ERC FUNDED PROJECTS

Every fourth woman suffers from uterine leiomyomas (ULs) – benign tumors of the uterine smooth muscle wall - at some point in premenopausal life. ULs, also called myomas or fibroids, cause a substantial health burden through symptoms such as excessive uterine bleeding, abdominal pain and infertility. These tumors are the most common cause of hysterectomy. Considering the impact that ULs have to women’s health, they are severely understudied. Our breakthrough work has shed important new light on the biology and genesis of ULs. In this ERC proposal we hypothesize that ULs can emerge through several distinct mechanisms and anticipate that each mechanism contributes to somewhat different tumor biology, clinicopathological features, and response to treatment. Also, we hypothesize that predisposing genetic variants may confer susceptibility to a particular UL subclass. To test these hypotheses, we shall create multiple layers of high-throughput data on clinicopathologically characterized ULs, including copy number variation, whole genome sequence, gene expression, and methylome profiles. Integration of these data should establish the existence and key characteristics of the different UL subclasses. Finally, we shall examine the effect of currently used drugs as well as new lead compounds in response to treatment, stratified per UL subclass. These efforts will 1) provide biological insight into molecular mechanisms driving the UL genesis and lay the scientific basis of their molecular classification, 2) describe the key characteristics of each class, 3) provide key biomarkers and molecular tools for routine diagnosis of UL subclasses, as well as clues to their targeted treatment, and 4) produce tools for detection of hereditary predisposition to ULs. This ERC project will be an important step towards non-invasive management of ULs. Reaching this goal would benefit hundreds of millions of women.

2 499 099 €

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

At a low temperature, nearly macroscopic quantum states can be sustained in superconducting (SC) Josephson junctions. Recently, these superconducting qubits have been coupled to electromagnetic resonators, in a manner analogous to cavity Quantum Electro Dynamics (QED) which describes the interaction between atoms and quantized oscillation modes in the quantum limit. On the other hand, there is yet no experimental evidence of a mode of a mechanical oscillator, such as that of a miniaturized vibrating string, to be chilled down to its quantum ground state. The main part of the proposal involves the use the coupling of Nanomechanical Resonators (NR) to SC qubits employed as artificial atoms in order to address the quantum-classical interface in mechanical motion. Similarly as the SC qubit can exchange quanta with electrical oscillators, it can, in principle, communicate with mechanical modes. The research will begin with demonstrating this kind of electromechanical interaction. In order to tackle experimental surprises, I plan on launching two parallel paths, one with a charge qubit, the other using a phase qubit. The formidable main goal is to experimentally reach the quantum ground state of a mechanical mode. I will investigate the following routes: Make a 1 GHz frequency NR, corresponding to 50 mK, which will reach the ground state at accessible temperatures. On the other hand, I propose to side-band cool a lower-frequency NR via the attached SC qubit. Near the quantum limit, I will start taking advantage of the NR as a building block of electromechanical quantum information. I also propose to push the QED setup of SC qubits coupled to electrical cavities towards more and more complicated states in order to test quantum mechanics in the nearly classical limit.

1 373 000 €

Start date: 2010-01-01, End date: 2014-12-31

Unlike previously thought the nucleus is a highly compartmentalized organelle. Both the genome and processes associated with it show non-random distribution within the nucleus. This compartmentalization has a fundamental impact on nuclear processes. However, the mechanisms driving this organization are poorly understood. I hypothesize that actin plays a key role in this process. Nevertheless, the true potential of nuclear actin has not been fully appreciated, due to two fundamental open questions in this field, namely 1) what is the biological significance of nuclear actin and 2) what is the molecular mechanism by which actin operates in the nucleus? I intend to address these key questions by manipulating actin specifically in the nucleus, and by identifying nuclear actin binding partners, respectively. My lab has recently identified the nuclear import mechanism for actin, which offers us a unique tool to manipulate nuclear actin. We will therefore create cell lines with decreased/increased nuclear actin, and analyze the consequences by using cell biological and gene expression tools, combined with deep sequencing. This will disclose the genes that depend on actin for their expression, and reveal the biological significance of nuclear actin in organizing the general nuclear landscape. To unravel the mechanisms by which actin functions in the nucleus, we will implement a novel multi-readout, fluorescence microscopy screen to identify nuclear actin binding proteins, which will be analyzed by different biochemical methods. This approach will reveal how actin is connected to nuclear machineries, and what biochemical features of actin are required to power the essential nuclear processes. These techniques will significantly broaden our understanding on the nuclear functions of actin, and thus likely reveal molecular mechanisms that regulate nuclear organization, which are highly relevant to basic biological processes, such as cell differentiation and epigenetics.

1 491 484 €

Start date: 2012-11-01, End date: 2018-08-31

Precise control over humidity and moisture levels is pertinent for various industrial processes dealing with, e.g., chemical engineering and fabrication of pharmaceuticals and semiconductor devices. In order to improve the product yields and ensure safety and high quality, accurate and reliable humidity sensing is in great demand. The dominant humidity-sensing technologies in the market are based on permittivity changes in a polymer matrix induced by water adsorption from air, resulting in changes in capacitance or conductivity. These approaches have been well established, but they are not suitable for all environments, such as those with large electromagnetic interference, high-voltage electricity, or explosive atmospheres. For several environments, remote humidity sensing would be the preferred, if not the only, option. OPTOSENSE aims at developing a remote, all-optical detection scheme for measuring relative humidity and temperature, utilizing photoswitchable azobenzene compounds. The proposed method relies on following the thermal cis-trans isomerization kinetics of hydroxyazobenzene derivatives embedded into an optically transparent matrix, which acts as the active sensing layer. The thermal isomerization kinetics of such a material is sensitive to the presence of water molecules, which adsorb to the active sensing layer from the measurement environment, providing the basis for the proposed humidity-sensing concept. Combinations of different hydroxyazobenzene derivatives and sensing wavelengths allow for simultaneous measurement of temperature and multiple hydrogen-bonding gases within a single sensing layer. In the proof-of-concept device, the whole measurement system will be integrated into optical fibers, offering a simple solution based on low-cost materials for simultaneous temperature and humidity sensing.

