ERC FUNDED PROJECTS

For over a century it was believed that ammonium could only be oxidized by microbes in the presence of oxygen. The possibility of anaerobic ammonium oxidation (anammox) was considered impossible. However, about 10 years ago the microbes responsible for the anammox reaction were discovered in a wastewater plant. This was followed by the identification of the responsible bacteria. Recently, the widespread environmental occurrence of the anammox bacteria was demonstrated leading to the realization that anammox bacteria may play a major role in biological nitrogen cycling. The anammox bacteria are unique microbes with many unusual properties. These include the biological turn-over of hydrazine, a well known rocket fuel, the biological synthesis of ladderane lipids, and the presence of a prokaryotic organelle in the cytoplasma of anammox bacteria. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the anammox bacteria. Such understanding contributes directly to our environment and economy because the anammox bacteria form a new opportunity for nitrogen removal from wastewater, cheaper, with lower carbon dioxide emissions than existing technology. Scientifically the results will contribute to the understanding how hydrazine and dinitrogen gas are made by the anammox bacteria. The research will show which gene products are responsible for the anammox reaction, and how their expression is regulated. Furthermore, the experiments proposed will show if the prokaryotic organelle in anammox bacteria is involved in energy generation. Together the environmental and metabolic data will help to understand why anammox bacteria are so successful in the biogeochemical nitrogen cycle and thus shape our planets atmosphere. The different research lines will employ state of the art microbial and molecular methods to unravel the exceptional properties of these highly unusual and important anammox bacteria.

2 500 000 €

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

In the 90s, two landmark observations brought to a paradigm shift about the role of astrocytes in brain function: 1) astrocytes respond to signals coming from other cells with transient Ca2+ elevations; 2) Ca2+ transients in astrocytes trigger release of neuroactive and vasoactive agents. Since then, many modulatory astrocytic actions and mechanisms were described, forming a complex - partly contradictory - picture, in which the exact roles and modes of astrocyte action remain ill defined. Our project wants to bring light into the “language of astrocytes”, i.e. into how they communicate with neurons and, ultimately, address their role in brain computations and cognitive behavior. To this end we will perform 4 complementary levels of analysis using highly innovative methodologies in order to obtain unprecedented results. We will study: 1) the subcellular organization of astrocytes underlying local microdomain communications by use of correlative light-electron microscopy; 2) the way individual astrocytes integrate inputs and control synaptic ensembles using 3D two-photon imaging, genetically-encoded Ca2+ indicators, optogenetics and electrophysiology; 3) the contribution of astrocyte ensembles to behavior-relevant circuit operations using miniaturized microscopes capturing neuronal/astrocytic population dynamics in freely-moving mice during memory tests; 4) the contribution of astrocytic signalling mechanisms to cognitive behavior using a set of new mouse lines with conditional, astrocyte-specific genetic modification of signalling pathways. We expect that this combination of groundbreaking ideas, innovative technologies and multilevel analysis makes our project highly attractive to the neuroscience community at large, bridging aspects of molecular, cellular, systems and behavioral neuroscience, with the goal of leading from a provocative hypothesis to the conclusive demonstration of whether and how “the language of astrocytes” participates in memory and cognition.

2 513 896 €

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

Autonomous programmable computing devices made of biological molecules hold the promise of interacting with the biological environment in future biological and medical applications. Our laboratory's long-term objective is to develop a 'Doctor in a cell': molecular-sized device that can roam the body, equipped with medical knowledge. It would diagnose a disease by analyzing the data available in its biochemical environment based on the encoded medical knowledge and treat it by releasing the appropriate drug molecule in situ. This kind of device might, in the future, be delivered to all cells in a specific tissue, organ or the whole organism, and cure or kill only those cells diagnosed with a disease. Our laboratory embarked on the attempt to design and build these molecular computing devices and lay the foundation for their future biomedical applications. Several important milestones have already been accomplished towards the realization of the Doctor in a cell vision. The subject of this proposal is a construction of autonomous biomolecular computers that could be delivered into a living cell, interact with endogenous biomolecules that are known to indicate diseases, logically analyze them, make a diagnostic decision and couple it to the production of an active biomolecule capable of influencing cell fate.

