ERC FUNDED PROJECTS

The overall goal of 14Constraint is to enhance the availability and use of radiocarbon data as constraints for process-based understanding of the age distribution of carbon in and respired by soils and ecosystems. Carbon enters ecosystems by a single process, photosynthesis. It returns by a range of processes that depend on plant allocation and turnover, the efficiency and rate of litter decomposition and the mechanisms stabilizing C in soils. Thus the age distribution of respired CO2 and the age of C residing in plants, litter and soils are diagnostic properties of ecosystems that provide key constraints for testing carbon cycle models. Radiocarbon, especially the transit of ‘bomb’ 14C created in the 1960s, is a powerful tool for tracing C exchange on decadal to centennial timescales. 14Constraint will assemble a global database of existing radiocarbon data (WP1) and demonstrate how they can constrain and test ecosystem carbon cycle models. WP2 will fill data gaps and add new data from sites in key biomes that have ancillary data sufficient to construct belowground C and 14C budgets. These detailed investigations will focus on the role of time lags caused in necromass and fine roots, as well as the dynamics of deep soil C. Spatial extrapolation beyond the WP2 sites will require sampling along global gradients designed to explore the relative roles of mineralogy, vegetation and climate on the age of C in and respired from soil (WP3). Products of this 14Constraint will include the first publicly available global synthesis of terrestrial 14C data, and will add over 5000 new measurements. This project is urgently needed before atmospheric 14C levels decline to below 1950 levels as expected in the next decade.

2 283 747 €

Start date: 2016-12-01, End date: 2021-11-30

Since its discovery, graphene has been indicated as a promising platform for quantum technologies (QT). The number of theoretical proposal dedicated to this vision has grown steadily, exploring a wide range of directions, ranging from spin and valley qubits, to topologically-protected states. The experimental confirmation of these ideas lagged so far significantly behind, mostly because of material quality problems. The quality of graphene-based devices has however improved dramatically in the past five years, thanks to the advent of the so-called van der Waals (vdW) heteostructures - artificial solids formed by mechanically stacking layers of different two dimensional (2D) materials, such as graphene, hexagonal boron nitride and transition metal dichalcogenides. These new advances open now finally the door to put several of those theoretical proposals to test. The goal of this project is to assess experimentally the potential of graphene-based heterostructures for QT applications. Specifically, I will push the development of an advanced technological platform for vdW heterostructures, which will allow to give quantitative answers to the following open questions: i) what are the relaxation and coherence times of spin and valley qubits in isotopically purified bilayer graphene (BLG); ii) what is the efficiency of a Cooper-pair splitter based on BLG; and iii) what are the characteristic energy scales of topologically protected quantum states engineered in graphene-based heterostructures. At the end of this project, I aim at being in the position of saying whether graphene is the horse-worth-betting-on predicted by theory, or whether it still hides surprises in terms of fundamental physics. The technological advancements developed in this project for integrating nanostructured layers into vdW heterostructures will reach even beyond this goal, opening the door to new research directions and possible applications.

1 806 250 €

Start date: 2019-09-01, End date: 2024-08-31

The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research. The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation. The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event. Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.

1 489 823 €

Start date: 2017-03-01, End date: 2022-02-28

The applicant will collaborate with Irish, European and U.S.-based colleagues to develop a sustainable biorefinery and bioenergy industry in Ireland and Europe. The focus of this ERC Starting Grant will be the application of classical microbiological, physiological and real-time polymerase chain reaction (PCR)-based assays, to qualitatively and quantitatively characterize microbial communities underpinning novel and innovative, low-temperature, anaerobic waste (and other biomass) conversion technologies, including municipal wastewater treatment and, demonstration- and full-scale biorefinery applications. Anaerobic digestion (AD) is a naturally-occurring process, which is widely applied for the conversion of waste to methane-containing biogas. Low-temperature (<20 degrees C) AD has been applied by the applicant as a cost-effective alternative to mesophilic (c. 35C) AD for the treatment of several waste categories. However, the microbiology of low-temperature AD is poorly understood. The applicant will work with microbial consortia isolated from anaerobic bioreactors, which have been operated for long-term experiments (>3.5 years), and include organic acid-oxidizing, hydrogen-producing syntrophic microbes and hydrogen-consuming methanogens. A major focus of the project will be the ecophysiology of psychrotolerant and psychrophilic methanogens already identified and cultivated by the applicant. The project will also investigate the role(s) of poorly-understood Crenarchaeota populations and homoacetogenic bacteria, in complex consortia. The host organization is a leading player in the microbiology of waste-to-energy applications. The applicant will train a team of scientists in all aspects of the microbiology and bioengineering of biomass conversion systems.

1 499 797 €

Start date: 2011-05-01, End date: 2016-04-30

My vision is to establish, within the framework of an ERC CoG, a multidisciplinary group which will work in concert towards pioneering the integration of novel 2-Dimensional nanomaterials with novel additive fabrication techniques to develop a unique class of energy storage devices. Batteries and supercapacitors are two very complementary types of energy storage devices. Batteries store much higher energy densities; supercapacitors, on the other hand, hold one tenth of the electricity per unit of volume or weight as compared to batteries but can achieve much higher power densities. Technology is currently striving to improve the power density of batteries and the energy density of supercapacitors. To do so it is imperative to develop new materials, chemistries and manufacturing strategies. 3D2DPrint aims to develop micro-energy devices (both supercapacitors and batteries), technologies particularly relevant in the context of the emergent industry of micro-electro-mechanical systems and constantly downsized electronics. We plan to use novel two-dimensional (2D) nanomaterials obtained by liquid-phase exfoliation. This method offers a new, economic and easy way to prepare ink of a variety of 2D systems, allowing to produce wide device performance window through elegant and simple constituent control at the point of fabrication. 3D2DPrint will use our expertise and know-how to allow development of advanced AM methods to integrate dissimilar nanomaterial blends and/or “hybrids” into fully embedded 3D printed energy storage devices, with the ultimate objective to realise a range of products that contain the above described nanomaterials subcomponent devices, electrical connections and traditional micro-fabricated subcomponents (if needed) ideally using a single tool.

2 499 942 €

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

This proposal brings together two fields in biology, namely the emerging field of phase-separated assemblies in cell biology and state-of-the-art cellular cryo-electron tomography, to advance our understanding on a fundamental, yet illusive, question: the molecular organization of the cytoplasm. Eukaryotes organize their biochemical reactions into functionally distinct compartments. Intriguingly, many, if not most, cellular compartments are not membrane enclosed. Rather, they assemble dynamically by phase separation, typically triggered upon a specific event. Despite significant progress on reconstituting such liquid-like assemblies in vitro, we lack information as to whether these compartments in vivo are indeed amorphous liquids, or whether they exhibit structural features such as gels or fibers. My recent work on sample preparation of cells for cryo-electron tomography, including cryo-focused ion beam thinning, guided by 3D correlative fluorescence microscopy, shows that we can now prepare site-specific ‘electron-transparent windows’ in suitable eukaryotic systems, which allow direct examination of structural features of cellular compartments in their cellular context. Here, we will use these techniques to elucidate the structural principles and cytoplasmic environment driving the dynamic assembly of two phase-separated compartments: Stress granules, which are RNA bodies that form rapidly in the cytoplasm upon cellular stress, and centrosomes, which are sites of microtubule nucleation. We will combine these studies with a quantitative description of the crowded nature of cytoplasm and of its local variations, to provide a direct readout of the impact of excluded volume on molecular assembly in living cells. Taken together, these studies will provide fundamental insights into the structural basis by which cells form biochemical compartments.

1 228 125 €

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

Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.

1 469 040 €

Start date: 2011-08-01, End date: 2016-07-31

Topological materials have developed rapidly in recent years, with my previous ERC-AG project 3-TOP playing a major role in this development. While so far no bulk topological superconductor has been unambiguously demonstrated, their properties can be studied in a very flexible manner by inducing superconductivity through the proximity effect into the surface or edge states of a topological insulator. In 4-TOPS we will explore the possibilities of this approach in full, and conduct a thorough study of induced superconductivity in both two and three dimensional HgTe based topological insulators. The 4 avenues we will follow are: -SQUID based devices to investigate full phase dependent spectroscopy of the gapless Andreev bound state by studying their Josephson radiation and current-phase relationships. -Experiments aimed at providing unambiguous proof of localized Majorana states in TI junctions by studying tunnelling transport into such states. -Attempts to induce superconductivity in Quantum Hall states with the aim of creating a chiral topological superconductor. These chiral superconductors host Majorana fermions at their edges, which, at least in the case of a single QH edge mode, follow non-Abelian statistics and are therefore promising for explorations in topological quantum computing. -Studies of induced superconductivity in Weyl semimetals, a completely unexplored state of matter. Taken together, these four sets of experiments will greatly enhance our understanding of topological superconductivity, which is not only a subject of great academic interest as it constitutes the study of new phases of matter, but also has potential application in the field of quantum information processing.