148 369 €

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

The goal of the proposed research is a comprehensive understanding of how evolutionary potential of pathogen populations interacts with epidemiological dynamics in natural populations. The empirical work will be conducted on the specialist fungal pathogen Podosphaera plantaginis and its host plant Plantago lanceolata in a large network of host populations. I will address the key theories of pathogen evolution, involving life-history trade-offs, competition for resources under multiple infection, and sexual reproduction. This project takes advantage of the exceptional research opportunities offered by the focal study species to test models that have not been validated with respect to realized population dynamics and the persistence of pathogen populations. I have studied the coevolutionary dynamics between P. plantaginis and P. lanceolata for several years. Unique epidemiological data have been collected annually on the occurrence of the pathogen in a network of 4000 host populations since 2001. Recently, I have generated an EST library for the pathogen that allows and facilitates genetic studies. In the planned research, I will combine laboratory experiments with large-scale population surveys, genetic studies and mathematical modelling to achieve the objectives of this proposal. The proposed research has potential for groundbreaking results on pathogen evolution and epidemiology through: i) Simultaneous study of multiple forces driving pathogen evolution and their importance in natural populations, with direct connections to epidemiology. ii) Development of new methodology for the study of obligate parasites like P. plantaginis. iii) Construction of a stochastic, spatially explicit epidemiological model predicting pathogen occurrence from one season to the next with applicability to a wide range of pathogens. iv) Identifying critical life-history stages and mechanisms for virulence evolution yield much needed insights and tools into the battle against disease.

1 498 811 €

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

Parkinson’s disease (PD) affects 1% of elderly persons and is currently incurable. PD pathogenesis is driven, at least in part, by defects in proteostasis and mitochondrial function, leading to degeneration of dopaminergic axons and neuronal death. Neurotrophic factors (NTFs) such as GDNF can protect and restore dopaminergic axons. However, attempts to deploy NTFs ectopically in therapy models, or to increase proteostasis and mitochondrial function, have met with only limited success. I hypothesize that instead of ectopic application, over-expression of relevant pathways restricted to physiologically appropriate cells provides a potent therapeutic approach to treat PD. I have made significant progress toward this goal by targeting the 3’UTR in the mouse Gdnf gene, thereby increasing expression levels without affecting the gene’s spatiotemporal expression pattern. Using this approach I have shown that elevation of endogenous GDNF levels protects mice from experimentally induced PD. Unlike ectopic GDNF application, it causes no side effects. Importantly, I have established that GDNF levels can be elevated by 3’UTR targeting in adulthood, suggesting that this strategy could be applied in humans late in life. I will use 3’UTR targeting to study the therapeutic potential of overexpressing endogenous genes, using transgenics and CRISPR-Cas9‒mediated 3’UTR editing in adult mice. First, I will increase the expression of NTFs in adult mice with experimentally induced PD. Next, I will upregulate genes important in mitochondrial function and proteostasis and test whether concurrently upregulating endogenous NTFs is a viable approach for treating PD. Third, I will use 3’UTR targeting to create a mouse model of PD in which alpha-synuclein is overexpressed, for better validation of my therapeutic strategy. Collectively, these experiments should establish proof of concept for a revolutionary, safe and effective treatment for PD.

1 999 987 €

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

The objective of the project is to find new methods for quality evaluation and modeling of room acoustics. Room acoustics has been studied over 100 years, but, e.g., the relation between objective attributes and subjective measures is not fully understood yet. This project will develop novel methods to simulate and auralize sound propagation in rooms, in particular in concert halls. The research is divided into three main topics. First, authentic auralization with physically-based room acoustics modeling methods will be studied. The recently introduced acoustic radiance transfer method is developed further to handle complex reflections from surfaces as well as diffraction. The second research topic is quality evaluation of concert hall acoustics. Novel algorithms will be developed for spatial sound analysis of a large impulse response database. Live recordings will be analyzed to find new objective quality measures. Quality assessments will also be performed subjectively with sensory evaluation methods borrowed from food industry. The third topic is related to augmented reality audio technology, which reveals the potential and richness of emerging technologies, giving a scenario of the possible future personalized mobile audio communications. The results of the project will be widely applicable in the academia, but also in every day life of people all over the world. The new knowledge in room acoustics will help to build acoustically better concert halls and public places such as libraries, shopping malls, etc. The augmented reality audio applications will help and enrich communication between humans. The concert hall acoustics research has great potential to find novel objective and subjective quality metrics. They also help in creation of authentic auralization, which will be one of the main tools for consultants in design, and in particular when explaining design results to architects, clients, and public audience.

