving AMs within the periplasm of Escherichia coli. To achieve this objective, we will exploit AMs based on the biotin-streptavidin technology. Four subprojects have been tailored to address the challenges: i) knock-out deleterious components present in the periplasm; ii) improve the cofactor uptake through the outer-membrane; iii) engineer streptavidin to boost the AM’s performance; and iv) rely both on screening and selection strategies to evolve AMs in vivo. Relying on auxotrophs, we will demonstrate the potential of AMs to complement metabolic pathways. Only E. coli auxotrophs containing an evolved AM capable of producing the vital aminoacid-precursor will survive the stringent selection pressure. We have identified several selectable aminoacid precursors which can be produced by metathesis (indole, precursor of tryptophan), enone reduction (keto valine, precursor of valine) and allylic substitution (prephenate, precursor of tyrosine and phenylalanine). In a Darwinian evolution spirit, we anticipate that applying selection pressure will allow to evolve AMs to unprecedented catalytic performance. The main deliverable of the DrEAM is an engineered and evolvable E. coli strain capable of performing in vivo reaction cascades combining AMs and natural enzymes.

2 490 700 €

Start date: 2016-10-01, End date: 2021-09-30

Here we present an original design of a compact and portable set-up able to generate very broadband (70-100 nm at 300 nm) and powerful (>1uJ/pulse) ultrashort deep-UV pulses. Compared with other schemes, it guarantees an aberration-free propagation, an easy installation and minimal dispersion. The present project aims to bring the current prototype to the level of a commercial device. The conceived design will allow to manufacture a compact, portable and cost effective device, which will be user-friendly and with almost no required maintenance. There is no such a source commercially available and the schemes proposed in scientific literature require an advanced level of competence in optics and laser physics, are not cost effective and unsuitable for industrial applications. There is thus a need of sources for ultrafast broadband radiation in the deep-UV to advance and enable new ultrafast science and extend into this spectral range the technological application of ultrafast laser sources. The implementation of the proposed device will definitively fill this gap.

140 625 €

Start date: 2018-01-01, End date: 2019-06-30

E-DURA aims to assess the commercial viability of a new class of soft, multimodal neural implants called e-dura. Current technologies are rigid and present physical, electrochemical and biological mismatches that prevent prolonged periods of implantation. Our technology represents a significant improvement over state-of-art on all those criteria. Moreover, our extensive network of academics and industry professionals represents an advantage in commercializing e-dura, thereby addressing a market estimated to reach 11.8 billion Euro by 2020. Within E-DURA, we will prototype a device suitable for human implantation and build the business case around our innovation.

149 994 €

Start date: 2018-09-01, End date: 2020-02-29

In the face of the alarming pace of recent environmental change we lack the tools to accurately predict how biodiversity and ecosystem services will respond. One key gap in knowledge that limits our predictive ability is uncertainty concerning how the biotic interactions will change. Developing a predictive science of species interactions requires integrating evolutionary, biogeographic and ecological mechanisms acting at different spatial and temporal scales. We will use a hierarchical cross-scale approach, combining phylogeography, network ecology, statistical modelling and experiments, to disentangle the mechanisms governing species richness and mutualistic interactions in tropical hummingbirds and their food plants. Hummingbirds and their food plants are an excellent model system because they are highly diverse, highly specialized, and logistically feasible to study. Our objectives are to (1) evaluate the influence of factors, such as trait-matching, environmental conditions and relatedness, on network structure; (2) quantify how and why interaction beta-diversity (i.e., reflecting the change in both species composition, and in interacting partners) changes across elevation gradients in each of three biogeographic regions with distinct evolutionary histories (mountain regions in Costa Rica, Ecuador, Brazil); (3) evaluate the importance of multiple factors, such as trait-matching, environmental conditions, relatedness and abundance, on species interactions and network structure; and (4) develop a predictive model of species interactions and evaluate its performance using cross-validation and experimentation. Together, these tasks will provide new insight into one of the central enigmas in ecology, namely, why species diversity and its interaction architecture change across space and time. We will also be able predict how species interactions will change from present to the future, which is essential for the conservation of biodiversity and ecosystem services.