2 497 567 €

Start date: 2017-06-01, End date: 2022-05-31

4D reconstruction, the camera-based dense dynamic scene reconstruction, is a grand challenge in computer graphics and computer vision. Despite great progress, 4D capturing the complex, diverse real world outside a studio is still far from feasible. 4DRepLy builds a new generation of high-fidelity 4D reconstruction (4DRecon) methods. They will be the first to efficiently capture all types of deformable objects (humans and other types) in crowded real world scenes with a single color or depth camera. They capture space-time coherent deforming geometry, motion, high-frequency reflectance and illumination at unprecedented detail, and will be the first to handle difficult occlusions, topology changes and large groups of interacting objects. They automatically adapt to new scene types, yet deliver models with meaningful, interpretable parameters. This requires far reaching contributions: First, we develop groundbreaking new plasticity-enhanced model-based 4D reconstruction methods that automatically adapt to new scenes. Second, we develop radically new machine learning-based dense 4D reconstruction methods. Third, these model- and learning-based methods are combined in two revolutionary new classes of 4DRecon methods: 1) advanced fusion-based methods and 2) methods with deep architectural integration. Both, 1) and 2), are automatically designed in the 4D Real World Reconstruction Loop, a revolutionary new design paradigm in which 4DRecon methods refine and adapt themselves while continuously processing unlabeled real world input. This overcomes the previously unbreakable scalability barrier to real world scene diversity, complexity and generality. This paradigm shift opens up a new research direction in graphics and vision and has far reaching relevance across many scientific fields. It enables new applications of profound social pervasion and significant economic impact, e.g., for visual media and virtual/augmented reality, and for future autonomous and robotic systems.

1 977 000 €

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

Antibiotics have contributed to a tremendous increase in human well-being, saving many millions of lives. However, antibiotics become obsolete the more they are used as selection pressure promotes the development of resistant bacteria. The World Health Organization has proclaimed antibiotic resistance as a major global threat to public health. Today, 700,000 deaths per year are due to untreatable infections. To win the battle against antibiotic resistance, new policies affecting the supply and demand of existing and new drugs must be designed. I propose new research to identify and evaluate feasible and effective demand-side policy interventions targeting the relevant decision makers: physicians and patients. ABRSEIST will make use of a broad econometric toolset to identify mechanisms linking antibiotic resistance and consumption exploiting a unique combination of physician-patient-level antibiotic resistance, treatment, and socio-economic data. Using machine learning methods adapted for causal inference, theory-driven structural econometric analysis, and randomization in the field it will provide rigorous evidence on effective intervention designs. This research will improve our understanding of how prescribing, resistance, and the effect of antibiotic use on resistance, are distributed in the general population which has important implications for the design of targeted interventions. It will then estimate a structural model of general practitioners’ acquisition and use of information under uncertainty about resistance in prescription choice, allowing counterfactual analysis of information-improving policies such as mandatory diagnostic testing. The large-scale and structural econometric analyses allow flexible identification of physician heterogeneity, which ABRSEIST will exploit to design and evaluate targeted, randomized information nudges in the field. The result will be improved rational use and a toolset applicable in contexts of antibiotic prescribing.

1 498 920 €

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

The deep-sea floor hosts a distinct microbial biome covering 67% of the Earth’s surface, characterized by cold temperatures, permanent darkness, high pressure and food limitation. The surface sediments are dominated by bacteria, with on average a billion cells per ml. Benthic bacteria are highly relevant to the Earth’s element cycles as they remineralize most of the organic matter sinking from the productive surface ocean, and return nutrients, thereby promoting ocean primary production. What passes the bacterial filter is a relevant sink for carbon on geological time scales, influencing global oxygen and carbon budgets, and fueling the deep subsurface biosphere. Despite the relevance of deep-sea sediment bacteria to climate, geochemical cycles and ecology of the seafloor, their genetic and functional diversity, niche differentiation and biological interactions remain unknown. Our preliminary work in a global survey of deep-sea sediments enables us now to target specific genes for the quantification of abyssal bacteria. We can trace isotope-labeled elements into communities and single cells, and analyze the molecular alteration of organic matter during microbial degradation, all in context with environmental dynamics recorded at the only long-term deep-sea ecosystem observatory in the Arctic that we maintain. I propose to bridge biogeochemistry, ecology, microbiology and marine biology to develop a systematic understanding of abyssal sediment bacterial community distribution, diversity, function and interactions, by combining in situ flux studies and different visualization techniques with a wide range of molecular tools. Substantial progress is expected in understanding I) identity and function of the dominant types of indigenous benthic bacteria, II) dynamics in bacterial activity and diversity caused by variations in particle flux, III) interactions with different types and ages of organic matter, and other biological factors.

3 375 693 €

Start date: 2012-06-01, End date: 2018-05-31

Mammalian organisms possess the remarkable ability to maintain internal body temperature (Tcore) within a narrow range close to 37°C despite wide environmental temperature variations. The brain’s neural “thermostat” is made up by central circuits in the hypothalamic preoptic area (POA), which orchestrate peripheral thermoregulatory responses to maintain Tcore. Thermogenesis requires metabolic fuel, suggesting intricate connections between the thermoregulatory centre and hypothalamic circuits controlling energy balance. How the POA detects and integrates temperature and metabolic information to achieve thermal balance is largely unknown. A major question is whether this circuitry could be harnessed therapeutically to treat obesity. We have recently identified the first known molecular temperature sensor in thermoregulatory neurons of the POA, transient receptor potential melastatin 2 (TRPM2), a thermo-sensitive ion channel. I aim to use TRPM2 as a molecular marker to gain access to and probe the function of thermoregulatory neurons in vivo. I propose a multidisciplinary approach, combining local, in vivo POA temperature stimulation with optogenetic circuit-mapping to uncover the molecular and cellular logic of the hypothalamic thermoregulatory centre and to assess its medical potential to counteract metabolic syndrome. Acclimation is a beneficial adaptive process that fortifies thermal responses upon environmental temperature challenges. Thermoregulatory neuron plasticity is thought to mediate acclimation. Conversely, maladaptive thermoregulatory changes affect obesity. The cell-type-specific neuronal plasticity mechanisms underlying these changes within the POA, however, are unknown. Using ex-vivo slice electrophysiology and in vivo imaging, I propose to characterize acclimation- and obesity-induced plasticity of thermoregulatory neurons. Ultimately, I aim to manipulate thermoregulatory neuron plasticity to test its potential counter-balancing effect on obesity.

1 902 500 €

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

Formation of the Earth and the other terrestrial planets of our Solar System (Mercury, Venus and Mars) commenced 4.568 billion years ago and occurred on a time scale of about 100 million years. These planets grew by the process of accretion, which involved numerous collisions with smaller (Moon- to Mars-size) bodies. Impacts with such bodies released sufficient energy to cause large-scale melting and the formation of deep “magma oceans”. Such magma oceans enabled liquid metal to separate from liquid silicate, sink and accumulate to form the metallic cores of the planets. Thus core formation in terrestrial planets was a multistage process, intimately related to the major impacts during accretion, that determined the chemistry of planetary mantles. However, until now, accretion, as modelled by astrophysicists, and core formation, as modelled by geochemists, have been treated as completely independent processes. The fundamental and crucial aim of this ambitious interdisciplinary proposal is to integrate astrophysical models of planetary accretion with geochemical models of planetary differentiation together with cosmochemical constraints obtained from meteorites. The research will involve integrating new models of planetary accretion with core formation models based on the partitioning of a large number of elements between liquid metal and liquid silicate that we will determine experimentally at pressures up to about 100 gigapascals (equivalent to 2400 km deep in the Earth). By comparing our results with the known physical and chemical characteristics of the terrestrial planets, we will obtain a comprehensive understanding of how these planets formed, grew and evolved, both physically and chemically, with time. The integration of chemistry and planetary differentiation with accretion models is a new ground-breaking concept that will lead, through synergies and feedback, to major new advances in the Earth and planetary sciences.