880 224 €

Start date: 2008-07-01, End date: 2013-06-30

The progress of nanotechnology during the last decades has had a strong impact to the current research of biomedical applications, in particular against dreadful diseases such as cancer. It is estimated that more than 12 million cases of cancer are diagnosed every year worldwide. Multidrug resistance, rapid elimination by the immune system, enzymatic degradation, and poor targeting efficiency are still the major obstacles of the nanomedicines used in cancer therapy. The integration of imaging and therapeutic agents into a single carrier (theranostics) allows simultaneously detection, diagnostics, and treatment of the diseases, which may enhance both expectancy and quality of life of the patients. In the proposed project a systematic approach is taken towards developing and testing of novel multistage–multifunctional nanovectors based on the fusion between stage-2 nanoporous silicon nanoparticles and stage-1 polymersomes (fused materials = protocells, cell-like particles) for directed (targeted/personalized) therapy and multimodal imaging. With this approach it is aimed to decouple the quadruple functions of the protocell nanovectors in order to generate relevant preclinical information for rapid translation into the clinic: sufficient multifunctionality to avoid biological barriers, recognition of their targets, accounting for non-invasive in vivo imaging and delivery of therapeutics. The overall distinct and final milestones are: to ligand-anchored, co-loading of drug(s)-dye(s), and dual radiolabelling of the precisely tailored protocell nanovectors for simultaneously targeting the tumour vasculature cells, stimulating the immune system response and multimodal imaging in vivo. It is also aimed to evaluate the suitability and effectiveness of the designed nanodevices by employing in vitro models and in vivo imaging techniques and to achieve a comprehensive and deeper understanding on the cellular interactions between the protocell nanovectors and the cancer cells.

1 499 603 €

Start date: 2013-01-01, End date: 2017-12-31

"The current devices used in electronics have reached nanometre dimensions where the precise nature and location of every atom matters. To further drive the development of existing technologies and to test proposals for next generation nanoelectronics, we need tools that allow structural and electronic characterization of materials down to the atomic scale. We need to be able to measure the position and nature of the atoms, as well as the local density of electronic states at a specific energy, the charge distribution, and atomic scale magnetic properties. In addition, we need methods that allow controlled manipulation of the relevant atomic-scale details of the active region of the material, where we could pick and place atoms or molecules and create vacancies at pre-defined locations. The goal of this project is to develop such tools and apply them to three different materials systems of enormous current interest: nanostructured graphene, molecular networks and topological insulators. Progress towards using these materials in real life electronic applications is currently limited by the restricted experimental handle of their structure at the atomic scale: for example, edge structure in graphene nanostructures and contacts in molecular devices. I will use scanning probe techniques to fabricate nanoelectronic devices of atomically precise structure and explore the possibilities offered by well-defined nanostructures and spatially controlled charge and spin-doping."

1 494 448 €

Start date: 2012-02-01, End date: 2017-01-31

This project combines the forefront space physics with top-tier high performance computing. Three phenomena are above others in importance in explaining plasma behaviour in the Solar-Terrestrial system, laboratories, fusion devices, and astrophysical domains: 1) magnetic reconnection enabling energy and mass transfer between magnetic domains, 2) collisionless shocks forming due to supersonic relative flow speeds between plasmas, and 3) particle acceleration associated with both. These processes are critical in understanding the scientific foundation of space weather, i.e., harmful effects caused by enhanced radiation and dynamical processes that endanger space- and ground-based technological systems or human life. Space weather forecasts require physics-based models; however, to date only simple plasma descriptions have been used in the global context. We have developed the first 6-dimensional global magnetospheric kinetic simulation in the world, Vlasiator, promising a grand leap both in understanding fundamental space plasma physics, and in improving the accuracy of present space weather models. Combining the unique Vlasiator with newest spacecraft data, local kinetic physics can be interpreted in global context in a ground-breaking fashion. We examine in the global and self-consistent context 1. Near-Earth reconnection, 2. Ion-scale phenomena in the near-Earth shocks, 3. Particle acceleration by shocks and reconnection, 4. Inner magnetospheric wave-particle processes, and the consequent particle precipitation into the ionosphere. The proposed work is now feasible thanks to increased computational capabilities and Vlasiator. The newest space missions produce high-fidelity multi-point observations that require directly comparable global kinetic simulations offered by Vlasiator. The proposing team has an outstanding record and a leading role in global space physics modelling.

1 998 054 €

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

Quantum Field Theory (QFT) has become a universal framework in physics to study systems with infinite number of degrees of freedom. It has also had in the past significant interaction with Probability starting with Constructive QFT and rigorous statistical mechanics. The goal of this proposal is to bring QFT methods to probabilistic problems and new ideas from Probability to QFT. It concentrates on two concrete topics: (1) Renormalization Group study of rough Stochastic Partial Differential Equations, both their path wise solutions and their space-time correlations and stationary states. These equations are ubiquitous in non-equilibrium physics and they are mathematically challenging. (2) The use of Multiplicative Chaos theory in the rigorous construction and study of the Liouville Conformal Field Theory. Liouville theory is one of the most studied Conformal Field Theories in physics due to its connection to scaling limits of random surfaces and string theory. It has many mathematically puzzling features and its rigorous study is now possible. Although the physical applications of these theories are far apart on the level of mathematical methods they have a common unity based on renormalization theory that I want to utilize. I think time is ripe for a new fruitful interaction between QFT and Probability.