2 499 930 €

Start date: 2018-10-01, End date: 2023-09-30

Man and man-made electronic systems share the same ecosystem, and yet work radically differently. Human metabolism uses ion gradients across insulated membranes to simultaneously process slow analog chemical reactions and communicate information in multicellular systems via soluble/volatile molecular signals. By contrast, electronic systems use multicore central processing units to control the flow of electrons through insulated metal wires with gigahertz frequency and communicate information across networks via wired/wireless connections. With the advent of the internet of things, networks of interconnected electronic devices will reach the processing complexity of living systems, yet they remain largely incompatible with biological systems. Wearable electronics can profile physical parameters such as steps and heartbeat, and Google’s proposal to develop glucose-monitoring contact lenses has triggered a wave of interest in harnessing the full potential of bioelectronics for medical applications. Yet this vision remains limited to diagnostics. Capitalizing on our mind-controlled and smartphone-adjustable optogenetic drug-dosing devices, ElectroGene will establish the foundations of electrogenetics, the science of creating electro-genetic interfaces that enable direct two-way communication between electronic devices and living cells. ElectroGene consists of three pillars, (i) voltage-triggered gene expression, (ii) genetically programmed electronics and (iii) wireless-powered implants providing closed-loop bioelectronic control, which allow real-time monitoring of metabolic conditions (diagnosis), enable remote-controlled production and dosing of protein therapeutics by implanted designer cells (treatment), and manage closed-loop control between cells and electronics, thus linking diagnosis and therapy to block disease onset (prevention). ElectroGene design principles and devices will be validated in proof-of-concept preclinical studies for the treatment of diabetes.

2 500 000 €

Start date: 2018-11-01, End date: 2023-10-31

Neural oscillations are ubiquitous in the human brain and have been implicated in diverse cognitive functions to support both neural communication and plasticity. Their functional relevance is further supported by a large number of studies linking various cognitive deficits (e.g., attention deficit hyperactivity disorder, ADHD) with abnormal neural oscillations. However, this field of research faces two important problems: First, there is only correlative, but no causal evidence linking cognitive deficits to abnormal neural oscillations in humans. Second, there is virtually no theory-driven mechanistic approach that generates insights into how oscillations within and across neural networks are linked to human behavior. In this project, I propose to take decisive steps to provide a long-needed neurophysiological characterization—via (1) computational modelling, (2) electrophysiological measures, and (3) novel non-invasive manipulations of cortical rhythms—on how neural oscillations contribute to two types of cognitive processes that are fundamental for many aspects of human behavior: attention and short-term memory. I will go a step further by demonstrating that it is possible to augment performance in these cognitive functions with the design of non-invasive brain stimulation protocols individually tailored to the theory-driven neurocomputational characterizations and electrophysiological signatures of each individual. This will result in the applied goal of deriving new neuro-computational assays that can detect deviant network interactions causally related to cognitive functions, which is key for then renormalizing those functions in neuropsychological conditions such as ADHD. Thus, if successful, my proposed work will ultimately result in novel, low-cost, and painless non-invasive neural interventions for a wide range of neuropsychological disorders tied to abnormal neural oscillations.

1 497 104 €

Start date: 2018-02-01, End date: 2023-01-31

The purpose of this proposal is to investigate from various perspectives some equidistribution problems associated with homogeneous spaces of arithmetic type: a typical problem (basically solved) is the distribution of the set of representations of a large integer by an integral quadratic form. Another harder problem is the study of the distribution of special points on Shimura varieties. In a different direction (linked with quantum chaos), the study of the concentration of Laplacian (Maass) eigenforms or of sections of holomorphic bundles is related to similar problems. Given X such a space and G>L the underlying algebraic group and its corresponding lattice L, the above questions boil down to studying the distribution of H-orbits x.H (or more generally H-invariant measures)on the quotient L\G for some subgroups H. This question may be studied different methods: Harmonic Analysis (HA): given a function f on L\G one studies the period integral of f along x.H. This may be done by automorphic methods. In favorable circumstances, the above periods are related to L-functions which one may hope to treat by methods from analytic number theory (the subconvexity problem). Ergodic Theory (ET): one studies the properties of weak*-limits of the measures supported by x.H using rigidity techniques: depending on the nature of H, one might use either rigidity of unipotent actions or the more recent rigidity results for torus actions in rank >1. In fact, HA and ET are intertwined and complementary : the use of ET in this context require a substantial input from number theory and HA, while ET lead to a soft understanding of several features of HA. In addition, the Langlands correspondence principle make it possible to pass from one group G to another. Based on earlier experience, our goal is to develop these interactions systematically and to develop new approaches to outstanding arithmetic problems :eg. the subconvexity problem or the Andre/Oort conjecture.