1 826 200 €

Start date: 2012-05-01, End date: 2018-04-30

"Many of today's and tomorrow's computer systems are built on top of large-scale networks such as, e.g., the Internet, the world wide web, wireless ad hoc and sensor networks, or peer-to-peer networks. Driven by technological advances, new kinds of networks and applications have become possible and we can safely assume that this trend is going to continue. Often modern systems are envisioned to consist of a potentially large number of individual components that are organized in a completely decentralized way. There is no central authority that controls the topology of the network, how nodes join or leave the system, or in which way nodes communicate with each other. Also, many future distributed applications will be built using wireless devices that communicate via radio. The general objective of the proposed project is to improve our understanding of the algorithmic and theoretical foundations of decentralized distributed systems. From an algorithmic point of view, decentralized networks and computations pose a number of fascinating and unique challenges that are not present in sequential or more standard distributed systems. As communication is limited and mostly between nearby nodes, each node of a large network can only maintain a very restricted view of the global state of the system. This is particularly true if the network can change dynamically, either by nodes joining or leaving the system or if the topology changes over time, e.g., because of the mobility of the devices in case of a wireless network. Nevertheless, the nodes of a network need to coordinate in order to achieve some global goal. In particular, we plan to study algorithms and lower bounds for basic computation and information dissemination tasks in such systems. In addition, we are particularly interested in the complexity of distributed computations in dynamic and wireless networks."

1 148 000 €

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

The Acts of the Ecumenical Councils of Late Antiquity include (purportedly) verbatim minutes of the proceedings, a formal framework and copies of relevant documents which were either (allegedly) read out during the proceedings or which were later attached to the Acts proper. Despite this unusual wealth of documentary evidence, the daunting nature of the Acts demanding multidisciplinary competency, their complex structure with a matryoshka-like nesting of proceedings from different dates, and the stereotype that their contents bear only on Christological niceties have deterred generations of historians from studying them. Only in recent years have their fortunes begun to improve, but this recent research has not always been based on sound principles: the recorded proceedings of the sessions are still often accepted as verbatim minutes. Yet even a superficial reading quickly reveals widespread editorial interference. We must accept that in many cases the Acts will teach us less about the actual debates than about the editors who shaped their presentation. This does not depreciate the Acts’ evidence: on the contrary, they are first-rate material for the rhetoric of persuasion and self-representation. It is possible, in fact, to take the investigation to a deeper level and examine in what manner the oral proceedings were put into writing: several passages in the Acts comment upon the process of note-taking and the work of the shorthand writers. Thus, the main objective of the proposed research project could be described as an attempt to trace the destinies of the Acts’ texts, from the oral utterance to the manuscript texts we have today. This will include the fullest study on ancient transcript techniques to date; a structural analysis of the Acts’ texts with the aim of highlighting edited passages; and a careful comparison of the various editions of the Acts, which survive in Greek, Latin, Syriac and Coptic, in order to detect traces of editorial interference.

1 497 250 €

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

"An important driver of scientific progress has always been the envisioning of applications far beyond existing technological capabilities. Such thinking creates new challenges for physicists, driven by the groundbreaking nature of the anticipated application. In the case of laser physics, one of these applications is laser wake-field particle acceleration and possible future uses thereof, such as in collider experiments, or for medical applications such as cancer treatment. To accelerate electrons and positrons to TeV-energies, a laser architecture is required that allows for the combination of high efficiency, Petawatt peak powers, and Megawatt average powers. Developing such a laser system would be a challenging task that might take decades of aggressive research, development, and, most important, revolutionary approaches and innovative ideas. The goal of the ACOPS project is to develop a compact, efficient, scalable, and cost-effective high-average and high-peak power ultra-short pulse laser concept. The proposed approach to this goal relies on the spatially and temporally separated amplification of ultrashort laser pulses in waveguide structures, followed by coherent combination into a single train of pulses with increased average power and pulse energy. This combination can be realized through the coherent addition of the output beams of spatially separated amplifiers, combined with the pulse stacking of temporally separated pulses in passive enhancement cavities, employing a fast-switching element as cavity dumper. Therefore, the three main tasks are the development of kW-class high-repetition-rate driving lasers, the investigation of non-steady state pulse enhancement in passive cavities, and the development of a suitable dumping element. If successful, the proposed concept would undoubtedly provide a tool that would allow researchers to surpass the current limits in high-field physics and accelerator science."

1 881 040 €

Start date: 2014-02-01, End date: 2019-01-31

During the 20th century computer technology evolved from bulky, slow, special purpose mechanical engines to the now ubiquitous silicon chips and software that are one of the pinnacles of human ingenuity. The goal of the field of molecular programming is to take the next leap and build a new generation of matter-based computers using DNA, RNA and proteins. This will be accomplished by computer scientists, physicists and chemists designing molecules to execute ``wet'' nanoscale programs in test tubes. The workflow includes proposing theoretical models, mathematically proving their computational properties, physical modelling and implementation in the wet-lab. The past decade has seen remarkable progress at building static 2D and 3D DNA nanostructures. However, unlike biological macromolecules and complexes that are built via specified self-assembly pathways, that execute robotic-like movements, and that undergo evolution, the activity of human-engineered nanostructures is severely limited. We will need sophisticated algorithmic ideas to build structures that rival active living systems. Active-DNA, aims to address this challenge by achieving a number of objectives on computation, DNA-based self-assembly and molecular robotics. Active-DNA research work will range from defining models and proving theorems that characterise the computational and expressive capabilities of such active programmable materials to experimental work implementing active DNA nanostructures in the wet-lab.

2 349 603 €

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

The cell cortex is a highly dynamic layer of crosslinked actin filaments and myosin molecular motors beneath the cell membrane. It plays a central role in large scale rearrangements that occur inside cells. Many molecular mechanisms contribute to cortex structure and dynamics. However, cell scale physical properties of the cortex are difficult to grasp. This is problematic because for large scale rearrangements inside a cell, such as coherent flow of the cell cortex, it is the cell scale emergent properties that are important for the realization of such events. I will investigate how the actomyosin cytoskeleton behaves at a coarse grained and cellular scale, and will study how this emergent active behaviour is influenced by molecular mechanisms. We will study the cell cortex in the one cell stage C. elegans embryo, which undergoes large scale cortical flow during polarization and cytokinesis. We will combine theory and experiment. We will characterize cortex structure and dynamics with biophysical techniques such as cortical laser ablation and quantitative photobleaching experiments. We will develop and employ novel theoretical approaches to describe the cell scale mechanical behaviour in terms of an active complex fluid. We will utilize genetic approaches to understand how these emergent mechanical properties are influenced by molecular activities. A central goal is to arrive at a coarse grained description of the cortex that can predict future dynamic behaviour from the past structure, which is conceptually similar to how weather forecasting is accomplished. To date, systematic approaches to link molecular scale physical mechanisms to those on cellular scales are missing. This work will open new opportunities for cell biological and cell biophysical research, by providing a methodological approach for bridging scales, for studying emergent and large-scale active mechanical behaviours and linking them to molecular mechanisms.

1 500 000 €

Start date: 2011-12-01, End date: 2017-08-31

Fault-tolerant topological quantum computation has become one of the most exciting research directions in modern condensed matter physics. As a key operation the braiding of non-Abelian anyons has been proposed theoretically. Such exotic quasiparticles can be realized as zero-energy Majorana bound states at the ends of one-dimensional magnetic nanowires in proximity to s-wave superconductors in the presence of high spin-orbit coupling. In contrast to previous attempts to realize such systems experimentally, based on the growth of semiconducting nanowires or the self-assembly of ferromagnetic nanowires on s-wave superconductors, we propose to design Majorana bound states in artificially constructed single-atom chains with non-collinear spin-textures on elemental superconducting substrates using scanning tunnelling microscope (STM)-based atom manipulation techniques. We would like to study at the atomic level the formation of Shiba bands as a result of hybridization of individual Shiba impurity states as well as the emergence of zero-energy Majorana bound states as a function of chain structure, length, and composition. Moreover, we will construct model-type platforms, such as T-junctions, rings, and more complex network structures with atomic-scale precision as a basis for demonstrating the manipulation and braiding of Majorana bound states. We will make use of sophisticated experimental techniques, such as spin-resolved scanning tunnelling spectroscopy (STS) at micro-eV energy resolution, scanning Josephson tunnelling spectroscopy, and multi-probe STS under well-defined ultra-high vacuum conditions, in order to directly probe the nature of the magnetic state of the atomic wires, the spin-polarization of the emergent Majorana states, as well as the spatial nature of the superconducting order parameter in real space. Finally, we will try to directly probe the quantum exchange statistics of non-Abelian anyons in these atomically precise fabricated model-type systems.