2 463 412 €

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

The project aims to quantify energy circulation in space plasmas. Scientifically, energy transfer is a fundamental plasma physical problem having many applications in a variety of plasma environments ranging from coronal heating on the Sun to electric heating in the ionosphere. Technologically, understanding the plasma and energy transport properties is a step toward predictions of the space environment needed for spacecraft design and operations. The space physics community lacks an accurate and self-consistent numerical model capable of describing the global plasma system in particular in the inner magnetosphere, where major magnetic storms can cause serious damage to space-borne technology. The project has two goals: 1. Novel integration of observations from ESA’s four-spacecraft Cluster mission with simulation results to gain quantitative understanding of global energy transport properties in the near-Earth space; 2. Development of a new self-consistent global plasma simulation that describes multi-component and multi-temperature plasmas to resolve non-MHD processes that currently cannot be self-consistently described by the existing global plasma simulations. The new simulation methods are now feasible due to the increased computational capabilities. Our existing simulation environment and unique analysis methods have brought exciting new results on magnetospheric energy circulation. Seven years after launch, the Cluster database is now large enough to quantitatively assess these effects. The proposing team has a long record in observational research of global energetics and a world-leading role in developing global magnetospheric computer simulations.

699 985 €

Start date: 2008-09-01, End date: 2013-08-31

This study of Renaissance dress offers a better understanding of how fashion developed at popular levels of society in Europe, 1550-1650. Drawing on documentary, visual and material evidence, it investigates fundamental questions relating to the transformation of fashion that will shed light on popular taste, dissemination, transformation and adaption of fashion, on imitation and meaning, and on changing cultural attitudes to dress among popular groups. The central goal of the project is to develop a new methodology that combines my previous experience of empirical research and theoretical models with the tradition of textile analysis and costume conservation. This involves experimenting with a range of techniques, including technical analysis of textiles, dye- and fibre analysis, and the reconstruction and visualization of historical fashions using both 16th-century recipes as well as modern digital tools such as 3D printing and digital reconstruction. This framework of dress and textile history at both scientific and experimental levels helps me to provide a more comprehensive interpretation of the value, variations, and material experiences that were associated with dress and dressing in the Renaissance, and to develop methodologies that allow us to explore new ways in which narratives from historical documents, books, images, and material objects can be created. The new historical knowledge and methodologies built during the ERC will lead to the ultimate theoretical objective of the project –to rethink the scientific foundation and theory of dress studies within the ‘new materialist’ framework. By creating a material-based approach and methodologies to the study of fashion in the context of popular groups, my research will not only build new horizons for the study of popular dress and its material and cultural significance in the Renaissance, but it will also create a theoretical model that challenges dress historians to go beyond semiotic analysis of dress.

1 999 854 €

Start date: 2017-04-01, End date: 2022-03-31

Mitochondrial DNA (mtDNA) encodes several proteins playing key roles in bioenergetics. Pathological mutations of mtDNA can be inherited or may accumulate following treatment for viral infections or cancer. Furthermore, many organisms, including humans, accumulate significant mtDNA damage during their lifespan, and it is therefore possible that mtDNA mutations can promote the aging process. There are no effective treatments for most diseases caused by mtDNA mutation. An understanding of the cellular consequences of mtDNA damage is clearly imperative. Toward this goal, we use the budding yeast Saccharomyces cerevisiae as a cellular model of mitochondrial dysfunction. Genetic manipulation and biochemical study of this organism is easily achieved, and many proteins and processes important for mitochondrial biogenesis were first uncovered and best characterized using this experimental system. Importantly, current evidence suggests that processes required for survival of cells lacking a mitochondrial genome are widely conserved between yeast and other organisms, making likely the application of our findings to human health. We will study the repercussions of mtDNA damage by three different strategies. First, we will investigate the link between a conserved, nutrient-sensitive signalling pathway and the outcome of mtDNA loss, since much recent evidence points to modulation of such pathways as a potential approach to increase the fitness of cells with mtDNA damage. Second, we will explore the possibility that defects in cytosolic proteostasis are precipitated by mtDNA mutation. Third, we will apply the knowledge and concepts gained in S. cerevisiae to both candidate-based and unbiased searches for genes that determine the aftermath of severe mtDNA damage in human cells. Beyond the mechanistic knowledge of mitochondrial dysfunction that will emerge from this project, we expect to identify new avenues toward the treatment of mitochondrial disease.

1 497 160 €

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

"The canonical problem of electromagnetic scattering in complex particulate media is solved numerically using multiple-scattering theory based on the Maxwell equations, with an exact treatment of the leading ladder and cyclical interaction diagrams. The numerical methods are validated using a nanotechnology-based scattering experiment that, simultaneously with the measurement of the full scattering matrix at arbitrary illumination and observation geometries, allows for a detailed physical characterization of the scattering object using Atomic Force Microscopy. The numerical and experimental methods will have a major impact on how knowledge is accrued on objects in our Solar System based on their scattering characteristics, with wavelengths spanning from the ultraviolet to radio, using both space-based and ground-based observing programs. The methods will have immediate applications in Earth observation, including remote sensing of the atmosphere, land, and sea."

