ERC FUNDED PROJECTS

I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.

2 311 696 €

Start date: 2017-09-01, End date: 2022-08-31

This project presents a new concept for the detection, diagnosis and monitoring of cancer biomarker patterns in point-of-care. The device under development will make use of the selectivity of the plastic antibodies as sensing materials and the interference they will play on the normal operation of a photovoltaic cell. Plastic antibodies will be designed by surface imprinting procedures. Self-assembled monolayer and molecular imprinting techniques will be merged in this process because they allow the self-assembly of nanostructured materials on a “bottom-up” nanofabrication approach. A dye-sensitized solar cell will be used as photovoltaic cell. It includes a liquid interface in the cell circuit, which allows the introduction of the sample (also in liquid phase) without disturbing the normal cell operation. Furthermore, it works well with rather low cost materials and requires mild and easy processing conditions. The cell will be equipped with plasmonic structures to enhance light absorption and cell efficiency. The device under development will be easily operated by any clinician or patient. It will require ambient light and a regular multimeter. Eye detection will be also tried out.

998 584 €

Start date: 2013-02-01, End date: 2018-01-31

Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.

2 318 636 €

Start date: 2010-07-01, End date: 2015-12-31

When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.

1 969 750 €

Start date: 2019-02-01, End date: 2024-01-31

What is the origin of cosmic rays, what are the dominant acceleration mechanisms in relativistic shocks, how do cosmic rays self-consistently influence the shock dynamics, how are relativistic collisionless shocks formed are longstanding scientific questions, closely tied to extreme plasma physics processes, and where a close interplay between the micro-instabilities and the global dynamics is critical. Relativistic shocks are closely connected with the propagation of intense streams of particles pervasive in many astrophysical scenarios. The possibility of exciting shocks in the laboratory will also be available very soon with multi-PW lasers or intense relativistic particle beams. Computational modeling is now established as a prominent research tool, by enabling the fully kinetic modeling of these systems for the first time. With the fast paced developments in high performance computing, the time is ripe for a focused research programme on simulation-based studies of relativistic shocks. This proposal therefore focuses on using self-consistent ab initio massively parallel simulations to study the physics of relativistic shocks, bridging the gap between the multidimensional microphysics of shock onset, formation, and propagation and the global system dynamics. Particular focus will be given to the shock acceleration mechanisms and the radiation signatures of the various physical processes, with the goal of solving some of the central questions in plasma/relativistic phenomena in astrophysics and in the laboratory, and opening new avenues between theoretical/massive computational studies, laboratory experiments and astrophysical observations.

1 588 800 €

Start date: 2011-06-01, End date: 2016-07-31

"Children learn any language that they grow up with, adapting to any of the ca. 7000 languages of the world, no matter how divergent or complex their structures are. What cognitive processes make this extreme flexibility possible? This is one of the most burning questions in cognitive science and the ACQDIV project aims at answering it by testing and refining the following leading hypothesis: Language acquisition is flexible and adaptive to any kind of language because it relies on a small set of universal cognitive processes that variably target different structures at different times during acquisition in every language. The project aims at establishing the precise set of processes and at determining the conditions of variation across maximally diverse languages. This project focuses on three processes: (i) distributional learning, (ii) generalization-based learning and (iii) interaction-based learning. To investigate these processes I will work with a sample of five clusters of languages including longitudinal data of two languages each. The clusters were determined by a clustering algorithm seeking the structurally most divergent languages in a typological database. The languages are: Cluster 1: Slavey and Cree, Cluster 2: Indonesian and Yucatec, Cluster 3: Inuktitut and Chintang, Cluster 4: Sesotho and Russian, Cluster 5: Japanese and Turkish. For all languages, corpora are available, except for Slavey where fieldwork is planned. The leading hypothesis will be tested against the acquisition of aspect and negation in each language of the sample and also against the two structures in each language that are most salient and challenging in them (e. g. complex morphology in Chintang). The acquisition processes also depend on statistical patterns in the input children receive. I will examine these patterns across the sample with respect to repetitiveness effects, applying data-mining methods and systematically comparing child-directed and child-surrounding speech."