866 000 €

Start date: 2008-12-01, End date: 2013-11-30

The aim of this project is to understand the causal factors contributing to the cognitive decline during senescence and to develop sensitive and standardized behaviour tests for early detection in order to increase the welfare of affected species. With the rapidly ageing population of Europe, related research is a priority in the European Union. We will focus both on characterising the ageing phenotype and the underlying biological processes in dogs as a well-established natural animal model. We develop a reliable and valid test battery applying innovative multidisciplinary methods (e.g. eye-tracking, motion path analysis, identification of behaviour using inertial sensors, EEG, fMRI, candidate gene, and epigenetics) in both longitudinal and cross-sectional studies. We expect to reveal specific environmental risk factors which hasten ageing and also protective factors which may postpone it. We aim to provide objective criteria (behavioural, physiological and genetic biomarkers) to assess and predict the ageing trajectory for specific individual dogs. This would help veterinarians to recognise the symptoms early, and initiate necessary counter actions. This approach establishes the framework for answering the broad question that how we can extend the healthy life of ageing dogs which indirectly also contributes to the welfare of the owner and decreases veterinary expenses. The detailed description of the ageing phenotype may also facilitate the use of dogs as a natural model for human senescence, including the development and application of pharmaceutical interventions. We expect that our approach offers the scientific foundation to delay the onset of cognitive ageing in dog populations by 1-2 years, and also increase the proportion of dogs that enjoy healthy ageing.

1 202 500 €

Start date: 2016-06-01, End date: 2021-05-31

The project provides a comprehensive and groundbreaking approach to the analysis of the moral mind and inequality acceptance. The first part of the project will provide a novel study of how the moral ideals of personal responsibility and individual freedom, which are fundamental values in most liberal societies, shape inequality acceptance. It will also provide the first experimental study of how people draw the moral circle, which is at the heart of the most pressing policy challenges facing the world today and strongly related to the question of global fairness. The second part will study how social institutions shape inequality acceptance and how it develops in childhood and adolescence, by providing two unique international studies of inequality acceptance in 60 countries across the world. These studies will provide novel insights on the distributive behavior of nationally representative samples of adults and children and on the cultural transmission of moral preferences in society. The project is rooted in behavioral and experimental economics, but will also draw on insights from other social sciences and philosophy. It will develop novel experimental paradigms to study the moral mind and the nature of inequality acceptance, including incentivized experiments on nationally representative populations, and combine structural and non-parametric empirical analysis with theory development. Taken together, the project represents a unique study of inequality acceptance in the social sciences that will address an important knowledge gap in the literature on inequality.

2 500 000 €

Start date: 2018-10-01, End date: 2023-09-30

Due to sensory loss diabetic patients are prone to falls and to foot ulcers, which consequently increase the risk of amputations. Because of the lack of sensory feedback amputees experience falls, perceive the prosthesis as a foreign body and therefore do not rely on it during walking. This causes counterbalancing movements that increase fatigue. Both types of patients suffer neuropathic pain, associable to aberrant sensory inputs. Neural pathways between the periphery and the brain are still functional above the damage or the amputation. Targeting these structures with peripheral neural interfaces could allow the restoration of natural sensory functionalities. The aim of project is to develop the first neuroprosthesis restoring natural foot sensations, through sciatic nerve stimulation, to patients with diabetic neuropathy or leg amputation. To that aim we will develop a detailed computational model of the sensory loop of the sciatic nerve. It will merge the electrical stimulation effects on sensory fibers and transduction of mechanical deformations of the skin into action potentials. Modelling results will be validated. Applying this modeling framework we will optimize the geometry of a peripheral neural interface, its surgical placement and define stimulation protocols that mimic natural sensory feedback responses. Effective device for feedback restoration will be constructed, able to translate the signals recorded by sensorized sole placed under the prosthetic or diabetic foot into the natural foot sensations perceived by subject. The interventional tools for embodiment boosting and pain relief will be developed. Clinical tests on amputee and diabetic subjects will assess the efficacy of the FeelAgain conceptual and technological framework by examination of pain, embodiment, ulcer prevention, falls avoidance and walking ability.

