ERC FUNDED PROJECTS

Computer graphics technology for realistic rendering has improved dramatically; however, the technology to create scene models to be rendered, e.g., for movies, has not developed at the same pace. In practice, the state of the art in model creation still requires months of complex manual design, and this is a serious threat to progress. To attack this problem, computer graphics and computer vision researchers jointly developed methods that capture scene models from real world examples. Of particular importance is the capturing of moving scenes. The pinnacle of dynamic scene capture technology in research is marker-less performance capture. From multi-view video, they capture dynamic surface and texture models of the real world. Performance capture is hardly used in practice due to profound limitations: recording is usually limited to indoor studios, controlled lighting, and dense static camera arrays. Methods are often limited to single objects, and reconstructed shape detail is very limited. Assumptions about materials, reflectance, and lighting in a scene are simplistic, and we cannot easily modify captured data. In this project, we will pioneer a new generation of performance capture techniques to overcome these limitations. Our methods will allow the reconstruction of dynamic surface models of unprecedented shape detail. They will succeed on general scenes outside of the lab and outdoors, scenes with complex material and reflectance distributions, and scenes in which lighting is general, uncontrolled, and unknown. They will capture dense and crowded scenes with complex shape deformations. They will reconstruct conveniently modifiable scene models. They will work with sparse and moving sets of cameras, ultimately even with mobile phones. This far-reaching, multi-disciplinary project will turn performance capture from a research technology into a practical technology, provide groundbreaking scientific insights, and open up revolutionary new applications.

1 480 800 €

Start date: 2013-09-01, End date: 2018-08-31

The change from reproduction by outbreeding to selfing is one of the most frequent evolutionary transitions in plants. This transition is generally accompanied by changes in flower morphology and function, termed the selfing syndrome, including a reduction in flower size and a more closed flower structure. While the loss of self-incompatibility is relatively well understood, little is known about the molecular basis of the associated morphological changes and their evolutionary history. We will address these problems using the species pair Capsella grandiflora (the ancestral outbreeder) and C. rubella (the derived selfing species) as a genetically tractable model. We have established recombinant inbred lines from a cross of C. grandiflora x C. rubella and mapped quantitative trait loci affecting flower size and flower opening. Using this resource, the proposal will address four objectives. (1) We will isolate causal genes underlying the variation in flower size and opening, by combining genetic mapping with next-generation sequencing. (2) We will characterize the developmental and molecular functions of the isolated genes in Capsella and Arabidopsis. (3) We will dissect the molecular basis of the different allelic effects of the causal genes to determine which kinds of mutations have led to the morphological changes. (4) Based on population-genetic analyses of the isolated genes, the evolutionary history of the morphological changes will be retraced. Together, these strands of investigation will provide a detailed understanding of general processes underlying morphological evolution in plants.

1 480 826 €

Start date: 2010-12-01, End date: 2016-11-30

The proposed project will significantly improve the insight in the processes that have changed a comet nucleus or asteroid since their formation. These processes typically go along with activity, the observable release of gas and/or dust. Understanding the evolutionary processes of comets and asteroids will allow us to answer the crucial question which aspects of these present-day bodies still provide essential clues to their formation in the protoplanetary disc of the early solar system. Ground-breaking progress in understanding these fundamental questions can now be made thanks to the huge and unprecedented data set returned between 2014 and 2016 by the European Space Agency’s Rosetta mission to comet 67P/Churyumov-Gerasimenko, and by recent major advances in the observational study of active asteroids facilitated by the increased availability of sky surveys and follow-on observations with world-class telescopes. The key aims of this proposal are to - Obtain a unified quantitative picture of the different erosion processes active in comets and asteroids, - Investigate how ice is stored in comets and asteroids, - Characterize the ejected dust (size distribution, optical and thermal properties) and relate it to dust around other stars, - Understand in which respects comet 67P can be considered as representative of a wider sample of comets or even asteroids. We will follow a highly multi-disciplinary approach analyzing data from many Rosetta instruments, ground- and space-based telescopes, and connect these through numerical models of the dust dynamics and thermal properties.