2 499 750 €

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

New insight into ever smaller microscopic units of matter as well as in ever faster evolving chemical, physical or atomic processes pushes the frontiers in many fields in science. Pump/probe experiments turned out to be the most direct approach to time-domain investigations of fast-evolving microscopic processes. Accessing atomic and molecular inner-shell processes directly in the time-domain requires a combination of short wavelengths in the few hundred eV range and sub-femtosecond pulse duration. The concept of light-field-controlled XUV photoemission employs an XUV pulse achieved by High-order Harmonic Generation (HHG) as a pump and the light pulse as a probe or vice versa. The basic prerequisite, namely the generation and measurement of isolated sub-femtosecond XUV pulses synchronized to a strong few-cycle light pulse with attosecond precision, opens up a route to time-resolved inner-shell atomic and molecular spectroscopy with present day sources. Studies of attosecond electronic motion (1 as = 10-18 s) in solids and on surfaces and interfaces have until now remained out of reach. The unprecedented time resolution of the aforementioned technique will enable for the first time monitoring of sub-fs dynamics of such systems in the time domain. These dynamics – of electronic excitation, relaxation, and wave packet motion – are of broad scientific interest and pertinent to the development of many modern technologies including semiconductor and molecular electronics, optoelectronics, information processing, photovoltaics, and optical nano-structuring. The purpose of this project is to investigate phenomena like the temporal evolution of direct photoemission, interference effects in resonant photoemission, fast adsorbate-substrate charge transfer, and electronic dynamics in supramolecular assemblies, in a series of experiments in order to overcome the temporal limits of measurements in solid state physics and to better understand processes in microcosm.

1 296 000 €

Start date: 2008-10-01, End date: 2013-09-30

"AEROCAT aims at the elucidation of the potential of nanoparticle derived aerogels in catalytic applications. The materials will be produced from a variety of nanoparticles available in colloidal solutions, amongst which are metals and metal oxides. The evolving aerogels are extremely light, highly porous solids and have been demonstrated to exhibit in many cases the important properties of the nanosized objects they consist of instead of simply those of the respective bulk solids. The resulting aerogel materials will be characterized with respect to their morphology and composition and their resulting (electro-)catalytic properties examined in the light of the inherent electronic nature of the nanosized constituents. Using the knowledge gained within the project the aerogel materials will be further re-processed in order to exploit their full potential relevant to catalysis and electrocatalysis. From the vast variety of possible applications of nanoparticle-based hydro- and aerogels like thermoelectrics, LEDs, pollutant clearance, sensorics and others we choose our strictly focused approach (i) due to the paramount importance of catalysis for the Chemical Industry, (ii) because we have successfully studied the Ethanol electrooxidation on a Pd-nanoparticle aerogel, (iii) we have patented on the oxygen reduction reaction in fuel cells with bimetallic aerogels, (iv) and we gained first and extremely promising results on the semi-hydrogenation of Acetylene on a mixed Pd/ZnO-nanoparticle aerogel. With this we are on the forefront of a research field which impact might not be overestimated. We should quickly explore its potentials and transfer on a short track the knowledge gained into pre-industrial testing."

2 194 000 €

Start date: 2014-02-01, End date: 2019-01-31

1.2 billion people worldwide lack access to safe drinking water. Drinking water quality is threatened by newly emerging organic micro-pollutants (pesticides, pharmaceuticals, industrial chemicals) in source waters. Nanofiltration is a technology that is expected to play a key role in future water treatment processes due to its effectiveness in removal of micropollutants. However, the loss of membrane flux due to fouling is one of the main impediments in the development of membrane processes for use in drinking water treatment. Currently there is a wholly inadequate mechanistic understanding of the role of biofilm on the fouling of nanofiltration membranes. Applying techniques including confocal microscopy, force spectroscopy, and infrared spectroscopy using an experimental programme informed by a technique known as scale-down together with mathematical modelling, it is confidently expected that significant advances will be gained in the mechanistic understanding of nanofiltration biofouling. The specific objectives are 1. How is the rate of formation and extent of such biofilms influenced by the biological response to the local microenvironment? 2 Elucidate the effect of extracellular polysaccharide substances on physical properties, composition and structure of these biofilms. 3: Investigate mechanisms to enhance biofilm removal by a physical detachment process complemented by techniques that alter biofilm material properties. A more fundamental insight into the mechanisms of nanofiltration operation will help in further development of this treatment method in future water treatment processes.

1 468 987 €

Start date: 2011-10-01, End date: 2016-09-30

Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.

1 727 920 €

Start date: 2009-12-01, End date: 2014-11-30

"Significant parts of our cultural heritage are produced on the Web, yet only insufficient opportunities exist for accessing and exploring the past of the Web. The ALEXANDRIA project aims to develop models, tools and techniques necessary to archive and index relevant parts of the Web, and to retrieve and explore this information in a meaningful way. While the easy accessibility to the current Web is a good baseline, optimal access to Web archives requires new models and algorithms for retrieval, exploration, and analytics which go far beyond what is needed to access the current state of the Web. This includes taking into account the unique temporal dimension of Web archives, structured semantic information already available on the Web, as well as social media and network information. Within ALEXANDRIA, we will significantly advance semantic and time-based indexing for Web archives using human-compiled knowledge available on the Web, to efficiently index, retrieve and explore information about entities and events from the past. In doing so, we will focus on the concurrent evolution of this knowledge and the Web content to be indexed, and take into account diversity and incompleteness of this knowledge. We will further investigate mixed crowd- and machine-based Web analytics to support long- running and collaborative retrieval and analysis processes on Web archives. Usage of implicit human feedback will be essential to provide better indexing through insights during the analysis process and to better focus harvesting of content. The ALEXANDRIA Testbed will provide an important context for research, exploration and evaluation of the concepts, methods and algorithms developed in this project, and will provide both relevant collections and algorithms that enable further research on and practical application of our research results to existing archives like the Internet Archive, the Internet Memory Foundation and Web archives maintained by European national libraries."

2 493 600 €

Start date: 2014-03-01, End date: 2019-02-28

Algebras of operators on Hilbert spaces were originally introduced as the right framework for the mathematical description of quantum mechanics. In modern mathematics the scope has much broadened due to the highly versatile nature of operator algebras. They are particularly useful in the analysis of groups and their actions. Amenability is a finiteness property which occurs in many different contexts and which can be characterised in many different ways. We will analyse amenability in terms of approximation properties, in the frameworks of abstract C*-algebras, of topological dynamical systems, and of discrete groups. Such approximation properties will serve as bridging devices between these setups, and they will be used to systematically recover geometric information about the underlying structures. When passing from groups, and more generally from dynamical systems, to operator algebras, one loses information, but one gains new tools to isolate and analyse pertinent properties of the underlying structure. We will mostly be interested in the topological setting, and in the associated C*-algebras. Amenability of groups or of dynamical systems then translates into the completely positive approximation property. Systems of completely positive approximations store all the essential data about a C*-algebra, and sometimes one can arrange the systems so that one can directly read of such information. For transformation group C*-algebras, one can achieve this by using approximation properties of the underlying dynamics. To some extent one can even go back, and extract dynamical approximation properties from completely positive approximations of the C*-algebra. This interplay between approximation properties in topological dynamics and in noncommutative topology carries a surprisingly rich structure. It connects directly to the heart of the classification problem for nuclear C*-algebras on the one hand, and to central open questions on amenable dynamics on the other.

1 596 017 €

Start date: 2019-10-01, End date: 2024-09-30

Current technical sensor systems offer capabilities that are superior to human perception. Cameras can capture a spectrum that is wider than visible light, high-speed cameras can show movements that are invisible to the human eye, and directional microphones can pick up sounds at long distances. The vision of this project is to lay a foundation for the creation of digital technologies that provide novel sensory experiences and new perceptual capabilities for humans that are natural and intuitive to use. In a first step, the project will assess the feasibility of creating artificial human senses that provide new perceptual channels to the human mind, without increasing the experienced cognitive load. A particular focus is on creating intuitive and natural control mechanisms for amplified senses using eye gaze, muscle activity, and brain signals. Through the creation of a prototype that provides mildly unpleasant stimulations in response to perceived information, the feasibility of implementing an artificial reflex will be experimentally explored. The project will quantify the effectiveness of new senses and artificial perceptual aids compared to the baseline of unaugmented perception. The overall objective is to systematically research, explore, and model new means for increasing the human intake of information in order to lay the foundation for new and improved human senses enabled through digital technologies and to enable artificial reflexes. The ground-breaking contributions of this project are (1) to demonstrate the feasibility of reliably implementing amplified senses and new perceptual capabilities, (2) to prove the possibility of creating an artificial reflex, (3) to provide an example implementation of amplified cognition that is empirically validated, and (4) to develop models, concepts, components, and platforms that will enable and ease the creation of interactive systems that measurably increase human perceptual capabilities.