1 499 637 €

Start date: 2018-04-01, End date: 2023-03-31

Since the pioneering works of Black & Scholes, Merton and Markowitch, sophisticated quantitative methods are being used to introduce more complex financial products each year. However, this exciting increase in the complexity forces the industry to engage in proper risk management practices. The recent financial crisis emanating from risky loan practices is a prime example of this acute need. This proposal focuses exactly on this general problem. We will develop mathematical techniques to measure and assess the financial risk of new instruments. In the theoretical direction, we will expand the scope of recent studies on risk measures of Artzner et-al., and the stochastic representation formulae proved by the principal investigator and his collaborators. The core research team consists of mathematicians and the finance faculty. The newly created state-of-the-art finance laboratory at the host institution will have direct access to financial data. Moreover, executive education that is performed in this unit enables the research group to have close contacts with high level executives of the financial industry. The theoretical side of the project focuses on nonlinear partial differential equations (PDE), backward stochastic differential equations (BSDE) and dynamic risk measures. Already a deep connection between BSDEs and dynamic risk measures is developed by Peng, Delbaen and collaborators. Also, the principal investigator and his collaborators developed connections to PDEs. In this project, we further investigate these connections. Chief goals of this project are theoretical results and computational techniques in the general areas of BSDEs, fully nonlinear PDEs, and the development of risk management practices that are acceptable by the industry. The composition of the research team and our expertise in quantitative methods, well position us to effectively formulate and study theoretical problems with financial impact.

880 560 €

Start date: 2008-12-01, End date: 2013-11-30

The development of advanced photon-based technologies offers exciting promises in fields of crucial importance for the development of sustainable societies such as energy and food management, security and health care. Innovative photonic devices will however reveal their true potential if we can deploy their functionalities not only on rigid wafers, but also over large-area, flexible and stretchable substrates. Indeed, providing energy harvesting, sensing, or stimulating abilities over windows, screens, food packages, wearable textiles, or even biological tissues will be invaluable technological breakthroughs. Today, however, conventional fabrication approaches remain difficult to scale to large area, and are not well adapted to the mechanical and topological requirements of non-rigid and curved substrates. In FLOWTONICS, we propose innovative materials processing approaches and device architectures to enable the simple and scalable fabrication of nano-structured photonic systems compatible with flexible and stretchable substrates. Our strategy is to direct the flow of optical materials through an innovative and thus far unexplored exploitation of the solid-state dewetting and thermal drawing processes. Our objectives are three-fold: (1) Study and demonstrate, for the first time, the strong potential of the dewetting of chalcogenide glasses layers for the fabrication of large area photonic devices; (2) Show that dewetting can also be exploited to realize photonic architectures onto engineered, nano-imprinted flexible and stretchable polymer substrates; (3) Demonstrate, for the first time, the use of the thermal drawing process as a novel tool to realize advanced flexible and stretchable photonic ribbons and fibers. These novel approaches can contribute to game-changing scientific and technological advances for the sustainable management of our resources and to meet our growing health care needs, putting Europe at the forefront of innovation in these crucial areas.

1 499 585 €

Start date: 2016-02-01, End date: 2021-01-31

Our astonishing cognitive abilities are the consequence of complex connectivity within our neuronal networks and the large functional diversity of excitable nerve cells and their synapses. Investigations over the past half a century revealed dramatic diversity in shape, size and functional properties among synapses established by distinct cell types in different brain regions and demonstrated that the functional differences are partly due to different molecular mechanisms. However, synaptic diversity is also observed among synapses established by molecularly and morphologically uniform presynaptic cells on molecularly and morphologically uniform postsynaptic cells. Our hypothesis is that quantitative molecular differences underlie the functional diversity of such synapses. We will focus on hippocampal CA1 pyramidal cell (PC) to mGluR1α+ O-LM cell synapses, which show remarkable functional and molecular heterogeneity. In vitro multiple cell patch-clamp recordings followed by quantal analysis will be performed to quantify well-defined biophysical properties of these synapses. The molecular composition of the functionally characterized single synapses will be determined following the development of a novel postembedding immunolocalization method. Correlations between the molecular content and functional properties will be established and genetic up- and downregulation of individual synaptic proteins will be conducted to reveal causal relationships. Finally, correlations of the activity history and the functional properties of the synapses will be established by performing in vivo two-photon Ca2+ imaging in head-fixed behaving animals followed by in vitro functional characterization of their synapses. Our results will reveal quantitative molecular fingerprints of functional properties, allowing us to render dynamic behaviour to billions of synapses when the connectome of the hippocampal circuit is created using array tomography.