1 484 688 €

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

The impressive progress in synthetic organic chemistry during the past century has propelled this discipline to its current central place as the key enabling technology in the physical and life sciences. Despite these remarkable advances, our ability to construct molecules of even moderate structural complexity remains unsatisfactory, since these syntheses continue to be inefficient, rely on a high number of reaction steps, and generate undesired, often toxic waste. These features led to the general need for greener transformations that will stimulate the development of more sustainable chemical industries. Conventional approaches in synthetic organic chemistry make use of starting materials displaying specific functional groups, the installation of which results in costly reaction and purification steps. Therefore, an environmentally-sound and economically-attractive alternative is represented by the direct functionalization of ubiquitous carbon-hydrogen (C–H) bonds. These transition-metal-catalyzed processes avoid prefunctionalization strategies, prevent the formation of undesired waste, and thus enable an overall streamlining of organic synthesis. While considerable recent progress has been accomplished in C–H bond functionalizations, available methodologies continue to be limited in scope, and key challenges are still to be overcome. Establishing a full set of sustainable C–H bond functionalization protocols will undeniably have a tremendous impact on various applied areas, such as drug discovery, chemical industries or material sciences.

1 499 338 €

Start date: 2012-10-01, End date: 2017-09-30

Dikes and sills are large sheet-like intrusions transporting and storing magma in the Earth’s crust. When propagating, they generate seismicity and deformation and may lead to volcanic eruption. The physics of magma-filled structures is similar to that of any fluid-filled reservoir, such as oil fields and CO2 reservoirs created by sequestration. This project aims to address old and new unresolved challenging questions related to dike propagation, sill emplacement and in general to the dynamics of fluid and gas-filled reservoirs. I propose to focus on crustal deformation, induced seismicity and external stress fields to study the signals dikes and sills produce, how they grow and why they reactivate after years of non-detected activity. I will combine experimental, numerical and analytical techniques, in close cooperation with volcano observatories providing us with the data necessary to validate our models. In the lab, I will simulate magma propagation injecting fluid into solidified gelatin. I will also contribute to a project, currently under evaluation, on the monitoring of a CO2 sequestration site. At the same time, I will address theoretical aspects, extending static models to dynamic cases and eventually developing a comprehensive picture of the multi faceted interaction between external stress field, magma and rock properties, crustal deformation and seismicity. I also plan, besides presenting my team’s work in the major national and international geophysical conferences, to produce, with technical support from the media services of DKRZ (Deutsches Klimarechenzentrum), an audiovisual teaching DVD illustrating scientific advances and unresolved issues in magma dynamics, in the prediction of eruptive activity and in the physics of reservoirs.

1 507 679 €

Start date: 2010-07-01, End date: 2015-06-30

Sphingolipids including ceramides are building blocks of cell membranes, but also act as regulated intracellular messenger molecules. Emerging data indicate that sphingolipids are dynamically regulated by nutrients, and in turn control systemic metabolism, for example, by modulating insulin secretion, proliferation and cell death of pancreatic beta cells. Dysfunction and death of beta cells are key events during the development of diabetes, from which more than 400 million patients suffer worldwide. While pharmacological inhibition of general ceramide biosynthesis is protective against diabetes in animal studies, side effects of total loss of ceramides prevent medical implementation. The de novo synthesis of ceramides is fully dependent on six ceramide synthase enzymes (CerS 1-6), which are expressed in a tissue specific manner, and generate ceramides with different chain lengths. Currently, the functional roles and regulatory modulators of each CerS are unknown in pancreatic beta cells. Importantly, the downstream mechanisms by which ceramides impair beta cell function and eventually cause diabetes are not defined. Here, I propose to combine genomics, proteomics and lipidomics to assess the function of ceramide synthases expressed in mouse and human beta cells. Furthermore, both the subcellular localisation and the post-translational modifications of CerS will be determined. The ceramide-interacting proteins mediating the deleterious effects of ceramides will be identified by lipid-protein crosslinking and functionally tested. Finally, in a translational approach, we will test the ability of recently generated novel specific CerS inhibitors with improved specificity to ameliorate beta cell stress, and improve insulin secretion in mouse and human beta cells. In sum, we will identify, characterize, validate and target ceramide synthases involved in beta cell biology and development of diabetes.