1 925 250 €

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

This project focuses on developing quantum field theory methods and applying them to the phenomenology of elementary particles. At the Large Hadron Collider (LHC) our current best theoretical understanding of particle physics is being tested against experiment by measuring e.g. properties of the recently discovered Higgs boson. With run two of the LHC, currently underway, the experimental accuracy will further increase. Theoretical predictions matching the latter are urgently needed. Obtaining these requires extremely difficult calculations of scattering amplitudes and cross sections in quantum field theory, including calculations to correctly describe large contributions due to long-distance physics in the latter. Major obstacles in such computations are the large number of Feynman diagrams that are difficult to handle, even with the help of modern computers, and the computation of Feynman loop integrals. To address these issues, we will develop innovative methods that are inspired by new structures found in supersymmetric field theories. We will extend the scope of the differential equations method for computing Feynman integrals, and apply it to scattering processes that are needed for phenomenology, but too complicated to analyze using current methods. Our results will help measure fundamental parameters of Nature, such as, for example, couplings of the Higgs boson, with unprecedented precision. Moreover, by accurately predicting backgrounds from known physics, our results will also be invaluable for searches of new particles.

2 000 000 €

Start date: 2017-10-01, End date: 2022-09-30

Many complex phenomena in the sciences are described by nonlinear partial differential equations, the solutions of which exhibit oscillations and concentration effects on multiple temporal or spatial scales. Our aim is to use methods from applied analysis to contribute to the understanding of the interplay of effects on different scales. The central question is to determine those quantities on the microscale which are needed to for the correct description of the macroscopic evolution. We aim to develop a mathematical framework for analyzing and modeling coupled systems with multiple scales. This will include Hamiltonian dynamics as well as different types of dissipation like gradient flows or rate-independent dynamics. The choice of models will be guided by specific applications in material modeling (e.g., thermoplasticity, pattern formation, porous media) and optoelectronics (pulse interaction, Maxwell-Bloch systems, semiconductors, quantum mechanics). The research will address mathematically fundamental issues like existence and stability of solutions but will mainly be devoted to the modeling of multiscale phenomena in evolution systems. We will focus on systems with geometric structures, where the dynamics is driven by functionals. Thus, we can go much beyond the classical theory of homogenization and singular perturbations. The novel features of our approach are - the combination of different dynamical effects in one framework, - the use of geometric and metric structures for coupled partial differential equations, - the exploitation of Gamma-convergence for evolution systems driven by functionals.

1 390 000 €

Start date: 2011-04-01, End date: 2017-03-31

Osteoarthritis (OA), the most common form of arthritis, is a serious disease of the joints affecting nearly 10% of the population worldwide. The onset of OA has been associated with defects to articular cartilage that lines the bones of synovial joints. Current strategies to treat articular cartilage defects are ineffective and/or prohibitively expensive. The aim of ANCHOR is to develop and commercialise a new medicinal product for articular cartilage regeneration that recruits endogenous bone marrow derived stem cells into an extracellular matrix derived scaffold anchored to the subchondral bone by 3D printed polymeric supports. By recruiting endogenous cells into a supporting scaffold, ANCHOR will obviate the need for pre-seeding scaffolds with cells prior to implantation into cartilage defects, thereby dramatically reducing the cost and complexity of the repair procedure. It will also overcome the need for suturing of a scaffold into a cartilage defect, which is a very time consuming and technically challenging surgical procedure. Finally, the inherent chondro-inductivity of the cartilage ECM derived scaffolds developed by the applicant will maximise the potential for hyaline cartilage regeneration. The project will leverage the applicants extensive experience in ECM derived biomaterials and 3D printing to develop a new product with significant commercial potential. The impact of ANCHOR will be multi-faceted: it will transform how damaged joints are treated by orthopaedic surgeons, it will create economic value through the commercialization of IP, and most importantly it will improve patient experience and their long-term health and well-being.

149 945 €

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

The skeleton and the sinusoidal vasculature form a functional unit with great relevance in health, regeneration, and disease. Currently, fundamental aspects of sinusoidal vessel growth, specialization, arteriovenous organization and the consequences for tissue perfusion, or the changes occurring during ageing remain unknown. Our preliminary data indicate that key principles of bone vascularization and the role of molecular regulators are highly distinct from other organs. I therefore propose to use powerful combination of mouse genetics, fate mapping, transcriptional profiling, computational biology, confocal and two-photon microscopy, micro-CT and PET imaging, biochemistry and cell biology to characterize the growth, differentiation, dynamics, and ageing of the bone vasculature. In addition to established angiogenic pathways, the role of highly promising novel candidate regulators will be investigated in endothelial cells and perivascular osteoprogenitors with sophisticated inducible and cell type-specific genetic methods in the mouse. Complementing these powerful in vivo approaches, 3D co-cultures generated by cell printing technologies will provide insight into the communication between different cell types. The dynamics of sinusoidal vessel growth and regeneration will be monitored by two-photon imaging in the skull. Finally, I will explore the architectural, cellular and molecular changes and the role of capillary endothelial subpopulations in the sinusoidal vasculature of ageing and osteoporotic mice. Technological advancements, such as new transgenic strains, mutant models or cell printing approaches, are important aspects of this proposal. AngioBone will provide a first conceptual framework for normal and deregulated function of the bone sinusoidal vasculature. It will also break new ground by analyzing the role of blood vessels in ageing and identifying novel strategies for tissue engineering and, potentially, the prevention/treatment of osteoporosis.

2 478 750 €

Start date: 2014-02-01, End date: 2019-01-31

Despite improved therapy, cardiovascular diseases remain the most prevalent diseases in the European Union and the incidence is rising due to increased obesity and ageing. The fine-tuned regulation of vascular functions is essential not only for preventing atherosclerotic diseases, but also after tissue injury, where the coordinated growth and maturation of new blood vessels provides oxygen and nutrient supply. On the other hand, excessive vessel growth or the generation of immature, leaky vessels contributes to pathological angiogenesis. Thus, the regulation of the complex processes governing vessel growth and maturation has broad impacts for several diseases ranging from tumor angiogenesis, diabetic retinopathy, to ischemic cardiovascular diseases. MicroRNAs (miRs) are small noncoding RNAs, which play a crucial role in embryonic development and tissue homeostasis. However, only limited information is available regarding the role of miRs in the vasculature. MiRs regulate gene expression by binding to the target mRNA leading either to degradation or to translational repression. Because miRs control patterns of target genes, miRs represent an attractive and promising therapeutic target to interfere with complex processes such as neovascularization and repair of ischemic tissues. Therefore, the present application aims to identify miRs in the vasculature, which regulate vessel growth and vessel remodelling and may, thus, serve as therapeutic targets in ischemic diseases. Since ageing critically impairs endothelial function, neovascularization and vascular repair, we will specifically identify miRs, which are dysregulated during ageing in endothelial cells and pro-angiogenic progenitor cells, in order to develop novel strategies to rescue age-induced impairment of neovascularization. Beyond the specific scope of the present application, the principle findings may have impact for other diseases, where deregulated vessel growth causes or accelerates disease states.

2 375 394 €

Start date: 2009-03-01, End date: 2014-02-28

The analysis of geometric and functional inequalities naturally leads to consider the extremal cases, thus looking for optimal sets, or optimal functions, or optimal constants. The most classical examples are the (different versions of the) isoperimetric inequality and the Sobolev-like inequalities. Much is known about equality cases and best constants, but there are still many questions which seem quite natural but yet have no answer. For instance, it is not known, even in the 2-dimensional space, the answer of a question by Brezis: which set, among those with a given volume, has the biggest Sobolev-Poincaré constant for p=1? This is a very natural problem, and it appears reasonable that the optimal set should be the ball, but this has never been proved. The interest in problems like this relies not only in the extreme simplicity of the questions and in their classical flavour, but also in the new ideas and techniques which are needed to provide the answers. The main techniques that we aim to use are fine arguments of symmetrization, geometric constructions and tools from mass transportation (which is well known to be deeply connected with functional inequalities). These are the basic tools that we already used to reach, in last years, many results in a specific direction, namely the search of sharp quantitative inequalities. Our first result, together with Fusco and Maggi, showed what follows. Everybody knows that the set which minimizes the perimeter with given volume is the ball. But is it true that a set which almost minimizes the perimeter must be close to a ball? The question had been posed in the 1920's and many partial result appeared in the years. In our paper (Ann. of Math., 2007) we proved the sharp result. Many other results of this kind were obtained in last two years.