2 498 750 €

Start date: 2018-10-01, End date: 2023-09-30

Gangs occupy a key position in the global imaginary of violence, widely perceived and represented as primary sources of brutality and insecurity. This can be related to the fact that they are one of a small number of truly global phenomena, found in almost every society across both time and space. At the same time, however, as almost 100 years of gang research have highlighted, the phenomenon can vary significantly in form, dynamics, and consequences. While there have been many insightful studies of gangs, the overwhelming majority have focused on a single group or location, and we still lack a proper sense of what kinds of gang dynamics might be general, and which ones are specific to particular times and places. The GANGS project will develop a systematic comparative investigation of global gang dynamics, to better understand why they emerge, how they evolve over time, whether they are associated with particular urban configurations, how and why individuals join gangs, and what impact this has on their potential futures. It will draw on original ethnographic research carried out in multiple locations, adopting an explicitly tripartite focus on “Gangs”, “Gangsters”, and “Ganglands” in order to better explore the interplay between group, individual, and contextual factors. The first will consider the organisational dynamics of gangs, the second will focus on individual gang members and their trajectories before, during, and after their involvement in a gang, while the third will reflect on the contexts within which gangs emerge and evolve. Research will combine innovative collaborative ethnography in Nicaragua, South Africa, and France, a ground-breaking comparison of 35 individual gang member life histories from across Africa, Asia, Europe, North and South America, and unique joint ethnographic investigations into the political economy of three gang-affected cities in Nicaragua, France, and South Africa.

2 498 079 €

Start date: 2019-01-01, End date: 2023-12-31

The horizon is the line that seems to separate earth from sky, the line that divides all visible categories into two categories: those that intersect the earth’s surface and those that do not. The horizon is key to the experience of space; it defines our perspective on the visible world. The GLOBAL HORIZONS project will investigate the historical meanings and functions of the horizon in visual and intellectual cultures of the pre-Modern world on a global scale. Examining how pre-Modern cultures conceived of the horizon opens a crucial line of inquiry into understanding the many different ways in which humans have conceived of the relationship between an invisible cosmos and the visible world. Non-western art history is rarely taught at European institutions although countless important works of Non-Western art are kept in museum collections all across Europe. Including non-western concepts of pictorial space is key to the project, however, for Eurocentric models of art history have generally privileged the rise of the linear perspective. This framing has limited our understanding of the horizon’s complex rhetorical, visual and epistemological roles. The project’s specific question connects a variety of objects and epistemological categories, such as panel painting, manuscript illumination, profane und religious objects, cartography, travel accounts, and cosmological treaties. The applied methodological approaches will range from art history, visual studies and cultural anthropology. They will also draw upon interdisciplinary expertise, such as technologies of art production, history of science and philosophy. The project thus makes an important contribution to global art history, a highly innovative area in which only very few pre-modern topics have been addressed. It is the ultimate goal of GLOBAL HORIZONS is to suggest a new history of representation in Western medieval art.

1 904 188 €

Start date: 2018-09-01, End date: 2023-08-31

Unprecedented urbanization is threatening landscape diversity, bringing along new social and environmental problems. Standardized business centers, single family residential areas and shopping malls displace highly productive agricultural land, while the culture and lifestyles of local communities become absorbed into the sphere of globalization. This dramatic uniformisation is nurtured by the ever increasing global human migration. People are losing their sense of place and their motivation to initiate change. Uniformed international landscapes start dominating peri-urban areas. The result is a tremendous increase in fragility of these new landscapes of the twenty-first century, calling for an active and creative landscape shaping process to secure the long-term provision of critical ecosystem services. Up until now, however, models and tools developed in land system science have not caught up with the needs to understand and ultimately foster humans’ capacities to shape their landscapes. This project will contribute to a next generation of tools and methods to foster the development of resilient landscapes. I suggest linking design and probabilistic modeling in a collaborative landscape development tool to enable the transformation of spaces into places. This unconventional approach is necessary to deal with the probabilistic nature of landscapes. Landscapes can only be defined by including the observer – a concept severally neglected in today’s research efforts. Anchored in four peri-urban case studies, the interdisciplinary experimental and modeling work will have impact far beyond predicting transformation pathways of peri-urban landscapes under increased globalization. The resulting methods and tool will redefine the status quo of current geodesign tools, promote novel ways of deliberative decision-making and governance, and ultimately support humans to intentionally transform peri-urban landscapes.