1 492 314 €

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

Tetralogy of Fallot (TOF) is the most common congenital heart disease (CHD) occurring 1 in 3000 births. Genetic studies have identified numerous genes that are responsible for inherited and sporadic forms of TOF, most of which encode key molecules that are part of regulatory networks controlling heart development. The identification of two populations of cardiac precursors, one exclusively forming the left ventricle and the second the outflow tract, the right ventricle and the atria, has suggested a new approach to interpret CHDs, in particular in TOF, not as a defect in a specific gene, but rather as a defect in the formation, expansion, and differentiation of defined subsets of embryonic cardiac precursors. The LIM-homeodomain transcription factor ISL1 marks the second population of cardiac progenitors, but little is known about its downstream targets, and how causative genes of CHDs affect cell-fate decisions in the ISL1 lineage. The main goals of this research program are: (1) to decipher the functional role of Isl1 downstream targets identified by a genome-wide ChIP-Seq approach; (2) to generate induced pluripotent stem (iPS) cells from controls and patients affected by severe forms of TOF characterized by defects in heart compartments known to derive from ISL1 cardiac progenitors; (3) to direct these iPS cells to ISL1+ cardiovascular precursors and identify cell-surface makers enabling their antibody-based purification; and (4) to use TOF-iPS-derived ISL1+ progenitors as an unique in vitro model system for deciphering molecular mechanisms that govern the fates and differentiation of this progenitor lineage and determine the pathological phenotype seen in TOF. This work will shed light on the molecular mechanisms of ISL1+ cardiac progenitor lineage specification and will give important new insights into the mechanisms of how alterations in transcriptional and epigenetic programs translate to a distinct structural defect during cardiogenesis.

1 499 996 €

Start date: 2011-03-01, End date: 2017-02-28

CHEMO-RISK aims for a novel scientifically sound chemical risk assessment paradigm that integrates exposure and effect assessment of a broad range of chemicals into a single procedure and provides information relevant to ecosystem and human health. The key innovation is polymer “chemometers” that will be equilibrated with their surroundings and deliver information on the pollutant’s chemical activity in the environment, biota, and humans. A chemometer functions analogously to a thermometer, but instead of the temperature, it yields a measure of chemical activity. Chemical activity in turn indicates the thermodynamic potential for, e.g., partitioning, biouptake and toxicity. CHEMO-RISK aims at breaking the current paradigm in environmental risk assessment of single chemicals that disregards bioavailability, ignores mixture effects, lacks site-specificity and is difficult to extrapolate to human health. The chemometer extracts will be investigated using top-notch (a) GC and LC/Orbitrap chemical analysis to characterise the pollutant mixtures and (b) cell-based reporter gene bioassays to determine mixture effects covering baseline toxicity, specific (e.g., endocrine disruption) and reactive (e.g., genotoxicity) modes of toxic action and adaptive stress responses. Within CHEMO-RISK, the following important research questions will be tackled: (A) Which processes drive the enrichment of pollutants in aquatic biota on a thermodynamic basis? (B) How do pollutants distribute within an organism, and which effects do they elicit at the key target sites? (C) Can we apply everyday-life items such as eyeglass-nose pads to replace invasive sampling in human health risk assessment? (D) To which degree can non-target analysis of chemometer extracts explain the observed toxicity profiles across media? By combining all these research efforts, CHEMO-RISK will provide a unified risk assessment paradigm with risk-based trigger values distinguishing acceptable from unacceptable effects.

1 496 030 €

Start date: 2017-05-01, End date: 2022-04-30

China s economy has expanded at breakneck speed to become the 3rd largest trading country in the world and the largest recipient of foreign direct investment (FDI). Entry into the WTO in 2001 was a landmark event in this ongoing process and I propose to study several channels through which it spurred China s industrial development. Crucially, I will take an integrated view of the different ways in which Chinese and Western firms interact: through trade flows, as suppliers or competitors, FDI, or knowledge transfers. First, I investigate the existence and magnitude of a causal link from the trade reforms to productivity growth. Second, I look for evidence of capability upgrading, such as increased production efficiency, an ability to produce higher quality products, or introduce new products by innovating. Third, I study the mechanisms for the impact of trade and FDI on local firms, in particular assessing the relative importance of increased market competition and the transfer of know-how from foreign firms. For this analysis, I draw heavily on a unique data set. Information on the universe of Chinese manufacturing firms is being linked to the universe of Chinese trade transactions. These are unique research tools on their own, but as a linked data set, the only comparable one in the world is for the U.S. economy. The Chinese data has the advantage to contain detailed information on FDI, distinguishes between ordinary and processing trade, and contains information on innovation, such as R&D and sales of new goods. Answering the above questions is important for other developing countries wanting to learn from China s experience and for Western firms assessing how quickly Chinese firms will become viable suppliers of sophisticated inputs or direct competitors. By estimating models that are explicitly derived from new theories, I advance the literature at the interaction of international and development economics, industrial organization, economic geography.