1 998 438 €

Start date: 2014-09-01, End date: 2019-08-31

The brain evolves, develops, and operates in the context of animal movements. As a consequence, fundamental brain functions such as spatial perception and motor control critically depend on the precise knowledge of the ongoing body motion. An accurate internal estimate of self-movement is thought to emerge from sensorimotor integration; nonetheless, which circuits perform this internal estimation, and exactly how motor-sensory coordination is implemented within these circuits are basic questions that remain to be poorly understood. There is growing evidence suggesting that, during locomotion, motor-related and visual signals interact at early stages of visual processing. In mammals, however, it is not clear what the function of this interaction is. Recently, we have shown that a population of Drosophila optic-flow processing neurons —neurons that are sensitive to self-generated visual flow, receives convergent visual and walking-related signals to form a faithful representation of the fly’s walking movements. Leveraging from these results, and combining quantitative analysis of behavior with physiology, optogenetics, and modelling, we propose to investigate circuit mechanisms of self-movement estimation during walking. We will:1) use cell specific manipulations to identify what cells are necessary to generate the motor-related activity in the population of visual neurons, 2) record from the identified neurons and correlate their activity with specific locomotor parameters, and 3) perturb the activity of different cell-types within the identified circuits to test their role in the dynamics of the visual neurons, and on the fly’s walking behavior. These experiments will establish unprecedented causal relationships among neural activity, the formation of an internal representation, and locomotor control. The identified sensorimotor principles will establish a framework that can be tested in other scenarios or animal systems with implications both in health and disease.

1 500 000 €

Start date: 2017-11-01, End date: 2022-10-31

Hail and storm damages represent the most often occurring cases for building insurance companies. Currently, the damage is estimated by an insurance expert, visiting the damaged building and drafting a report. Researchers at the Computer Vision Lab at ETH Zurich joined forces with business and sales people, spinning out the company Casalva, to strongly reduce such costs via automated image analysis. The idea is that the insurers’ clients upload photos of the damages, which will then be analyzed automatically by a computer. This involves computer vision technologies – grounded in the ERC project VarCity – to recognize the damaged building structures and to analyze the corresponding textures as to assess the extent of the damage and the estimated costs for its repair. Cutting costs is not the only consideration, as the fast assessment of damages improves customer satisfaction and prevents the occurrence of additional damages because of a delayed repair (like water leaking before repair). Such follow-on damages are estimated to be 20% of overall costs on average and are therefore far from negligible. Guaranteeing a short term response currently is a major issue, as a single storm may affect thousands of buildings. Processing times tend to stretch out due to the peak in cases following such extreme weather events. Over half of hail storm damage cases concern facade structures. The VarCity project produced methods to automatically parse facades into such structures, and to select the best way to describe their textures. These will be refined to optimally deal with the application area. The remaining technical developments and risk mitigations will be funded through other means (a Swiss project that has already been submitted), while this Proof-of-Concept project will focus on equally important aspects like market analysis, development of a corporate identity and graphical house style for the Casalva spin-off, that has been created but should now get market introduction.