540 000 €

Start date: 2010-08-01, End date: 2015-07-31

After decades of successful treatment of bacterial infections with antibiotics, formerly treatable bacteria have developed drug resistance and consequently pose a major threat to public health. To address the urgent need for effective antibacterial drugs we will develop a streamlined chemical-biology platform that facilitates the consolidated identification and structural elucidation of natural products together with their dedicated cellular targets. This innovative concept overcomes several limitations of classical drug discovery processes by a chemical strategy that focuses on a directed isolation, enrichment and identification procedure for certain privileged natural product subclasses. This proposal consists of four specific aims: 1) synthesizing enzyme active site mimetics that capture protein reactive natural products out of complex natural sources, 2) designing natural product based probes to identify their cellular targets by a method called activity based protein profiling , 3) developing a traceless photocrosslinking strategy for the target identification of selected non-reactive natural products, and 4) application of all probes to identify novel enzyme activities linked to viability, resistance and pathogenesis. Moreover, the compounds will be used to monitor the infection process during invasion into eukaryotic cells and will reveal host specific targets that promote and support bacterial pathogenesis. Inhibition of these targets is a novel and so far neglected approach in the treatment of infectious diseases. We anticipate that these studies will provide a powerful pharmacological platform for the development of potent natural product derived antibacterial agents directed toward novel therapeutic targets.

1 500 000 €

Start date: 2010-11-01, End date: 2015-10-31

This project enters the experimental investigation of anyonic quantum gases. We will study anyons – conjectured particles with a statistical exchange phase anywhere between 0 and π – in different many-body systems. This progress will be enabled by a unique approach of bringing together artificial gauge fields and quantum gas microscopes for ultracold atoms. Specifically, we will implement the 1D anyon Hubbard model via a lattice shaking protocol that imprints density-dependent Peierls phases. By engineering the statistical exchange phase, we can continuously tune between bosons and fermions and explore a statistically-induced quantum phase transition. We will monitor the continuous fermionization via the build-up of Friedel oscillations. Using state-of-the-art cold atom technology, we will thus open the physics of anyons to experimental research and address open questions related to their fractional exclusion statistics. Secondly, we will create fractional quantum Hall systems in rapidly rotating microtraps. Using the quantum gas microscope, we will i) control the optical potentials at a level which allows approaching the centrifugal limit and ii) use small atom numbers equal to the inserted angular momentum quantum number. The strongly-correlated ground states such as the Laughlin state can be identified via their characteristic density correlations. Of particular interest are the quasihole excitations, whose predicted anyonic exchange statistics have not been directly observed to date. We will probe and test their statistics via the characteristic counting sequence in the excitation spectrum. Furthermore, we will test ideas to transfer anyonic properties of the excitations to a second tracer species. This approach will enable us to both probe the fractional exclusion statistics of the excitations and to create a 2D anyonic quantum gas. In the long run, these techniques open a path to also study non-Abelian anyons with ultracold atoms.

1 497 500 €

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

Optimization problems are ubiquitous in computer science. Almost every problem involves the optimization of some objective function. However a major part of these problems cannot be solved to optimality. Therefore, algorithms that achieve provably good performance guarantees are of immense importance. Considerable progress has already been made, but great challenges remain: Some fundamental problems are not well understood. Moreover, for central problems arising in new applications, no solutions are known at all. The goal of APEG is to significantly advance the state of the art on algorithmic performance guarantees. Specifically, the project has two missions: First, it will develop new algorithmic techniques, breaking new ground in the areas of online algorithms, approximations algorithms and algorithmic game theory. Second, it will apply these techniques to solve fundamental problems that are central in these algorithmic disciplines. APEG will attack long-standing open problems, some of which have been unresolved for several decades. Furthermore, it will formulate and investigate new algorithmic problems that arise in modern applications. The research agenda encompasses a broad spectrum of classical and timely topics including (a) resource allocation in computer systems, (b) data structuring, (c) graph problems, with relations to Internet advertising, (d) complex networks and (e) massively parallel systems. In addition to basic optimization objectives, the project will also study the new performance metric of energy minimization in computer systems. Overall, APEG pursues cutting-edge algorithms research, focusing on both foundational problems and applications. Any progress promises to be a breakthrough or significant contribution.

2 404 250 €

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

Apoptotic cell death is essential for development, immune function or tissue homeostasis, and it is often deregulated in disease. Mitochondrial outer membrane permeabilization (MOMP) is central for apoptosis execution and plays a key role in its inflammatory outcome. Knowing the architecture of the macromolecular machineries mediating MOMP is crucial for understanding their function and for the clinical use of apoptosis. Our recent work reveals that Bax and Bak dimers form distinct line, arc and ring assemblies at specific apoptotic foci to mediate MOMP. However, the molecular structure and mechanisms controlling the spatiotemporal formation and range of action of the apoptotic foci are missing. To address this fundamental gap in our knowledge, we aim to unravel the composition, dynamics and structure of apoptotic foci and to understand how they are integrated to orchestrate function. We will reach this goal by building on our expertise in cell death and cutting-edge imaging and by developing a new analytical pipeline to: 1) Identify the composition of apoptotic foci using in situ proximity-dependent labeling and extraction of near-native Bax/Bak membrane complexes coupled to mass spectrometry. 2) Define their contribution to apoptosis and its immunogenicity and establish their assembly dynamics to correlate it with apoptosis progression by live cell imaging. 3) Determine the stoichiometry and structural organization of the apoptotic foci by combining single molecule fluorescence and advanced electron microscopies. This multidisciplinary approach offers high chances to solve the long-standing question of how Bax and Bak mediate MOMP. APOSITE will provide textbook knowledge of the mitochondrial contribution to cell death and inflammation. The implementation of this new analytical framework will open novel research avenues in membrane and organelle biology. Ultimately, understanding of Bax and Bak structure/function will help develop apoptosis modulators for medicine.

2 000 000 €

Start date: 2019-04-01, End date: 2024-03-31

AppSAM will unlock the synthetic capability of S-adenosyl¬methionine (SAM)-dependent methyltransferases and radical SAM enzymes for application in environmentally friendly and fully sustainable reactions. The biotechnological application of these enzymes will provide access to chemo-, regio- and stereoselective methylations and alkylations, as well as to a wide range of complex rearrangement reactions that are currently not possible through traditional approaches. Methylation reactions are of particular interest due to their importance in epigenetics, cancer metabolism and the development of novel pharmaceuticals. As chemical methylation methods often involve toxic compounds and rarely exhibit the desired selectivity and specificity, there is an urgent need for new, environmentally friendly methodologies. The proposed project will meet these demands by the provision of modular in vitro and in vivo systems that can be tailored to specific applications. In the first phase of AppSAM, efficient in vitro SAM-regeneration systems will be developed for use with methyltransferases as well as radical SAM enzymes. To achieve this aim, enzymes from different biosynthetic pathways will be combined in multi-enzyme cascades; methods from enzyme and reaction engineering will be used for optimisation. The second phase of AppSAM will address the application on a preparative scale. This will include the isolation of pure product from the in vitro systems, reactions using immobilised enzymes and extracts from in vivo productions. In addition to E. coli, the methylotrophic bacterium Methylobacter extorquens AM1 will be used as a host for the in vivo systems. M. extorquens can use C1 building blocks such as methanol as the sole carbon source, thereby initiating the biotechnological methylation process from a green source material and making the process fully sustainable, as well as being compatible with an envisaged “methanol economy”.

1 499 219 €

Start date: 2017-10-01, End date: 2022-09-30

The goal of the project is to automatically analyse human activities observed in videos. Any solution to this problem will allow the development of novel applications. It could be used to create short videos that summarize daily activities to support patients suffering from Alzheimer's disease. It could also be used for education, e.g., by providing a video analysis for a trainee in the hospital that shows if the tasks have been correctly executed. The analysis of complex activities in videos, however, is very challenging since activities vary in temporal duration between minutes and hours, involve interactions with several objects that change their appearance and shape, e.g., food during cooking, and are composed of many sub-activities, which can happen at the same time or in various orders. While the majority of recent works in action recognition focuses on developing better feature encoding techniques for classifying sub-activities in short video clips of a few seconds, this project moves forward and aims to develop a higher level representation of complex activities to overcome the limitations of current approaches. This includes the handling of large time variations and the ability to recognize and locate complex activities in videos. To this end, we aim to develop a unified model that provides detailed information about the activities and sub-activities in terms of time and spatial location, as well as involved pose motion, objects and their transformations. Another aspect of the project is to learn a representation from videos that is not tied to a specific source of videos or limited to a specific application. Instead we aim to learn a representation that is invariant to a perspective change, e.g., from a third-person perspective to an egocentric perspective, and can be applied to various modalities like videos or depth data without the need of collecting massive training data for all modalities. In other words, we aim to learn the essence of activities.