944 940 €

Start date: 2010-02-01, End date: 2016-01-31

The principle objective of this proposal is to validate fluorinated glyco-structures as effective carbohydrate mimics for the next frontier in pharmaceutical research. Herein we propose to capitalise on the major advances in statistical data analysis which are unravelling the complexity of mammalian and bacterial “glycospace”. Molecular mimicry is a powerful drug design approach. It is therefore envisaged to develop a focussed programme of research to validate fluorinated glycostructures, and in particular 2-fluoro sugars, as carbohydrate mimics for chemical biology, exploiting the ubiquitous role of carbohydrates in molecular recognition. Salient features of the 2-fluoro substituent include (i) enhanced hydrolytic stability to enzymatic degradation, (ii) the presence of a NMR active reporter nucleus (19F) for facile analysis, and (iii) the possibility for molecular imaging application when using 18F labelled glycostructures. Phase one of this project will aim to develop synthetic routes to the target fluoro-glycostructures. This will involve a substantial component of physical organic chemistry including conformational analysis, advanced 19F NMR spectroscopy and the possible isolation of oxo-carbenium analogues by exploiting advances in the development of large, weakly co-ordinating anions. From first principle reaction design and development, through a basic understanding of conformation and reactivity, phase 2 will focus on the application of these materials for chemical biology applications. Phase 2 will then heavily focus on the application of complex oligosaccharides containing the PET active 18F moiety. It is envisaged that by exploiting the ubiquitous role of carbohydrates in molecular recognition that this would conceivably lead to the development of selective imaging agents, thus bypassing the current problem of relying on the metabolically controlled distribution of the commonly used PET tracer 2-fluorodeoxy glucose (18F-FDG).

1 253 880 €

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

The three-dimensional organization of the genome, which strikingly correlates with gene activity, is critical for many cellular processes. The evolution of molecular techniques has allowed us to unveil chromatin structure at an unprecedented resolution. The most intriguing chromatin structures observed in animals are TADs (Topologically Associating Domains), which represent the functional and structural chromatin domains demarcating the genome. Structural proteins such as insulators proteins, on the other hand, have been shown to play crucial roles in mediating the formation of TADs. However, major structural factors relevant to chromatin structure are still waiting to be discovered in land plants. My preliminary work shows that TADs are widely distributed across the rice genome, and motif sequence analysis suggests the enrichment of plant-specific transcription factors at TAD boundaries, which jointly give rise to an exciting hypothesis that these proteins might be the long-sought-after insulators in land plants. By using various state-of-the-art molecular and computational tools, this timely project aims to fill a huge gap in plant functional genomics and substantially advance our understanding of three-dimensional chromatin structure. This project consists four major aims, which collectively will uncover the identities of plant insulator proteins and generate insights into the dynamics of structural chromatin domains during stress adaptation. Aim 1 will identify and characterize the stability and plasticity of functional chromatin domains in the rice genome during temperature stress adaptation. Aim 2 will identify insulator elements and other structural features of chromatin packing in the Marchantia polymorpha genome from a structural genomics approach. Aim 3 will establish the role of candidate proteins as plant insulators. Lastly, Aim 4 will generate functional insights into the molecular mechanism by which plant insulators shape the three-dimensional genome.