143 750 €

Start date: 2017-09-01, End date: 2018-08-31

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

"Contemporary database query languages are ultimately founded on logic and feature an additive operation – usually a form of (multi)set union or disjunction – that is asymmetric in that additions or updates do not always have an inverse. This asymmetry puts a greater part of the machinery of abstract algebra for equation solving outside the reach of databases. However, such equation solving would be a key functionality that problems such as query equivalence testing and data integration could be reduced to: In the current scenario of the presence of an asymmetric additive operation they are undecidable. Moreover, query languages with a symmetric additive operation (i.e., which has an inverse and is thus based on ring theory) would open up databases for a large range of new scientific and mathematical applications. The goal of the proposed project is to reinvent database management systems with a foundation in abstract algebra and specifically in ring theory. The presence of an additive inverse allows to cleanly define differences between queries. This gives rise to a database analog of differential calculus that leads to radically new incremental and adaptive query evaluation algorithms that substantially outperform the state of the art techniques. These algorithms enable a new class of systems which I call Dynamic Data Management Systems. Such systems can maintain continuously fresh query views at extremely high update rates and have important applications in interactive Large-scale Data Analysis. There is a natural connection between differences and updates, motivating the group theoretic study of updates that will lead to better ways of creating out-of-core data processing algorithms for new storage devices. Basing queries on ring theory leads to a new class of systems, Algebraic Data Management Systems, which herald a convergence of database systems and computer algebra systems."

1 480 548 €

Start date: 2012-01-01, End date: 2016-12-31

Europe sits uncomfortably on the idea that there are no political and cultural alternatives credible enough to respond to the current uneasiness or malaise caused by both a world that is more and more non-European and a Europe that increasingly questions what is European about itself. This project will develop a new grounded theoretical paradigm for contemporary Europe based on two key ideas: the understanding of the world by far exceeds the European understanding of the world; social, political and institutional transformation in Europe may benefit from innovations taking place in regions and countries with which Europe is increasingly interdependent. I will pursue this objective focusing on four main interconnected topics: democratizing democracy, intercultural constitutionalism, the other economy, human rights (right to health in particular). In a sense that the European challenges are unique but, in one way or another, are being experienced in different corners of the world. The novelty resides in bringing new ideas and experiences into the European conversation, show their relevance to our current uncertainties and aspirations and thereby contribute to face them with new intellectual and political resources. The usefulness and relevance of non-European conceptions and experiences un-thinking the conventional knowledge through two epistemological devices I have developed: the ecology of knowledges and intercultural translation. By resorting to them I will show that there are alternatives but they cannot be made credible and powerful if we go on relying on the modes of theoretical and political thinking that have dominated so far. In other words, the claim put forward by and worked through this project is that in Europe we don’t need alternatives but rather an alternative thinking of alternatives.

2 423 140 €

Start date: 2011-07-01, End date: 2016-12-31

Mitochondria are often referred to as the “power houses” of eukaryotic cells. All eukaryotes were thought to have mitochondria of some form until 2016, when the first eukaryote thriving without mitochondria was discovered by our laboratory – a flagellate Monocercomonoides. Understanding cellular functions of these cells, which represent a new functional type of eukaryotes, and understanding the circumstances of the unique event of mitochondrial loss are motivations for this proposal. The first objective focuses on the cell physiology. We will perform a metabolomic study revealing major metabolic pathways and concentrate further on elucidating its unique system of iron-sulphur cluster assembly. In the second objective, we will investigate in details the unique case of mitochondrial loss. We will examine two additional potentially amitochondriate lineages by means of genomics and transcriptomics, conduct experiments simulating the moments of mitochondrial loss and try to induce the mitochondrial loss in vitro by knocking out or down genes for mitochondrial biogenesis. We have chosen Giardia intestinalis and Entamoeba histolytica as models for the latter experiments, because their mitochondria are already reduced to minimalistic “mitosomes” and because some genetic tools are already available for them. Successful mitochondrial knock-outs would enable us to study mitochondrial loss in ‘real time’ and in vivo. In the third objective, we will focus on transforming Monocercomonoides into a tractable laboratory model by developing methods of axenic cultivation and genetic manipulation. This will open new possibilities in the studies of this organism and create a cell culture representing an amitochondriate model for cell biological studies enabling the dissection of mitochondrial effects from those of other compartments. The team is composed of the laboratory of PI and eight invited experts and we hope it has the ability to address these challenging questions.