1 498 106 €

Start date: 2018-06-01, End date: 2023-05-31

The goal of the proposed project is to create a universal (AKSZ type) topological field theory with values in graph complexes, capturing the rational homotopy types of manifolds, configuration and embedding spaces. If successful, such a theory will unite certain areas of mathematical physics, topology, homological algebra and algebraic geometry. More concretely, from the physical viewpoint it would give a precise topological interpretation of a class of well studied topological field theories, as opposed to the current state of the art, in which these theories are defined by giving formulae without guarantees on the non-triviality of the produced invariants. From the topological viewpoint such a theory will provide new tools to study much sought after objects like configuration and embedding spaces, and tentatively also diffeomorphism groups, through small combinatorial models given by Feynman diagrams. In particular, this will unite and extend existing graphical models of configuration and embedding spaces due to Kontsevich, Lambrechts, Volic, Arone, Turchin and others. From the homological algebra viewpoint a field theory as above provides a wealth of additional algebraic structures on the graph complexes, which are some of the most central and most mysterious objects in the field. Such algebraic structures are expected to yield constraints on the graph cohomology, as well as ways to construct series of previously unknown classes.

1 162 500 €

Start date: 2016-07-01, End date: 2021-06-30

Substantial advances in cosmology over the past decades have firmly established the standard model of cosmology. However, the physical nature of the early Universe and dark energy (or inflationary cosmology) remains poorly understood. To resolve these issues, a large number of galaxy surveys are planned to measure millions of galaxies in the sky, promising precision measurements of galaxy clustering with enormous statistical power. Despite these advances in observation, the standard theoretical description of galaxy clustering is based on the Newtonian description, inadequate for measuring the relativistic effects from the early Universe and the deviations of modified gravity from general relativity. In recent years, the applicant, for the first time, developed the linear-order general relativistic description of galaxy clustering and showed that the relativistic effect in galaxy clustering is already measurable at a few-sigma level in current surveys like the Sloan survey and significant detections (>10 sigma) are possible in upcoming surveys. This research proposal will aim to use the subtle relativistic effect in galaxy clustering to develop novel probes of inflationary cosmology. In particular, the applicant will 1) formulate the higher-order relativistic description of galaxy clustering, an essential tool for computing the bispectrum, and 2) investigate the unique relativistic signatures (linear-order and higher-order) in galaxy clustering from the early Universe and dark energy to develop novel probes of isolating those signatures and to quantify their detectabilities in future galaxy surveys. Biases in cosmological parameter estimation, if the standard Newtonian description is used, will be quantified. A comprehensive understanding of inflationary cosmology will have far-reaching consequences, shedding light on new physics beyond the standard model.

1 991 721 €

Start date: 2016-03-01, End date: 2021-02-28

Hydrogen bonds are ubiquitous and fundamental in nature, underpinning the behavior of systems as different as water, proteins and polymers. Much of this flexibility derives from their propensity to form complex topological networks, which can be strong enough to hold Kevlar together, or sufficiently labile to enable reversible structural transitions in allosteric proteins. Simulations must treat the quantum nature of both electrons and protons to describe accurately the microscopic structure of H-bonded materials, but this wealth of data does not necessarily translate into deep physical understanding. Even the structure of a compound as essential as water is still the subject of intense debate, despite extensive investigations. Identifying recurring bonding patterns is essential to comprehend and manipulate the structural and dynamical properties of H-bonded systems. Our objective is to develop and apply machine-learning techniques to atomistic simulations, and identify the design principles that govern the structure and properties of H-bonded compounds. Our strategy rests on three efforts: (1) recognition of recurring structural motifs with probabilistic data analysis; (2) coarse-grained mapping of the energetically accessible structural landscape by non-linear dimensionality reduction techniques; (3) acceleration of configuration sampling using these data-driven collective variables. Identifying motifs and order parameters will be crucial to interpret simulations and experiments of growing complexity, and will enable computational design of H-bond networks. We will focus first on two objectives. (1) Rationalizing the structure of crystalline, amorphous and liquid water across its phase diagram, from ambient to astrophysical conditions, and its response to solutes, interfaces or confinement. (2) Enabling efficient simulation and structural design of polymers and proteins in non-biological contexts, targeting biomimetic materials and organic/inorganic interfaces.