1 498 216 €

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

The three-dimensional organization of chromosomes is necessary for hereditary fidelity and gene regulation. Recent studies have found that eukaryotic interphase chromosomes are spatially organized in compartments, chiefly topologically associated domains (TADs), in a hierarchical order of nested chromatin loops, coining the term “chromosome folding”. TADs are clusters of genes and regulatory elements that are confined to their genomic compartment by spatially constricting their accessible range of action. The folded structure of chromosomes through long-range loops enables mutual interactions of distant genomic loci that otherwise would not be in contact. While crosslinking-based chromosome conformation capture (3C) techniques have revealed the underlying structure of interphase chromosomes, the molecular mechanism of how chromosome-organizing proteins, such as the insulator CTCF or the structural maintenance of chromosomes (SMC) complex cohesin build the chromosomal scaffold and contribute to genomic organization, is not understood. Due to the complexity of the processes involved, biochemical information on how chromosomal proteins contribute to the establishment of TADs is scarce. I have previously demonstrated that single molecule techniques can be used to study the interactions of single cohesin complexes with DNA, chromatin and DNA-bound proteins and to resolve processes that are inaccessible in bulk biochemical experiments. In this project, I will use and expand the high-throughput single molecule technique of DNA curtains to study the molecular details of how chromosomal scaffolding proteins and genetic insulators form the basis for the three-dimensional folding of chromosomes. My experiments will build a novel experimental platform to study the dynamics of chromosomal configuration and maintenance in a reconstituted single molecule assay and will reveal the molecular details that drive the organization of chromosomes into hierarchically organized structures.

1 499 350 €

Start date: 2018-07-01, End date: 2023-06-30

Recent cancer genome analyses have led to the discovery of a process involving massive genome structural rearrangement (SR) formation in a one-step, cataclysmic event, coined chromothripsis. The term chromothripsis (chromo from chromosome; thripsis for shattering into pieces) stands for a hypothetical process in which individual chromosomes are pulverised, resulting in a multitude of fragments, some of which are lost to the cell whereas others are erroneously rejoined. Compelling evidence was presented that chromothripsis plays a crucial role in the development, or progression of a notable subset of human cancers – thus, tumorigensis models involving gradual acquisitions of alterations may need to be revised in these cancers. Presently, chromothripsis lacks a mechanistic basis. We recently showed that in childhood medulloblastoma brain tumours driven by Sonic Hedgehog (Shh) signalling, chromothripsis is linked with predisposing TP53 mutations. Thus, rather than occurring in isolation, chromothripsis appears to be prone to happen in conjunction with (or instigated by) gradually acquired alterations, or in the context of active signalling pathways, the inference of which may lead to further mechanistic insights. Using such rationale, I propose to dissect the mechanism behind chromothripsis using interdisciplinary approaches. First, we will develop a computational approach to accurately detect chromothripsis. Second, we will use this approach to link chromothripsis with novel factors and contexts. Third, we will develop highly controllable cell line-based systems to test concrete mechanistic hypotheses, thereby taking into account our data on linked factors and contexts. Fourth, we will generate transcriptome data to monitor pathways involved in inducing chromothripsis, and such involved in coping with the massive SRs occurring. We will also combine findings from all these approaches to build a comprehensive model of chromothripsis and its associated pathways.

1 471 964 €

Start date: 2014-04-01, End date: 2019-01-31

The cilium is an organelle that protrudes from the cell body and is responsible for the motility of unicellular organisms and of vertebrate cell types such as sperm cells. In addition, most vertebrate cells have primary non-motile cilia important for sensory reception and signalling. The assembly and function of cilia rely on intraflagellar transport (IFT), the bi-directional movement of macromolecules between the cell body and the cilium. As cilia do not contain ribosomes, IFT is required to move the approximately 600 different ciliary proteins from their site of synthesis in the cell body to their site of function in the cilium. IFT is powered by kinesin and dynein motors, which move cargoes along the microtubule-based axoneme of the cilium. The interaction between motors and cargoes is mediated by the IFT complex, a 1.6 MDa complex formed by 20 different proteins. Despite the importance of the IFT complex, very little is known about its architecture and how it is regulated. In this proposal, we want to address both aspects using a combination of structural and functional studies. The structural analysis of the IFT complex is daunting given its size and complexity. We are proceeding with the biochemical reconstitution of the core subcomplexes, which we plan to analyze using X-ray crystallography and electron microscopy. To date, we have solved the X-ray structure of a dimeric complex between an IFT GTPase and its binding factor, and have reconstituted one of the two core complexes (the 8-subunit IFT-B complex) in amounts and purity suitable for structural studies. While these studies are progressing, we plan to use similar approaches to tackle the other core complex (IFT-A) and the plethora of ciliary GTPases, with the ambitious goal of understanding the architecture and regulation of the the entire IFT complex. This will shed light on the molecular basis of ciliogenesis and the pathological consequences of its disruption.