1 935 500 €

Start date: 2018-05-01, End date: 2023-04-30

The project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits. In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application. Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.

2 497 200 €

Start date: 2016-01-01, End date: 2020-12-31

Calcium-activated chloride channels (CaCCs) play key roles in a range of physiological processes such as the control of membrane excitability, photoreception and epithelial secretion. Although the importance of these channels has been recognized for more than 30 years their molecular identity remained obscure. The recent discovery of two protein families encoding for CaCCs, Anoctamins and Bestrophins, was a scientific breakthrough that has provided first insight into two novel ion channel architectures. Within this proposal we aim to determine the first high resolution structures of members of both families and study their functional behavior by an interdisciplinary approach combining biochemistry, X-ray crystallography and electrophysiology. The structural investigation of eukaryotic membrane proteins is extremely challenging and will require us to investigate large numbers of candidates to single out family members with superior biochemical properties. During the last year we have made large progress in this direction. By screening numerous eukaryotic Anoctamins and prokaryotic Bestrophins we have identified well-behaved proteins for both families, which were successfully scaled-up and purified. Additional family members will be identified within the course of the project. For these stable proteins we plan to grow crystals diffracting to high resolution and to proceed with structure determination. With first structural information in hand we will perform detailed functional studies using electrophysiology and complementary biophysical techniques to gain mechanistic insight into ion permeation and gating. As the pharmacology of both families is still in its infancy we will in later stages also engage in the identification and characterization of inhibitors and activators of Anoctamins and Bestrophins to open up a field that may ultimately lead to the discovery of novel therapeutic strategies targeting calcium-activated chloride channels.

2 176 000 €

Start date: 2014-02-01, End date: 2020-01-31

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

The evolutionary pressures exerted by viruses on their host cells constitute a major force that drives the evolution of cellular antiviral mechanisms. The proposed research is motivated by our interest in the roles of protein-RNA interactions in both prokaryotic and eukaryotic antiviral pathways and will proceed in two directions. The first project stems from our current work on the CRISPR pathway, a recently discovered RNA-guided adaptive defense mechanism in bacteria and archaea that silences mobile genetic elements such as viruses (bacteriophages) and plasmids. CRISPR systems rely on short RNAs (crRNAs) that associate with CRISPR-associated (Cas) proteins and function as sequence-specific guides in the detection and destruction of invading nucleic acids. To obtain molecular insights into the mechanisms of crRNA-guided interference, we will pursue structural and functional studies of DNA-targeting ribonuceoprotein complexes from type II and III CRISPR systems. Our work will shed light on the function of these systems in microbial pathogenesis and provide a framework for the informed engineering of RNA-guided gene targeting technologies. The second proposed research direction centres on RNA-targeting antiviral strategies employed by the human innate immune system. Here, our work will focus on structural studies of major interferon-induced effector proteins, initially examining the allosteric activation mechanism of RNase L and subsequently focusing on other antiviral nucleases and RNA helicases, as well as mechanisms by which RNA viruses evade the innate immune response of the host. In our investigations, we plan to approach these questions using an integrated strategy combining structural biology, biochemistry and biophysics with cell-based functional studies. Together, our studies will provide fundamental molecular insights into RNA-centred antiviral mechanisms and their impact on human health and disease.