2 749 532 €

Start date: 2013-04-01, End date: 2018-03-31

This project aims at producing new understandings of the changes in people’s sensory environmental relationships in three European cities during a particular period in history, 1950–2020. It will offer a focused window on cultural transformations of the sensory by introducing a new transgenerational methodology, ethnographic “sensobiography”. Why now? Firstly, innovative and thoroughly researched information about sensory environmental relationships is in great demand. If the findings are successful, their challenge to several conventional dichotomies will provide results whose interdisciplinary impact extends beyond cultural, sound, and music studies to areas of psychology, human geography, environmental aesthetics, and media history and theory. The research is urgent: at present we are still able to study people ethnographically who were born in the 1930s and 1940s,who therefore lived their early years without digital technologies. The moment is also ideally suited for studying generations born straight into the digital world, where there is a need to enable young and older people to maintain a many-faceted relationship with their environments. The project's three research strands are (1) transformations in mediations of sensory experience, (2) embodied remembering and senses, and (3) sensory commons. These strands will be studied via a research strategy linking individuals and groups to broader social, cultural, and political issues in the medium-sized European cities of Brighton (UK), Ljubljana (Slovenia), and Turku (Finland). Temporally and spatially tightly focused dynamic ethnography makes it possible to examine multiple modes of past and present sensory experiencing. The study of artists as “sensewitnesses” will become one of the pivotal endeavours. The project facilitates a significant step from earlier methodologies toward large-scale, multisensory, transgenerational investigation, providing significant insights into culture with a sustainable future.

1 860 264 €

Start date: 2016-08-01, End date: 2021-07-31

The past couple of years have witnessed the rise of on-chip quantum optics. This has been enabled by the fabrication of high-finesse superconducting resonators made out of coplanar waveguides, and by the coupling of these resonators to superconducting quantum bits, qubits. This so-called circuit quantum electrodynamics (cQED) has proven superior compared with the standard cavity QED with photons coupled to atoms in three-dimensional space. Namely, the coupling of the cavity photons with the qubit has reached strengths completely out of reach with traditional techniques. The energy levels and their populations in the qubits can be controlled in-situ, which has also offered the possibility prepare the quantum mechanical state of the photons in the cavity to arbitrary superpositions of the low-lying photon number states. Although great focus is put worldwide into cQED in superconducting cavities, the field of manipulation and measurement of single microwave photons outside cavities is essentially missing. This ERC starting grant project, aims to expand the power of microwave photons witnessed in cavities to free photons in waveguides. The cornerstone is the design and implementation of a single-photon click detector for microwaves. The detector will allow for the single-shot measurement of the photon state in the waveguide in a similar fashion as the photon detectors are routinely used in optical quantum computing (OQC). Thus together with the already demonstrated single-photon source, the detector will be a critical step towards quantum information processing with microwave photons. In addition to opening this novel field in physics, the detector can be utilized in the characterization of microwave components and devices at ulra-high sensitivities. In this project, we will implement a platform for such characterization and build several circuit elements to manipulate single microwave photons in the same way as beam splitters are used in OQC.

1 499 445 €

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

Very recently, it has been claimed that the Bayesian paradigm has revolutionized statistical thinking in numerous fields of research, as a considerable amount of novel Bayesian statistical models and estimation algorithms have gained popularity among scientists. Despite of the evident success of the Bayesian approach, there are also many research problems where the computational challenges have so far proven to be too exhaustive to promote wide-spread use of the state-of-the-art Bayesian methodology. In particular, due to significant advances in measurement technologies, e.g. in molecular biology, a constant need for analyzing and modeling very large and complex data sets has emerged on a wide scale during the past decade. Such needs are even anticipated to rapidly increase in near future with the current technological advances. The prevailing situation is therefore somewhat paradoxical, as the theoretical superiority of the Bayesian paradigm as an uncertainty handling framework is widely acknowledged, yet it can be unable to provide practically applicable solutions to complex scientific problems. To resolve this issue, the research project will have a focus on stochastic computational and modeling strategies to develop methods that overcome problems associated with the analysis of highly complex data sets. With these methods we aim to be able to solve a multitude of statistical learning problems for data sets which cannot yet be reliably handled in practice by any of the existing Bayesian tools. Our approaches will build upon recent advances in Bayesian predictive modeling and adaptive stochastic Monte Carlo computation, to create a novel family of parallel interacting learning algorithms. Several significant statistical modeling problems will be considered to demonstrate the potential of the developed methods. Our goal is also to provide implementations of some of the algorithms as freely available software packages to benefit concretely the scientific community.

550 000 €

Start date: 2009-11-01, End date: 2014-10-31

In this project, we develop a microwave nanobolometer invented in the ERC Starting Grant ”Single-Photon Microwave Devices: era of quantum optics outside cavities (SINGLEOUT)” into a proof of concept and carry out a market analysis and partnering with the relevant industrial players in the field. For a successful proof of concept, a self-calibrating function will be implemented into the nanobolometer, providing us with an extremely sensitive and easy-to-use detector for microwave radiation. The new device will be designed, fabricated, and measured. Due to the lack of spectrum analysers operating at cryogenic temperatures, our self-calibrating nanobolometer will provide a must-to-have piece of equipment for R&D facilities working on cryoelectronics and quantum technology. Thus licensing agreements with companies working on cryostats and cryosystems will be pursued. The key performance indicators of our nanobolometer such as detection bandwidth, dynamics range, and sensitivity will be compared with the existing room-temperature technology and a potential market share for our nanobolometer will be mapped. Especially, the opportunities for commercial systems already utilizing cryogenic components such as superconducting filters at cellular phone base stations will be investigated. During this ERC PoC project, also other business opportunities will be studied and possibilities for founding a spin-out company will be actively sought for.