1 498 650 €

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

The idea to freely control the atomic-scale structure of matter has intrigued scientists for many decades. The low-temperature scanning probe microscope (LT SPM) has become the instrument of choice for this task since it allows the rearrangement of atoms and molecules on a surface. There is, however, no generic SPM-based method for the manipulation of molecules beyond lateral rearrangement. The goal of this project is to develop controlled mechanical manipulation of molecules (CM3) in which a LT SPM is used to handle large organic molecules in three dimensions with optimal control over position, orientation and shape. CM3 will become a game-changing technique for research on molecular properties and molecular-scale engineering, because it combines fully deterministic manipulation with broad access to molecular degrees of freedom for the first time. In CM3 the tip is attached to a single reactive atom within a molecule. Tip displacement guides the molecule into a desired conformation while the surface provides a second (weaker) fixation. The fundamental challenge addressed by this project is the identification of precise molecular conformations at any time during manipulation. The solution is a big data approach where large batches of automatically recorded SPM manipulation data are structured using machine learning and interpreted by comparison to atomistic simulations. The key idea is a comparison of entire conformation spaces at once, which is robust, even if the theory is not fully quantitative. The obtained map of the conformation space is used to determine molecular conformations during manipulation by methods of control theory. The effectiveness of this approach will be demonstrated in experiments that unambiguously reveal the structure-conductance relation for a series of molecules and that realize the engineering paradigm of piecewise assembly on the molecular scale by constructing a direct current rotor / motor from individual components.

1 465 944 €

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

The continued increase in the atmospheric concentration of CO2 due to anthropogenic emissions is leading to significant changes in climate, with the industry accounting for one-third of all the energy used globally and for almost 40% of worldwide CO2 emissions. Fast actions are required to decrease the concentration of this greenhouse gas in the atmosphere, value that has currently reaching 400 ppm. Among the technological possibilities that are on the table to reduce CO2 emissions, carbon capture and storage into geological deposits is one of the main strategies that is being applied. However, the final objective of this strategy is to remove CO2 without considering the enormous potential of this molecule as a source of carbon for the production of valuable compounds. Nature has developed an effective and equilibrated mechanism to concentrate CO2 and fixate the inorganic carbon into organic material (e.g., glucose) by means of enzymatic action. Mimicking Nature and take advantage of millions of years of evolution should be considered as a basic starting point in the development of smart and highly effective processes. In addition, the use of amino-acid salts for CO2 capture is envisaged as a potential approach to recover CO2 in the form of (bi)carbonates. The project CO2LIFE presents the overall objective of developing a chemical process that converts carbon dioxide into valuable molecules using membrane technology. The strategy followed in this project is two-fold: i) CO2 membrane-based absorption-crystallization process on basis of using amino-acid salts, and ii) CO2 conversion into glucose or salts by using enzymes as catalysts supported on or retained by membranes. The final product, i.e. (bi)carbonates or glucose, has a large interest in the (bio)chemical industry, thus, new CO2 emissions are avoided and the carbon cycle is closed. This project will provide a technological solution at industrial scale for the removal and reutilization of CO2.

1 302 710 €

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

Nowadays human intellectual product is increasingly produced and disseminated solely in digital form. The capability of digital data for effortless reproduction and transfer has lead to a true revolution that impacts every aspect of human creativity. Nevertheless, as with every technological revolution, this digital media revolution comes with a dark side that, if left unaddressed, it will limit its impact and may counter its potential advantages. In particular, the way we produce and disseminate digital content today does not lend itself to controlling the way data move and change. It turns out that the power of being digital can be a double-edged sword: the ease of production, dissemination and editing also implies the ease of misappropriation, plagiarism and improper modification. To counter the above problems, the proposed research activity will focus on the development of a new generation of enabling cryptographic technologies that have the power to facilitate the appropriate controls for data movement. Using the techniques developed in this project it will be feasible to build digital content distribution systems where content producers will have the full possible control on the dissemination of their intellectual product, while at the same time the rights of the end-users in terms of privacy and fair use can be preserved. The PI is uniquely qualified to carry out the proposed research activity as he has extensive prior experience in making innovations in the area of digital content distribution as well as in the management of research projects. As part of the project activities, the PI will establish the CODAMODA laboratory in the University of Athens and will seek opportunities for technology transfer and interdisciplinary work with the legal science community.