1 467 180 €

Start date: 2013-11-01, End date: 2018-10-31

The description of high pressure phases or polymorphism of molecular solids represents a significant scientific challenge both for experiment and theory. Theoretical methods that are currently used struggle to describe the tiny energy differences between different phases. It is the aim of this project to develop a scheme that would allow accurate and reliable predictions of the binding energies of molecular solids and of the energy differences between different phases. To reach the required accuracy, we will combine the coupled cluster approach, widely used for reference quality calculations for molecules, with the random phase approximation (RPA) within periodic boundary conditions. As I have recently shown, RPA-based approaches are already some of the most accurate and practically usable methods for the description of extended systems. However, reliability is not only a question of accuracy. Reliable data need to be precise, that is, converged with the numerical parameters so that they are reproducible by other researchers. Reproducibility is already a growing concern in the field. It is likely to become a considerable issue for highly accurate methods as the calculated energies have a stronger dependence on the simulation parameters such as the basis set size. Two main approaches will be explored to assure precision. First, we will develop the so-called asymptotic correction scheme to speed-up the convergence of the correlation energies with the basis set size. Second, we will directly compare the lattice energies from periodic and finite cluster based calculations. Both should yield identical answers, but if and how the agreement can be reached for general system is currently far from being understood for methods such as coupled cluster. Reliable data will allow us to answer some of the open questions regarding the stability of polymorphs and high pressure phases, such as the possibility of existence of high pressure ionic phases of water and ammonia.

924 375 €

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

ARTIVISM aims at exploring new artistic forms of political expression under difficult, precarious and/or oppressive conditions. It asks how social actors create belonging and multiple forms of resistance when they use art in activism or activism in art. What kind of alliances do these two forms of social practices generate in super-diverse places, in times of crisis and in precarious situations? Thus, ARTIVISM seeks to understand how social actors engage artistically in order to bring about social, economic and political change. Going beyond former research in urban and migration studies, and beyond the anthropology of art, ARTIVISM focuses on a broad range of artistic tools, styles and means of expression, namely festive events and parades, cartoons and comics and street art. By articulating performance studies, street anthropology and the sociology of celebration with migration and diversity studies, the project challenges former concepts, which took stable social groups for granted and reified them with ethnic lenses. The applied methodology considerably renews the field by bringing together event-, actor- and condition-centred approaches and a multi-sensory framework. Besides its multidisciplinary design, the ground-breaking nature of ARTIVISM lies in the application of the core concepts of performativity and liminality, as well as in an examination of the way to advance and refine these concepts and to create new analytical tools to respond to recent social phenomena. We have developed and tested innovative methods that respond to a postmodern type of fluid and temporary social action: audio-visual ethnography, urban event ethnography, street ethnography, field-crossing, and sensory ethnography (apprenticeship). Therefore, ARTIVISM develops new methods and theories in order to introduce a multi-faceted trans-disciplinary approach to the study of an emerging field of social transformations that is of challenging significance to the social sciences.

1 999 287 €

Start date: 2016-09-01, End date: 2021-08-31

New generations of devices for tissue engineering (TE) should rationalize better the physical and biochemical cues operating in tandem during native regeneration, in particular at the scale/organizational-level of the stem cell niche. The understanding and the deconstruction of these factors (e.g. multiple cell types exchanging both paracrine and direct signals, structural and chemical arrangement of the extra-cellular matrix, mechanical signals…) should be then incorporated into the design of truly biomimetic biomaterials. ATLAS proposes rather unique toolboxes combining smart biomaterials and cells for the ground-breaking advances of engineering fully time-self-regulated complex 2D and 3D devices, able to adjust the cascade of processes leading to faster high-quality new tissue formation with minimum pre-processing of cells. Versatile biomaterials based on marine-origin macromolecules will be used, namely in the supramolecular assembly of instructive multilayers as nanostratified building-blocks for engineer such structures. The backbone of these biopolymers will be equipped with a variety of (bio)chemical elements permitting: post-processing chemistry and micro-patterning, specific/non-specific cell attachment, and cell-controlled degradation. Aiming at being applied in bone TE, ATLAS will integrate cells from different units of tissue physiology, namely bone and hematopoietic basic elements and consider the interactions between the immune and skeletal systems. These ingredients will permit to architect innovative films with high-level dialogue control with cells, but in particular sophisticated quasi-closed 3D capsules able to compartmentalise such components in a “globe-like” organization, providing local and long-range order for in vitro microtissue development and function. Such hybrid devices could be used in more generalised front-edge applications, including as disease models for drug discovery or test new therapies in vitro.