149 838 €

Start date: 2016-12-01, End date: 2018-05-31

The sun provides enough energy in one minute to supply the world's energy needs for one year. The grand challenge is to turn this enormous energy potential into electricity in a cost-efficient way. So far, silicon has been most successful at this – but we are still very far away from what is achievable. One of the major problems, which is currently limiting the state-of-the-art photovoltaic solar cells, is related to the material degradation under sun light. I address this issue from a novel perspective: I study the possibility that the root cause for the degradation is related to the interaction of light with copper ions. The cornerstone of the proposal is to transfer my special knowhow from microelectronics to photovoltaics related to controlling copper behaviour in silicon. My proposal is against the commonly accepted theory, however, it could unveil many mysteries related to the degradation phenomenon. Moreover, if successful, the approach could lead to a rather simple solution in avoiding power loss: implementing charge on the surface to attract the copper ions. In this project I aim at verifying my hypotheses, formulating a new theory regarding the chemical reactions behind the degradation and finally demonstrating a method that allows fabrication of stable yet cheap silicon solar cells having potential for more than 30% power increase.

845 770 €

Start date: 2013-01-01, End date: 2017-12-31

Administrative professionalization is the hallmark of a modern state, but its origins contain a dilemma. Why there were no offices in ancient Rome? How is it possible that it nevertheless formed the model for the Western administrative state? The purpose of this project is to challenge earlier research and to propose a new model of the Roman Republican governance that integrates domestic and private space and to reinterpret its links with the Republican tradition. The significance of these issues extends much beyond this: the development of administrative space in the European context amounts to nothing less than the emergence of the concept of public. Ever since Weber, the conceptual separation of the office and its holder has defined the European way of governance. The origin of this separation of public and private has often been seen in the Roman Republican state with its strict responsibilities, term limits and defined powers of its magistracies, who operated in open public spaces. Using unconventional methodological tools to challenge the conventional view, the project explores the social and cultural dimensions of legal and administrative space, transcending modern assumptions of public and private. Two main research questions explore the confrontation of ideas and their contexts from the Roman Republic to modern Republicanism: 1) How the conflict between Republican ideals, political power and administrative practices transformed the spaces of administration? 2) How this conflict changed the social topography of Rome, the public and private spheres of governance? While much of the earlier research on Republican administration has been constitutional, focused on sovereignty or the individual magistrates, this project advances a radical new interpretation through spatial and topographical analysis. It is a comprehensive re-evaluation of the Roman administrative tradition and its links with the European heritage through the lens of administrative space.

1 994 326 €

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

The study of wild populations will benefit of increasing integration of ecological, molecular, genetic, and evolutionary approaches. The Glanville fritillary butterfly has a classic metapopulation in a network of 4,000 habitat patches in the Åland Islands, Finland, within an area of 50 by 70 km, across which population surveys have been conducted since 1993. Taking advantage of the opportunity to sample a few larvae from full-sib groups of gregarious larvae in hundreds of local populations, this project involves large-scale phenotyping and genotyping of individuals across the large metapopulation. The aim is to advance our general understanding of the genetic basis of variation in individual performance and life-time reproductive success (fitness), and the role of ongoing natural selection in population dynamics of species living in fragmented landscapes. For genotyping, we select ~1,000 SNPs from annotated genes in the recently sequenced transcriptome of this species. The same SNPs will be used to construct a pedigree for the entire metapopulation for 4 years. Two broad questions will be addressed: (1) Genetic basis of variation in dispersal, related life-history traits, and life-time reproductive success. This will be studied with association analyses, correlating individual phenotypes and genotypes to identify molecular variation with consequences for individual performance and fitness; and with pedigree analyses of natural populations, relating life-time reproductive success of individual larval groups to their phenotypic and genotypic composition. (2) Spatio-temporal population dynamics, the role of ongoing natural selection and consequences for regional adaptation. The purpose is to investigate the causes and consequences of spatio-temporal variation in population dynamics, including the role of ongoing natural selection. Mathematical modelling will be used to investigate the coupling of ecological and evolutionary dynamics in the spatial context.

2 478 999 €

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

The overall aim of the SSALT project is to throw light on the incubation of modern notions of the self and moral agency in the thought of the ancient world, their adoption and adaptation in the European and Arabic middle ages, and finally their transformation in the early modern period. This aim is approached through the twin paths of Arabic and Latin thought, both of which were in equal measure heir to the legacies of Greek rationalism and Hebrew monotheism. While most of the progress made so far in the scholarship has concentrated on Latin scholasticism, a more equally weighted investigation between the Arabic and Latin traditions can not only serve to bring to light much material that is of contemporary philosophical and ethical interest, but will also bring about a deeper understanding and appreciation of the Greek and Hebrew notions of selfhood and moral agency that form the bedrock of our culture. Once we begin to understand the similarities as well as the differences between the various thinkers frequently cited in the discussions (Aristotle and Descartes; Augustine and al-Ghazali; Avicenna and Aquinas), we can begin to discern what the theoretical implications are of committing to a certain philosophical viewpoint regarding human subjectivity and agency. Plainly, the importance of these findings reaches beyond the merely academic.

750 000 €

Start date: 2009-01-01, End date: 2012-12-31

I aim to progress substantially the understanding and applications of extremely non-wetting surfaces, tying together basic research and attractive technological advancements. The first part focuses on robust synthesis methods for superslippery liquid-repellent (SS-LR) surfaces. Furthermore, using new types of ultrasensitive force measurement for droplets, I will investigate in depth the dissipation dynamics of mobile water droplets and adhesion of droplets to surfaces, to promote understanding on low-friction surfaces. The second part aims at applying these SS-LR surfaces in droplet actuation with potential to outperform existing technologies. Additionally, the potential of SS-LR surfaces for anti-icing and for preventing bio-fouling will be investigated. The research results will have a major impact on liquid-repellent technology and will explore the fundamental physical limits of non-wetting.