1 212 960 €

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

The Holocene record of atmospheric CO2 and methane concentrations is an enigma. Concentrations of both gases increased from the beginning of the epoch 11,700 years ago to about 10,000 BP, then declined for several thousand years, but by 6000 BP, concentrations of both gases were steadily increasing again. This mid-late Holocene rise in greenhouse gases is unusual; similar patterns are not observed during previous interglacials. While various mechanisms have been proposed to explain these changes in Holocene CO2 and methane, there is one undisputed feature of this epoch that we know is different from the rest of Earth history: the existence of behaviorally modern humans. How humanity could have influenced the Holocene increase in CO2 and methane concentrations is the subject of the COEVOLVE project. In an interdisciplinary study that combines the social and natural sciences, we will reconstruct anthropogenic CO2 and methane emissions over the Holocene using a state-of-the-art model of terrestrial biogeochemistry and earth surface processes. The novelty of our approach is to develop a geodatabase of anthropogenic activities derived from historical and archaeological observations to drive our model, and to evaluate our simulations against a new, comprehensive global reconstruction of past land cover. COEVOLVE is organized around three activities: 1) synthesis of observations of past land cover change from paleoecological archives, 2) development of a spatial database of the spread of technology, industry, culture, and trade that influenced global land use and resource consumption patterns and 3) informed by parts 1 and 2, modeling of terrestrial biogeochemical cycles and land surface processes including deforestation, soil erosion, and fire. With a new perspective on preindustrial environmental impact, the COEVOLVE project will make a breakthrough in our understanding of the influence of humans on greenhouse gas concentrations and global climate during the Holocene.

1 500 000 €

Start date: 2013-05-01, End date: 2018-04-30

All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.

1 499 125 €

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

The main objective of this project is to design optical switches with a response time < 5 ps, a switching energy < 1 fJ/bit and compatibility with silicon technology to excel in high-speed data processing at low heat dissipation. This will be pursued by combining the chemistry of inorganic, nanocrystalline colloids and organic semiconductor molecules to fabricate thin films of organic-inorganic hybrid nanostructures. Optical switches play a pivotal role in modern data processing based on silicon photonics, where they control the interface between photonic optical fibers used for data transmission and electronic processing units for computing. Data transfer across this interface is slow compared to that in optical interconnects and high-speed silicon transistors, such that faster optical switching accelerates the overall speed of data processing of the system as a whole. By modifying the surface of the inorganic nanocrystals with conductive molecular linkers and self-assembly into macroscopic solid state materials, new electronic and photonic properties arise due to charge transfer at the organic/inorganic interface. The multiple optical resonances in these hybrid materials result in strong optoelectronic interactions with external light beams, which are exploited for converting photonic into electronic signals at unprecedented speed. A key concept here is an activated absorption mechanism, in which the nanocrystals act as sensitizers with short-lived excited states, which are activated by a first optical pump beam. Efficient charge transfer at the organic/inorganic interface temporarily creates additional resonances in the molecular linkers, which may be probed by a second optical beam for as long as the sensitizer is in its excited state. Utilizing nanocrystals with excited state lifetimes < 5ps will reward ultrafast response times to pave the way for novel optical switches and high-speed data processing rates for silicon photonics.

1 497 375 €

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

Low-rank matrix approximation (LRA) techniques such as principal component analysis (PCA) are powerful tools for the representation and analysis of high dimensional data, and are used in a wide variety of areas such as machine learning, signal and image processing, data mining, and optimization. Without any constraints and using the least squares error, LRA can be solved via the singular value decomposition. However, in practice, this model is often not suitable mainly because (i) the data might be contaminated with outliers, missing data and non-Gaussian noise, and (ii) the low-rank factors of the decomposition might have to satisfy some specific constraints. Hence, in recent years, many variants of LRA have been introduced, using different constraints on the factors and using different objective functions to assess the quality of the approximation; e.g., sparse PCA, PCA with missing data, independent component analysis and nonnegative matrix factorization. Although these new constrained LRA models have become very popular and standard in some fields, there is still a significant gap between theory and practice. In this project, our goal is to reduce this gap by attacking the problem in an integrated way making connections between LRA variants, and by using four very different but complementary perspectives: (1) computational complexity issues, (2) provably correct algorithms, (3) heuristics for difficult instances, and (4) application-oriented aspects. This unified and multi-disciplinary approach will enable us to understand these problems better, to develop and analyze new and existing algorithms and to then use them for applications. Our ultimate goal is to provide practitioners with new tools and to allow them to decide which method to use in which situation and to know what to expect from it.