2 498 988 €

Start date: 2015-12-01, End date: 2020-11-30

The attoclock is a powerful, new, and unconventional tool to study fundamental attosecond dynamics on an atomic scale. We established its potential by using the first attoclock to measure the tunneling delay time in laser-induced ionization of helium and argon atoms, with surprising results. Building on these first proof-of-principle measurements, I propose to amplify and expand this tool concept to explore the following key questions: How fast can light liberate electrons from a single atom, a single molecule, or a solid-state system? Related are more questions: How fast can an electron tunnel through a potential barrier? How fast is a multi-photon absorption process? How fast is single-photon photoemission? Many of these questions will undoubtedly spark more questions – revealing deeper and more detailed insights on the dynamics of some of the most fundamental and relevant optoelectronic processes. There are still many unknown and unexplored areas here. Theory has failed to offer definitive answers. Simulations based on the exact time-dependent Schrödinger equation have not been possible in most cases. Therefore one uses approximations and simpler models to capture the essential physics. Such semi-classical models potentially will help to understand attosecond energy and charge transport in larger molecular systems. Indeed the attoclock provides a unique tool to explore different semi-classical models. For example, the question of whether electron tunneling through an energetically forbidden region takes a finite time or is instantaneous has been subject to ongoing debate for the last sixty years. The tunnelling process, charge transfer, and energy transport all play key roles in electronics, energy conversion, chemical and biological reactions, and fundamental processes important for improved information, health, and energy technologies. We believe the attoclock can help refine and resolve key models for many of these important underlying attosecond processes.

2 319 796 €

Start date: 2013-03-01, End date: 2018-02-28

"The goal of the present proposal is to realize measurements of electronic dynamics in polyatomic molecules with attosecond temporal resolution (1 as = 10^-18s). We propose to study electronic rearrangements following photoexcitation, charge migration in a molecular chain induced by ionization and non-adiabatic multi-electron dynamics in an intense laser field. The grand question addressed by this research is the characterization of electron correlations which control the shape, properties and function of molecules. In all three proposed projects, a time-domain approach appears to be the most suitable since it reduces complex molecular dynamics to the purely electronic dynamics by exploiting the hierarchy of motional time scales. Experimentally, we propose to realize an innovative experimental setup. A few-cycle infrared (IR) pulse will be used to generate attosecond pulses in the extreme-ultraviolet (XUV) by high-harmonic generation. The IR pulse will be separated from the XUV by means of an innovative interferometer. Additionally, it will permit the introduction of a controlled attosecond delay between the two pulses. We propose to use the attosecond pulses as a tool to look inside individual IR- or UV-field cycles to better understand light-matter interactions. Time-resolved pump-probe experiments will be carried out on polyatomic molecules by detecting the energy and angular distribution of photoelectrons in a velocity-map imaging spectrometer. These experiments are expected to provide new insights into the dynamics of multi-electron systems along with new results for the validation and improvement of theoretical models. Multi-electron dynamics is indeed a very complex subject on its own and even more so in the presence of strong laser fields. The proposed experiments directly address theses challenges and are expected to provide new insights that will be beneficial to a wide range of scientific research areas."

1 999 992 €

Start date: 2012-09-01, End date: 2017-08-31

The formation of a functional patterned vascular network is essential for development, tissue growth and organ physiology. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms and diabetic retinopathy. Although blood flow is recognised as a stimulus for vascular patterning, very little is known about the molecular mechanisms that regulate endothelial cell behaviour in response to flow and promote vascular patterning. Recently, we uncovered that endothelial cells migrate extensively in the immature vascular network, and that endothelial cells polarise against the blood flow direction. Here, we put forward the hypothesis that vascular patterning is dependent on the polarisation and migration of endothelial cells against the flow direction, in a continuous flux of cells going from low-shear stress to high-shear stress regions. We will establish new reporter mouse lines to observe and manipulate endothelial polarity in vivo in order to investigate how polarisation and coordination of endothelial cells movements are orchestrated to generate vascular patterning. We will manipulate cell polarity using mouse models to understand the importance of cell polarisation in vascular patterning. Also, using a unique zebrafish line allowing analysis of endothelial cell polarity, we will perform a screen to identify novel regulators of vascular patterning. Finally, we will explore the hypothesis that defective flow-dependent endothelial polarisation underlies arteriovenous malformations using two genetic models. This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders.