1 500 000 €

Start date: 2016-05-01, End date: 2021-04-30

Over the past two decades researchers have been working to create synthetic small-scale machines ranging from molecular entities or miniaturized structures, to more complex assemblies of micro- and nanomaterials. These machines are able to navigate in complex environments by harvesting fuel from the surrounding media or from external power sources. One of the most sought-after applications for these miniaturized machines is to perform minimally invasive interventions, in which these devices will ultimately reduce risk, cost, and discomfort compared to conventional interventions. This has driven researchers to produce a myriad of small-scale robots loaded with therapeutic cargo. While recent research has demonstrated the potential of these devices in animal models, a number of challenges remain in moving small-scale robots into the operating theatre. Here, we propose highly integrated nanorobots capable of realizing several functions on-demand by capitalizing on recent developments in small-scale robotics, multiferroics, supramolecular chemistry, and gated materials. These nanorobots will integrate a porous inorganic active chassis made of a piezoelectric or a magnetoelectric multiferroic that will host therapeutic agents, with redox or electroresponsive supramolecular gates that will control the release of payloads. We will demonstrate for the first time that redox- and electroresponsive supramolecular machinery grafted onto the surface of piezoelectric or multiferroic platforms can be remotely controlled by means of a piezoelectrochemical potential triggered by acoustic and magnetic fields. The ultimate goal of this research consists of creating smart multifunctional nanorobots, which will act on affected sites of the central nervous system by delivering therapeutic agents and electrostimulating the rewiring of neural circuitry.

1 998 720 €

Start date: 2018-09-01, End date: 2023-08-31

Severe spinal cord injury leads to a range of disabilities, including permanent motor impairments that seriously diminish the patients’ quality of life. In the framework of an ERC Starting Grant, my team and I developed a pragmatic therapy that restored supraspinal control of leg movement after complete paralysis in rats. However, the mechanisms underlying the effects of this intervention remain unknown. This fundamental knowledge is pivotal to operate a disruptive conversion from our empirical approach to an evidence-based strategy with clinical perspectives. Our therapy, termed neuroprosthetic rehabilitation, acts over two time windows. Immediately, electrical and chemical spinal cord stimulations mediate motor control of the paralysed hindlimbs. In the long term, will-powered training regimens enabled by electrochemical stimulation and robotic assistance promote neuroplasticity of residual connections—an extensive rewiring that reestablishes voluntary movement. Here, we propose to identify the circuit-level remodelling, computational principles, and molecular cues that govern the immediate and long-term recovery of motor functions. To address this knowledge gap, we will use our unique neuroprosthetic platform and next-generation experimental techniques for longitudinal assessment of neuroplasticity and function in freely behaving mice. These techniques combine optogenetics, circuit-level inactivation techniques, unconstrained chronic calcium imaging, virus-mediated tract-tracing and genetic manipulations. Our strategy consists of deploying a judicious association of these experimental techniques to establish causality between the reorganisation of the motor circuitry and functional recovery. This project will fertilize frontier research with new knowledge and ideas, ultimately accelerating clinical implementation of safer and more efficacious therapies to improve the quality of life for spinal cord injured individuals.

1 998 715 €

Start date: 2016-07-01, End date: 2021-06-30

The overall aim of the here described projects is to learn fundamental characteristics of cellular organization and compartmentalization, in particular the role of the lipid membrane, and to exploit this knowledge for engineering minimal cells with a great impact in the context of synthetic biology and also for pharmaceutical and medical applications. The first major objective aims at combining natural cell membranes with synthetic membranes to form defined hybrid systems with the size of cells or cell organelles. This approach has the intriguing advantage that the membrane receptors or channels are reconstituted in the hybrid cell and remain functional. In consequence, signaling pathways of a cell can be mimicked and therefore, the vesicles can be addressed similar to a cell or can serve as cell-free sensor. The second major objective addresses the challenge to build multi-compartment systems. In a defined number and formulation, smaller compartments are enclosed in a larger vesicle and carry other constituents than the lumen of the larger host vesicles (catalysts or enzymes, respectively; DNA; buffer systems; other active biomolecules). With the acquired fundamental knowledge on membrane permeability and fusion, multi-step reactions can be conducted, where several compartments are involved, just like in a living cell. The key methods to address these challenges are based on lab-on-chip technology that provide the unique potential to systematically investigate membrane properties by allowing precise formation, positioning, manipulation and analysis of the membranes; together with many more advantages such as the fast and controlled fluid supply, the possibility of tailoring the chemical surface patterns and surface topology and the application of electrical fields. Microfluidic platform will allow going far beyond the existing methods in membrane research, so that controlled bottom-up formation of simple to more and more complex systems becomes possible.