1 999 468 €

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

Computer science is permeated with canonical hard problems that, a priori, have a fundamentally combinatorial structure, such as the graph coloring problem, the Steiner tree problem, the Hamiltonian cycle problem, the k-clique problem, and so forth. Accordingly, it would perhaps be quite reasonable to expect that currently the asymptotically fastest solution techniques would rely on the canonical combinatorial algorithms toolbox, such as carefully tailored combinatorial (backtrack/branching) search and case-by-case analysis, combined with, say, advanced data structures. However, this is not the case. Indeed, currently the fastest known exact/parameterized algorithms for each of the aforementioned problems (and beyond) rely on a mixed bag of advanced _algebraic_ techniques ranging from fast matrix multiplication to sieving e.g. via Möbius inversion and polynomial identity testing. This, in essence, signals that the development of systematic algorithmic principles and tools to cope with exponential-sized combinatorial spaces associated with hard search and enumeration problems is rather in its infancy. The proposed project aims to improve our understanding how such spaces can be systematically transformed and filtered using advanced algebraic and combinatorial techniques. The results of the project are of foremost interest in fundamental research in improving our understanding of computation, but potential exists also for breakthroughs that affect the computing practice, for example in connection with specific canonical tasks such as matrix multiplication or frontier applications such as motif problems in bioinformatics.

1 145 078 €

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

In this Proof-of-Concept project we will create a completely new kind of integrated energy solution platform based on thermoelectric (TE) heat energy harvesting materials that are capable of converting various types of heat flows directly into electricity. The strong basis for the project is the new oxide-based thermoelectric inorganic-organic hybrid materials discovered in the PI's ERC Advanced Grant Project “Molecular-Layer-Engineered Inorganic-Organic Hybrid Materials (LAYERENG-HYBMAT)”. These hybrid thin-film materials are fabricated by the combined atomic/molecular layer deposition (ALD/MLD) technique which uniquely allows for fabrication of highly conformal thin-film coatings on various flexible, sensitive, functional and/or nanostructured surfaces. Within this PoC project we will (1) design and construct a few prototype devices based on the flexible inorganic-organic thin-film thermoelectrics and (2) integrate the devices with novel material platforms (textiles, polymers, coatings). The novel integrated TE energy solutions will enable heat-based energy harvesting for usage scenarios that are not possible with the existing bulky and fragile TE materials/generators. In addition, (3) the market for flexible thermoelectric generators will be analysed and the commercialisation and the IPR strategies will be created for TE generation solutions.

150 000 €

Start date: 2016-05-01, End date: 2017-04-30

The structure of relativistic quantum vacuum (RQV) in our Universe is one of the main challenges in modern physics. We plan to advance our understanding of the vacuum structure and on this basis treat the most important unsolved problems in physics, such as the cosmological constant problem (why the measured vacuum energy is 120 orders of magnitude smaller than estimates from the zero point motion) and the hierarchy problem (why the masses of the known particles in the Standard Model (SM) of particle physics are much smaller than the Planck energy). The quantum vacuum shares many common properties with topological matter. The goal of the proposal is to concentrate both theoretical and experimental efforts in the investigation of connections between the topological quantum matter and RQV, to enhance understanding of topological condensed-matter systems especially in the ultra-low-temperature regime, and to apply this experience to solution of problems in SM & cosmology. As a condensed-matter system we shall use superfluid phases of liquid 3He – unique topological materials, which are the most close to SM and gravity: Superfluid 3He-A, where the low-energy excitations are topologically protected Weyl fermions, gauge bosons, and gravitons, is similar to the vacuum of SM above the electroweak transition. The fully gapped topological superfluid 3He-B with its Higgs bosons is the counterpart of SM vacuum in its broken symmetry phase. In particular, theory of relaxation of dark energy will be accompanied by experimental study of resonant decay of coherent states of non-equilibrium superfluid vacuum. Determination of the topological classes of the quantum vacua of SM including the vacua with Majorana fermions will be accompanied by experimental studies of Majorana fermions on the boundaries of topological superfluids and in cores of quantized vortices. Theory of extra Higgs bosons in SM will be accompanied by experimental study of light and heavy Higgs modes in 3He-B.

2 159 191 €

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

The response to drug therapy varies widely between individuals. Proteins involved in the absorption, distribution, metabolism and excretion of drugs play a central role in determining the concentration of a drug at the target site, and thus drug efficacy and toxicity. Transporters are membrane proteins that mediate the translocation of chemicals into and out of cells using active and passive mechanisms. We have identified a single nucleotide variant in the SLCO1B1 gene encoding the organic anion transporting polypeptide 1B1 (OATP1B1), which severely impairs the hepatic uptake of the cholesterol-lowering drug simvastatin leading to an increased systemic exposure to the drug, and a markedly increased risk of simvastatin-induced muscle toxicity. The effects of this variant differ significantly between statins, forming a rational basis for individualized lipid-lowering therapy. In addition to OATP1B1, also OATP1A2, OATP1B3, and OATP2B1 are known to transport several drugs in vitro (e.g., anticancer, cardiovascular and anti-infective drugs). However, the roles of these transporters in the pharmacokinetics of drugs in vivo in humans are unknown. The aim of this project is to systematically search for genetic variants of SLCO1A2, SLCO1B3 and SLCO2B1, which have functional significance in vivo in humans. This project will enable studies to determine the roles of these transporters in the pharmacokinetics of drugs and in the disposition of endogenous compounds in vivo, with implications for drug development and drug safety. Moreover, functionally significant variants in these genes may be used to personalize drug therapies. Overall, the project can significantly facilitate the development of new drugs and can improve the safe and effective use of drugs already in clinical use, thus increasing the health and well-being of mankind and reducing the overall costs of healthcare and drug development.