1 618 750 €

Start date: 2016-09-01, End date: 2021-08-31

Pseudoscalar QCD axions and axion-like Particles (ALPs) are an excellent candidate for Dark Matter or can act as a mediator particle for Dark Matter. Since the discovery of the Higgs boson, we know that fundamental scalars exist and it is timely to explore the Axion/ALP parameter space more intensively. A look at the allowed axion/ALP parameter space makes it clear that these might exist at low mass (below few eV), as (part of) Dark Matter. Alternatively they might exist at higher mass, above roughly the MeV scale, potentially as a Dark Matter mediator particle. AxScale explores parts of these different mass regions, with complementary techniques but with one research team. Firstly, with RADES, it develops a novel concept for a filter-like cavity for the search of QCD axion Dark matter at a few tens of a micro-eV. Dark Matter Axions can be discovered by their resonant conversion in that cavity embedded in a strong magnetic field. The `classical axion window' has recently received much interest from cosmological model-building and I will implement a novel cavity concept that will allow to explore this Dark Matter parameter region. Secondly, AxScale searches for axions and ALPs using the NA62 detector at CERN's SPS. Especially the mass region above a few MeV can be efficiently searched by the use of a proton fixed-target facility. During nominal data taking NA62 investigates a Kaon beam. NA62 can also run in a mode in which its primary proton beam is fully dumped. With the resulting high interaction rate, the existence of weakly coupled particles can be efficiently probed. Thus, searches for ALPs from Kaon decays as well as from production in dumped protons with NA62 are foreseen in AxScale. More generally, NA62 can look for a plethora of `Dark Sector' particles with recorded and future data. With the AxScale program I aim at maximizing the reach of NA62 for these new physics models.

1 134 375 €

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

All levels of life entail cooperation and conflict. Genes cooperate to build up a functional genome, which can yet be undermined by selfish genetic elements. Humans and animals cooperate to build up societies, which can yet be subverted by cheats. There is a long-standing interest among biologists to comprehend the tug-of-war between cooperation and conflict. Recently, research on bacteria was successful in identifying key factors that can tip the balance in favour or against cooperation. Bacteria cooperate through the formation of protective biofilms, cell-to-cell communication, and the secretion of shareable public goods. However, the advantage of bacteria being fast replicating units, easily cultivatable in high numbers, is also their disadvantage: they are small and imperceptible, such that measures of cooperation typically rely on averaged responses across millions of cells. Thus, we still know very little about bacterial cooperation at the biological relevant scale: the individual cell level. Here, I present research using the secretion of public goods in the opportunistic human pathogen Pseudomonas aeruginosa, to tackle this issue. I will explore new dimensions of bacterial cooperation by asking whether bacteria engage in collective-decision making to find optimal group-level solutions; whether bacteria show division of labour to split up work efficiently; and whether bacteria can distinguish between trustworthy and cheating partners. The proposed research will make two significant contributions. First, it will reveal whether bacteria engage in complex forms of cooperation (collective decision-making, division of labour, partner recognition), which have traditionally been associated with higher organisms. Second, it will provide insights into the evolutionary stability of cooperation – key knowledge for designing therapies that interfere with virulence-inducing public goods in infections, and the design of stable public-good based remediation processes.

1 994 981 €

Start date: 2016-09-01, End date: 2021-08-31