1 971 250 €

Start date: 2016-07-01, End date: 2021-06-30

Studying host-pathogen interactions by focusing on the interaction of a single pathogen with the host has defined our understanding of these events and the insights gained form the basis for the therapeutic and vaccination strategies we use today. However, people become infected with multiple pathogens throughout their lifetime, at times even simultaneously. Still, it is largely unknown how the immune response to one pathogen alters the body’s ability to respond to a second infectious agent or the susceptibility to autoimmunity or cancer. This project will address this question by focusing on infection-induced changes in regulatory T cells (Tregs) as they may lead to biased suppression and changes in the nature of subsequent immune responses. Our efforts will focus on two areas: In a first part, we will use single cell RNA-Seq to address how infections shape the Treg compartment by defining the specialized Treg subsets generated during polarized infectious settings and analyzing how they interact with effector T cells. Based on the depth of information we expect to obtain from this approach, we envisage finding thus far unappreciated interactions and functions of Tregs in the course of an immune response. The second part will investigate how an altered Treg compartment, either through genetic modifications or infection-induced, affects disease susceptibility. In this context, we will also address stability and persistence of pathogen-induced changes in the Treg compartment. Collectively the proposed experiments will allow us to start addressing how preceding infections affect disease susceptibility. Deciphering how infection history shapes the Treg compartment and how this affects susceptibility to future challenges will lay the groundwork for addressing this question more broadly in the future and as such will likely have a transformative impact on the field.

1 499 755 €

Start date: 2016-06-01, End date: 2021-05-31

Plant receptor kinases are major pattern recognition receptors (PRRs) that function as part of dynamic multimeric complexes to perceive pathogen-associated molecular patterns or host-derived damage-associated molecular patterns at the plasma membrane (PM). Our long-term objective is to decipher the molecular basis of plant innate immunity and to understand how plant receptor kinases work. Our recent findings point to an important role of endogenous peptides in the regulation of plant innate immune signaling. The main aim of this proposal is to understand how these endogenous peptides and their corresponding receptors regulate plant innate immune signaling. The central hypotheses of this research are that: (i) a subset of plant endogenous peptides are perceived by receptor kinases to fine-tune dynamically plant innate immune signaling, and thus act as ‘phytocytokines’; (ii) these phytocytokines and their receptors regulate the formation of active immune-signaling nanoclusters at the PM; and (iii) phytocytokine receptors participate in the sensory continuum represented by the plant PM and the cell wall to respond dynamically to environmental challenges. We will pursue the following specific objectives: (1) decipher the regulation, function, and perception of RALF peptides by malectin-like receptor kinases during immunity; (2) elucidate the formation, composition, and function of PM immune receptor nanoclusters; (3) reveal the function of the receptor kinase MIK2 and its ligand(s) in immunity. Through a balanced combination of straight-forward and high risk/high gain biochemical, biophysical, bioimaging, and genetics approaches, this project will provide groundbreaking insights into the molecular mechanisms underlying the establishment and regulation of plant innate immune signaling, but also into the general mechanisms that control plant receptor kinase functions and by which the myriad endogenous peptides encoded by plant genomes control environmental sensing.

1 999 999 €

Start date: 2018-06-01, End date: 2023-05-31

Energy efficiency offers a vast and low-cost resource to address future energy demand while reducing carbon dioxide emissions. The unique properties of III-Nitride semiconductors make them the ideal material for future energy challenges. Their outstanding optical properties are revolutionizing the world with efficient LED light bulbs. Even greater impact is anticipated for power electronics. The much larger Baliga’s figure of merit of GaN compared to SiC and Si enables drastically more efficient power switches, which are at the heart of any energy generation/management system. However, current III-Nitride device performance is far from the fundamental materials capabilities, and severe thermal management and reliability limitations hinder their full potential for energy-efficiency. The In-Need proposes a unique approach to address concurrently all current challenges based on advanced nanostructures designed to optimally exploit the superior properties of the new bulk GaN materials. Nanostructuring distinct regions of the device will allow a precise control over their intrinsic characteristics. To address reliability issues and yield unprecedented device performance, these nanostructures will be combined to the excellent properties of bulk GaN. This will open opportunities for new vertical devices, enabling smaller structures with larger voltages and higher efficiencies. Efficient thermal management will be achieved with ultra-near junction cooling. Nano/micro-channels filled with high thermal conductivity materials or coolants will be embedded inside the device. We believe our judicious nano-scale design of new high-performing materials will result in state-of-the-art devices, leading to a large-scale impact in energy efficiency. The miniaturization and large power density enabled by our approach will allow future integration of power devices into single power microchips. This will revolutionize energy use much like Silicon microchips did for information processing.

1 750 000 €

Start date: 2016-02-01, End date: 2021-01-31