1 882 212 €

Start date: 2012-02-01, End date: 2017-01-31

Proposal Summary This is a proposal to study the growth of posted migrant work in the European Union, and the impact of this on industrial relations. Within the European Union, changes in the application of EU law have resulted in the deterritorialization of sovereign regulatory authority. National industrial relations systems have been subordinated to internal market freedoms in four recent European Court of Justice decisions. These constrain the rights of unions and governments to regulate working conditions of foreign service providers operating in their territory, in effect allowing firms to create “spaces of exception” by exploiting enclaves of alternative, deterritorialized sovereignty. For example, a Polish construction worker on a German construction site working for a Polish subcontractor does not, either in practice or in law, have the same rights as a German or Polish worker working for a German subcontractor because the employment relationship in the first instance is in many respects regulated from Poland. Sovereignty has been reconfigured, through EU law and firm practice, so that it is no longer entirely dependent on territory, but also on other contingencies. It is hypothesized that variegated sovereignty is facilitating the segmentation of labor markets, via transnational subcontracting and agency work. The project will involve fieldwork in Finland, Germany, the Netherlands, the UK, and at the EU level. The study will be based on ethnographic interviews, to record the experiences of posted migrants and 'native' workers who work with them, and 'expert' interviews of managers, union officials, and policy makers. Two industries have been selected for study: construction and metalworking, because of the prevalence of posted workers in those industries. There will also be a series of policy interviews aimed at understanding the political/legal changes taking place in the European Union which facilitate the growth of variegated sovereignty. These will be used to construct a series of comparative case studies of work sites and industries. The research team will include the Principle Investigator and three other researchers under his supervision.

913 082 €

Start date: 2011-01-01, End date: 2014-12-31

Laplace NMR (LNMR), comprising diffusion and relaxation NMR experiments, provides detailed information on the dynamics and chemical resolution of molecular systems, which is complementary to NMR spectra. Similarly to the traditional NMR spectroscopy, the information content of LNMR can be significantly enhanced by a multidimensional approach. The long experiment time and low sensitivity restrict the applicability of the multidimensional method, however. Based on spatial encoding of multidimensional data, we develop a broad range of single-scan LNMR experiments, constituting a new class of NMR experiments called ultrafast multidimensional LNMR. The method shortens the experiment time by one to three orders of magnitude as compared to the conventional method, offering unprecedented opportunity to study fast processes in real time. Furthermore, it enables boosting the sensitivity by several orders of magnitude by using nuclear spin hyperpolarization, which allows investigation of low-concentration samples. Ultrafast LNMR opens paradigm-breaking prospects in chemical, biochemical, geologic, archaeologic and medical analysis. LNMR can, e.g., provide unique information on the intra- and extracellular metabolic processes, including those of cancer cells, which facilitates diagnostics and helps to find efficient treatments, and it can be exploited in the development of new types of biosensors. Furthermore, the method reveals previously unobservable details about the phase behaviour of ionic liquids, gel and polymer formation, as well as catalysis, which are essential in understanding their performance in technological applications. LNMR is also applicable to portable, single-sided magnets, implying potential to raise the sensitivity of low-field NMR to a completely new level. This entails significant impact on mobile chemical and medical analysis. The low cost of the low-field facility renders advanced NMR analysis broadly available, even in developing countries.

2 625 000 €

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

Bacterial toxins cause devastating diseases in humans and animals, ranging from necrotic enteritis to gas gangrene and tetraplegia. While toxin synthesis probably endows these bacteria with a selective advantage in their natural habitats, toxigenesis is likely to represent a fitness cost. It is thus plausible that mild environments encourage bacteria to give up toxin production, or reduce the number of toxigenic cells in populations. The cellular strategies bacteria use to silence toxin production and to establish stably non-toxigenic subpopulations represent targets for innovative antitoxin and vaccine strategies that can be utilized by the food, feed, medical, and agricultural sectors. I have found the first repressor that blocks the production of the most poisonous substance known to mankind, botulinum neurotoxin (BOT). This toxin, also known as “botox”, kills in nanogram quantities and is produced by the notorious food pathogen, Clostridium botulinum. In whyBOTher, I will extend the knowledge from this single regulator to comprehensive understanding of how C. botulinum cultures coordinate BOT production between single cells and cell subpopulations in response to their physical and social environment, and which genetic and plastic cellular strategies the cells take to attenuate BOT production in short and long term. I will experimentally force evolution of BOT-producing and non-producing cell lines, and explore the genetic, epigenetic, and cellular factors that explain the emergence of the two cell lines. To achieve this goal, I will extend the research on C. botulinum biology in two dimensions: from population level to fluorescent single-cell biology, and from genomic information to functional analysis of regulatory and metabolic networks controlling BOT production. whyBOTher represents an unprecedented research effort into regulation of bacterial toxins, and introduces a shift in paradigm from population-level observations to the life of single bacterial cells.

2 000 000 €

Start date: 2017-01-01, End date: 2021-12-31