1 499 875 €

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

This project leads to one of the most dynamic regions in prehistory: the Caucasus of the 4th and early 3rd mill. BC. During this vibrant time, basic innovations emerged, which were crucial until the 19th century: wheel and wagon, copper alloys, the potter’s wheel, new breeds of woolly sheep, domestication of the horse, and others. At the same time, massive migrations from the East European steppe during the early 3rd mill. BC changed the European gene pool. The project challenges the still predominant narrative that all technical achievements stemmed from urban centres in Mesopotamia. New studies have created space for alternative hypotheses: possibly it was not the development of new techniques, but instead their adaptation from different ‘peripheries’ and their re-combination and re-configuration that formed the basis for the success of these ‘civilisations’. The Caucasus, linking Mesopotamia to the Eurasia and Europe, is for the first time in the focus of a study on innovation transfer. The study will make a major contribution by investigation of four axial innovations: wheel and wagon, metal alloys, silver metallurgy and woolly sheep. 40 wheels will be analysed by computer tomography and strontium isotopes. Some 300 copper alloys artefacts and 200 silver objects will be examined using mass spectrometry with laser ablation. 400 aDNA genom-wide analyses of humans from burials in the North Caucasus will offer the unique chance of elucidating the role of migrations for the spread of innovations. The pottery in the region, often linked to Mesopotamia, will be studied under technical aspects and is a complementary path to shed light on migration and the transfer of knowledge. Excavations in settlements will allow building up a chronology using 400 AMS 14C analyses. The project is multidisciplinary, making use of the most up-to-date analytical methods. Our long experience and reputation on both sides of the Caucasus is the ideal background for cutting-edge research.

2 487 875 €

Start date: 2019-07-01, End date: 2024-06-30

Adoptive T cell therapy (ACT) is a powerful approach to treat even advanced cancer diseases where poor prognosis calls for innovative treatments. However ACT is critically limited by insufficient T cell infiltration into the tumor, T cell activation at the tumor site and local T cell suppression. Few advances have been made in the field to tackle these limitations besides increasing T cell activation. My group has focussed on these unaddressed issues but came to realise that tackling these one by one will not be sufficient. I have developed a panel of unpublished chemokine receptors and innovative modular antibody-activated receptors which have the potential to overcome the limitations of ACT against solid tumors. This ground-breaking portfolio places my group in the unique position to address combination of synergistic receptors and enable cellular therapies in previously unsuccessful indications. My project will provide the rationale for provision of an effective cancer treatment. The goal is to develop the next generation of ACT through T cell engineering both by forced expression of migratory and activating receptors and simultaneous deletion of immune suppressive molecules by gene editing. ARMOR-T will provide the basis for further preclinical and clinical development of a pioneering cellular product devoid of the limitations of available products to date. I will prove 1) synergy between migratory and modular activating receptors, 2) feasibility to integrate gene editing into a T cell expansion protocol, 3) synergy between gene editing, migratory and modular receptors and 4) efficacy, safety and mode of action. The main work of the project will be carried out in models of pancreatic cancer. The ARMOR-T platform will subsequently be translated to other cancer entities where response to ACT is likely such as melanoma, breast or colon cancer, providing less toxic and more effective therapies to otherwise untreatable disease.

1 636 710 €

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

Based on wide-ranging sources, the project studies artistic training in pre-modern Central Europe. Up to the end of the Holy Roman Empire, the study area experienced various sizes with changing borders and different linguistic areas and jurisdictions. The project explores these aspects, referring to current research on culture-historical geography. Moreover, it will examine and, in some cases, revise the one-sided negative image of the guilds, using the example of research into historical networks and components of the dynamism of personal associations developed by neighbouring disciplines: Guild structure is viewed at times as an all-embracing, tightly knit network that permitted artists to exchange ideas and move freely and establish art markets. The cross-border research approach thus complements for the first time the historical idea of the artist as a model in social history. Up to about 1800, the artist was part of the hierarchical European society; except for the court artist, he was an artisan bound to the guilds. Numerous attempts to institutionalise artistic training and transfer it to academies succeeded only when the guilds were dissolved under Napoleon. An edition of all German-language guild and artisan regulations in Central Europe will make a hitherto little noted source type of major relevance accessible to research. One aim is to assemble a critical corpus of historical sources structured according to cities, a second, to analyse the social historical contexts, among them, synergy effects of “artistic knowledge” and training practices, the artist’s social and territorial mobility and the gender-specific inclusions and exclusions in pre-modern workshop operations. In terms of globalisation, the project can overcome topographical, methodological and content-related borders in all directions and lay the foundation for a comprehensive analysis of all of European artistic training.

1 665 117 €

Start date: 2011-06-01, End date: 2016-05-31

The objective of the present scientific proposal is the implementation of a novel approach in selective and asymmetric heterogeneous catalysis. We aim to exploit the structure and chirality of small, supported metal and bimetal clusters for triggering selective and enantioselective reactions. Our Ansatz is beyond doubt of fundamental nature. Although chemistry and in particular catalysis evolved on a largely empirical basis in the past, we strongly believe the complexity of the challenges at hand to make this a less ideal approach. In consequence, developing selective and asymmetric cluster catalysis will be based on a detailed molecular understanding and will not only require intense methodological developments for the synthesis and characterization of asymmetric catalysts and the detection of chiral and isomeric product molecules but also make use of innovative basic science in the fields of surface chemistry, cluster science, spectroscopy and kinetics. As complex as the involved challenges are, we aim at mastering the following ground-breaking steps: (a) development of cutting-edge spectroscopic methodologies for the isomer and enantiomer sensitive in situ detection of product molecules. (b) preparation and characterization of isomer- and enantioselective heterogeneous catalysts based on chiral metal clusters or molecule-cluster-complexes. (c) investigations of the selectivity and enantioselectivity of cluster based heterogeneous catalysts and formulation of concepts for understanding the observed selective and asymmetric chemistry. Besides the importance of the science carried out within this proposal, the proposed experimental methodology will also open up opportunities in other fields of chemistry like catalysis, analytical chemistry, spectroscopy, surface science, and nanomaterials.

2 301 600 €

Start date: 2010-04-01, End date: 2015-03-31

The emergence of mobile pastoralism in the Eurasian steppe five thousand years ago marked a unique transformation in human lifeways where, for the first time, people relied almost exclusively on herd animals of sheep, goat, cattle, and horses for sustenance and as symbols. Mobile pastoralism also generated altogether new forms of socio-political organization exceptional to the steppe that ultimately laid the foundation for nomadic states and empires. However, there remain striking gaps in our knowledge of how the pastoralist niche spread and evolved across Eurasia in the past and influenced cultural trajectories that frame the human-herd systems of today. Little is known about the scale of pastoralist movements connected with the initial translocation of domesticated animals, how mobility became embedded in pastoralist life, or how movement contributed to the formation of sophisticated political networks. There is a poor understanding of the character of herd animal husbandry strategies that were central to pastoralist subsistence and how these co-evolved alongside pastoralist dietary intake and ritual use of herd animals. We have a remarkably poor understanding of what pastoralists ate, especially the dietary contribution of dairy products - the quintessential dietary cornerstone food of pastoralist societies. ASIAPAST addresses these gaps through a biomolecular approach that recovers the dietary and mobility histories of pastoralists and their animals recorded in bones, teeth, and pottery. This project pairs these methods to detailed analyses of the economic and symbolic use of herd animals preserved in zooarchaeological archives. These investigations draw from materials obtained from key sites that capture the transition to mobile pastoralism, its intensification, and emergence of trans-regional political structures located across the culturally connected regions of Mongolia, Kazakhstan, Russia, Kyrgyzstan, and Uzbekistan.

1 999 145 €

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

Supramolecular assemblies – formed by the self-assembly of hundreds of protein subunits – are part of bacterial nanomachines involved in key cellular processes. Important examples in pathogenic bacteria are pili and type 3 secretion systems (T3SS) that mediate adhesion to host cells and injection of virulence proteins. Structure determination at atomic resolution of such assemblies by standard techniques such as X-ray crystallography or solution NMR is severely limited: Intact T3SSs or pili cannot be crystallized and are also inherently insoluble. Cryo-electron microscopy techniques have recently made it possible to obtain low- and medium-resolution models, but atomic details have not been accessible at the resolution obtained in these studies, leading sometimes to inaccurate models. I propose to use solid-state NMR (ssNMR) to fill this knowledge-gap. I could recently show that ssNMR on in vitro preparations of Salmonella T3SS needles constitutes a powerful approach to study the structure of this virulence factor. Our integrated approach also included results from electron microscopy and modeling as well as in vivo assays (Loquet et al., Nature 2012). This is the foundation of this application. I propose to extend ssNMR methodology to tackle the structures of even larger or more complex homo-oligomeric assemblies with up to 200 residues per monomeric subunit. We will apply such techniques to address the currently unknown 3D structures of type I pili and cytoskeletal bactofilin filaments. Furthermore, I want to develop strategies to directly study assemblies in a native-like setting. As a first application, I will study the 3D structure of T3SS needles when they are complemented with intact T3SSs purified from Salmonella or Shigella. The ultimate goal of this proposal is to establish ssNMR as a generally applicable method that allows solving the currently unknown structures of bacterial supramolecular assemblies at atomic resolution.