1 291 750 €

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

Social protection has been one of the most popular instruments for promoting human development across the globe. However, the great majority of the global population is not or only partly covered by social protection. Especially in developing countries it is often the very poorest who do not receive essential social benefits. This is highly problematic since inclusive social protection is assumed to be a key factor for national productivity, global economic growth and domestic stability. Social protection in many developing countries can be traced back to colonial times. Surprisingly, the influence of colonialism has been a blind spot for existing theories and empirical studies of comparative social policy. In this project it is argued that the colonial legacy in terms of the imperial strategy of the colonial power, the characteristics of the colonized society and the interplay between the two is crucial in explaining early and contemporary social protection. Hence, the main objective of this project is to systematically understand how colonialism has shaped the remarkable differences in social protection and its postcolonial outcomes. Given the paucity of our information and understanding of social protection in former colonies, an interactive dataset on the characteristics, origins and outcomes of social protection will be developed including comprehensive data on former British and French colonies from the beginning of the 20th century until today. The dataset will be backed by insights derived from four case studies elucidating the causal mechanisms between the colonial legacy and early and contemporary social protection. The proposed project breaks new ground by improving our understanding of why social protection in some developing countries has led to more inclusive societies while reinforcing existing inequalities in others. Such an understanding is a prerequisite in informing the contemporary struggle against poverty and social inequality.

1 486 250 €

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

We want to use selective laser melting to pattern a substrate with different solid micro particles at a density of 1 million spots per cm2. First, a homogeneous particle layer is deposited on a substrate and a pattern of micro spots of melted matrix is generated by laser radiation. Then, non-melted particles are blown away. Embedded within the particles are different chemically reactive amino acid derivatives that will start coupling to very small synthesis sites upon melting the particle pattern in an oven. This is done once all of the 20 different amino acid particles have been glued by laser patterning to the surface. Washing away uncoupled material, removing Fmoc protecting group, and repeating the patterning steps according to standard Merrifield synthesis, leads to the combinatorial synthesis of very high-density peptide arrays. The main objective of this proposal is to develop this method up to the level of a semi-automated synthesis machine. In addition, we will use the manufactured very high-density peptide arrays to readout the information that is deposited in the immune system, i.e. find a peptide binder for every one of the 200-500 antibody species that patrol the serum of an individual in elevated levels. These experiments might lead to novel tools to find out the causes of hitherto enigmatic diseases because then we might be able to correlate antibody patterns with disease status without knowing in advance the disease-specific antibodies. Beyond the life sciences, we want to embed 10.000 peptides per cm2 within an insulating layer of alkane thiols, each on a different gold pad of a specially designed screening chip. Then, we could readout I/V characteristics of individual peptide species, and eventually find peptide-based diodes. These could be modified in their sequence and screened again for better performance. This evolution-inspired screening approach might lead to novel materials that could be used in fuel cells.

1 494 600 €

Start date: 2011-11-01, End date: 2016-10-31

Cell-to-cell communication is a central aspect for understanding how cells form and organize multi-cellular communities involving progressive cell specialization. Multi-cellularity cell specialization cell communication those keywords are frequently used to distinguish metazoans from bacteria. Yet bacteria can form morphologically complex multi-cellular communities, they can non-genetically diversify and they can communicate. This implies that even prokaryotic networks must possess the properties to facilitate these complex functions. Thus basic network features ( motifs ) determining these functions can be discovered and characterized from studying simpler bacterial networks. We want to focus on communication motifs that are present in the gene-regulatory network of Bacillus subtilis. Our proposed methodology involves a combination of quantitative fluorescence microscopy techniques (QFTLM, FRET), developmental assays, signal transduction studies in controlled micro-environments and information theory to quantitatively characterize communication motifs..

1 496 840 €

Start date: 2011-09-01, End date: 2016-08-31