1 456 000 €

Start date: 2014-05-01, End date: 2019-04-30

ASTROFLOW aims to make ground-breaking progress in our physical understanding of exoplanetary mass loss, by quantifying the influence of stellar outflows on atmospheric escape of close-in exoplanets. Escape plays a key role in planetary evolution, population, and potential to develop life. Stellar irradiation and outflows affect planetary mass loss: irradiation heats planetary atmospheres, which inflate and more likely escape; outflows cause pressure confinement around otherwise freely escaping atmospheres. This external pressure can increase, reduce or even suppress escape rates; its effects on exoplanetary mass loss remain largely unexplored due to the complexity of such interactions. I will fill this knowledge gap by developing a novel modelling framework of atmospheric escape that will, for the first time, consider the effects of realistic stellar outflows on exoplanetary mass loss. My expertise in stellar wind theory and 3D magnetohydrodynamic simulations is crucial for producing the next-generation models of planetary escape. My framework will consist of state-of-the-art, time-dependent, 3D simulations of stellar outflows (Method 1), which will be coupled to novel 3D simulations of atmospheric escape (Method 2). My models will account for the major underlying physical processes of mass loss. With this, I will determine the response of planetary mass loss to realistic stellar particle, magnetic and radiation environments and will characterise the physical conditions of the escaping material. I will compute how its extinction varies during transit and compare synthetic line profiles to atmospheric escape observations from, eg, Hubble and our NASA cubesat CUTE. Strong synergy with upcoming observations (JWST, TESS, SPIRou, CARMENES) also exists. Determining the lifetime of planetary atmospheres is essential to understanding populations of exoplanets. ASTROFLOW’s work will be the foundation for future research of how exoplanets evolve under mass-loss processes.

1 999 956 €

Start date: 2019-09-01, End date: 2024-08-31

The main goal of ASTRUm is to employ stored and cooled radioactive ions for forefront nuclear astrophysics research. Four key experiments are proposed to be conducted at GSI in Darmstadt, which holds the only facility to date capable of storing highly charged radionuclides in the required element and energy range. The proposed experiments can hardly be conducted by any other technique or method. The weak decay matrix element for the transition between the 2.3 keV state in 205Pb and the ground state of 205Tl will be measured via the bound state beta decay measurement of fully ionized 205Tl81+. This will provide the required data to determine the solar pp-neutrino flux integrated over the last 5 million years and will allow us to unveil the astrophysical conditions prior to the formation of the solar system. The measurements of the alpha-decay width of the 4.033 MeV excited state in 19Ne will allow us to constrain the conditions for the ignition of the rp-process in X-ray bursters. ASTRUm will open a new field by enabling for the first time measurements of proton- and alpha-capture reaction cross-sections on radioactive nuclei of interest for the p-process of nucleosynthesis. Last but not least, broad band mass and half-life measurements in a ring is the only technique to precisely determine these key nuclear properties for nuclei with half-lives as short as a millisecond and production rates of below one ion per day. To accomplish these measurements with highest efficiency, sensitivity and precision, improved detector systems will be developed within ASTRUm. Possible applications of these systems go beyond ASTRUm objectives and will be used in particular in accelerator physics. The instrumentation and experience gained within ASTRUm will be indispensable for planning the future, next generation storage ring projects, which are launched or proposed at several radioactive ion beam facilities.

1 874 750 €

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

The Large Hadron collider (LHC) at CERN will be a milestone for the understanding of fundamental interactions and for the future of high energy physics. Four large experiments at the LHC are complementarily addressing the question of the origin of our Universe by searching for so-called New Physics. The world of particles and their interactions is nowadays described by the Standard Model. Up to now there is no single measurement from laboratory experiments which contradicts this theory. However, there are still many open questions, thus physicists are convinced that there is a more fundamental theory, which incorporates New Physics. It is expected that at the LHC either New Physics beyond the Standard Model will be discovered or excluded up to very high energies, which would revolutionize the understanding of particle physics and require completely new experimental and theoretical concepts. The LHCb (Large Hadron Collider beauty) experiment is dedicated to precision measurements of B hadrons (B hadrons are all particles containing a beauty quark). The analysis proposed here is the measurement of asymmetries between B_s particles and anti-B_s particles at the LHCb experiment. Any New Physics model will change the rate of observable processes via additional quantum corrections. Particle antiparticle asymmetries are extremely sensitive to these corrections thus a very powerful tool for indirect searches for New Physics contributions. In the past, most of the ground-breaking findings in particle physics, such as the existence of the charm quark and the existence of a third quark family, have first been observed in indirect searches. First - still statistically limited - measurements of the asymmetry in the B_s system indicate a 2 sigma deviation from the Standard Model prediction. A precision measurement of this asymmetry is potentially the first observation for New Physics beyond the Standard Model at the LHC. If no hint for New Physics will be found, this measurement will severely restrict the range of potential New Physics models.

1 059 240 €

Start date: 2011-01-01, End date: 2015-12-31

Atherosclerosis is characterized by chronic inflammation of the arterial wall. Mononuclear cell recruitment is driven by chemokines that can be deposited e.g. by activated platelets on inflamed endothelium. Chemokines require oligomerization and immobilization for efficient function, and recent evidence supports the notion that heterodimer formation between chemokines constitutes a new regulatory principle amplifying specific chemokine activities while suppressing others. Although crucial to inflammatory disease, this has been difficult to prove in vivo, primarily as chemokine heterodimers exist in equilibrium with their homodimer counterparts. We introduce the paradigm that heteromerization of chemokines provides the combinatorial diversity for functional plasticity and fine-tuning, coining this interactome. Given the relevance of chemokine heteromers in vivo, we aim to exploit this in an anti-inflammatory approach to selectively target vascular disease. In a multidisciplinary project, we plan to generate covalently-linked heterodimers to establish their biological significance. Obligate heterodimers of CC and CXC chemokines will be designed using computer-assisted modeling, chemically synthesized and cross-linked, structurally assessed using NMR spectroscopy and crystallography, and subjected to functional characterization in vitro and reconstitution in vivo. Conversely, we will develop cyclic beta-sheet-based peptides binding chemokines to specifically disrupt heteromers and we will generate mice with conditional deletion or knock-in of chemokine mutants with defects in heteromerization or proteoglycan binding to be analyzed in models of atherosclerosis. Peptides will be used for molecular imaging and chemokine heteromers will be quantified in cardiovascular patients.

2 500 000 €

Start date: 2010-04-01, End date: 2016-03-31

We propose to investigate hybrid quantum systems composed of ultracold atoms and ions. The mutual interaction of the cold neutral atoms and the trapped ion offers a wealth of interesting new physical problems. They span from ultracold quantum chemistry over new concepts for quantum information processing to genuine quantum many-body physics. We plan to explore aspects of quantum chemistry with ultracold atoms and ions to obtain a full understanding of the interactions in this hybrid system. We will investigate the regime of low energy collisions and search for Feshbach resonances to tune the interaction strength between atoms and ions. Moreover, we will study collective effects in chemical reactions between a Bose-Einstein condensate and a single ion. Taking advantage of the extraordinary properties of the atom-ion mixture quantum information processing with hybrid systems will be performed. In particular, we plan to realize sympathetic ground state cooling of the ion with a Bose-Einstein condensate. When the ion is immersed into the ultracold neutral atom environment the nature of the decoherence will be tailored by tuning properties of the environment: A dissipative quantum phase transition is predicted when the ion is coupled to a one-dimensional Bose gas. Moreover, we plan to realize a scalable hybrid quantum processor composed of a single ion and an array of neutral atoms in an optical lattice. The third direction we will pursue is related to impurity effects in quantum many-body physics. We plan to study transport through a single impurity or atomic quantum dot with the goal of realizing a single atom transistor. A single atom transistor transfers the quantum state of the impurity coherently to a macroscopic neutral atom current. Finally, we plan to observe Anderson s orthogonality catastrophe in which the presence of a single impurity in a quantum gas orthogonalizes the quantum many-body function of a quantum state with respect to the unperturbed one.

1 405 000 €

Start date: 2009-10-01, End date: 2014-09-30