2 125 980 €

Start date: 2009-01-01, End date: 2013-10-31

"The goal of this project is to achieve breakthroughs in a few fundamental questions in 2D statistical physics, using techniques from complex analysis, probability, dynamical systems, geometric measure theory and theoretical physics. Over the last decade, we significantly expanded our understanding of 2D lattice models of statistical physics, their conformally invariant scaling limits and related random geometries. However, there seem to be serious obstacles, preventing further development and requiring novel ideas. We plan to attack those, in particular we intend to: (A) Describe new scaling limits by Schramm’s SLE curves and their generalizations, (B) Study discrete complex structures and use them to describe more 2D models, (C) Describe the scaling limits of random planar graphs by the Liouville Quantum Gravity, (D) Understand universality and lay framework for the Renormalization Group Formalism, (E) Go beyond the current setup of spin models and SLEs. These problems are known to be very difficult, but fundamental questions, which have the potential to lead to significant breakthroughs in our understanding of phase transitions, allowing for further progresses. In resolving them, we plan to exploit interactions of different subjects, and recent advances are encouraging."

1 995 900 €

Start date: 2014-01-01, End date: 2018-12-31

In the last decade, the fields of nanoplasmonics and photonic crystals have opened up the nanoscale for optical control. Both the flow and emission of light can be controlled at these small length scales, giving rise to new science and applications. Interestingly, freely propagating light beams can already contain nanoscale features, i.e. optical singularities. Little is known about this nanoscale structure of light. I propose to (1) reveal the structure of light at the nanoscale and its interaction with geometrical structures or other light structures; and (2) achieve full spatio-temporal control of the nanoscale structure of light. Crucial to achieving these goals are technological innovations, which will be crosscutting objectives. These include the first nonlinear vectorial scanning near-field microscope and novel near-field probes allowing access to new combinations of vector fields. This next step in the field of nano-optics is possible due to recent breakthroughs in the control and visualization of light at the nanoscale obtained in my group. I will combine newly acquired access to the vectorial nature of light with its active control to investigate how (deep-) subwavelength structures of light of different frequencies affect each other when coupled through a nonlinear interaction in a nanostructured material. In parallel I will focus on optical singularities. Because of their extreme size, small changes in their position will lead to huge effects in the local light fields, opening up potential for all-optical and therefore ultrafast control. The research will lead to innovations in the visualization and control of light at the nanoscale, access to the magnetic component of light, nanoscale nonlinear optics and coherent control of light fields. The knowledge gain will be crucial for applications like ultrasensitive biosensors based on superchiral light, ultrafast magneto-optics and nanoscale quantum optics.

2 493 600 €

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

Societies in past and present are regularly confronted with major hazards, which sometimes have disastrous effects. Some societies are successful in preventing these effects and buffering threats, or they recover quickly, while others prove highly vulnerable. Why is this? Increasingly it is clear that disasters are not merely natural events, and also that wealth and technology alone are not adequate to prevent them. Rather, hazards and disasters are social occurrences as well, and they form a tough test for the organizational capacities of a society, both in mitigation and recovery. This project targets a main element of this capacity, namely: the way societies have organized the exchange, allocation and use of resources. It aims to explain why some societies do well in preventing or remedying disasters through these institutional arrangements and others not. In order to do so, this project analyses four key variables: the mix of coordination systems available within that society, its degree of autarky, economic equity and political equality. The recent literature on historical and present-day disasters suggests these factors as possible causes of success or failure of institutional arrangements in their confrontation with hazards, but their discussion remains largely descriptive and they have never been systematically analyzed. This research project offers such a systematic investigation, using rural societies in Western Europe in the period 1300-1800 - with their variety of socio-economic characteristics - as a testing ground. The historical perspective enables us to compare widely differing cases, also over the long run, and to test for the variables chosen, in order to isolate the determining factors in the resilience of different societies. By using the opportunities offered by history in this way, we will increase our insight into the relative performance of societies and gain a better understanding of a critical determinant of human wellbeing.

2 227 326 €

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

The study of consciousness is considered one of the final frontiers in science. After centuries of introspection, philosophy, and psychology it is thought that neuroscience will now answer the age-old questions like who is conscious, when, and what of. This will take more, however, than the current approach of finding the neural correlate of consciousness (NCC). We need a new science of consciousness. What is the problem? Behaviour is considered the gold standard of consciousness: when someone says he is conscious, he is, and when he says not, he isn t. But it is impossible to reliably gauge the presence or absence of conscious sensations from behaviour. We will always conflate consciousness with cognitive functions enabling the report, such as attention, working memory or language. Finding the NCC is doomed to fail. Instead, arguments from neuroscience should be allowed to reshape the definition of consciousness. Behavioural or introspective ideas may be a starting point, but ultimately, neural arguments should be allowed to overrule behavioural evidence. I will show how a new neuro-behavioural definition of consciousness can dissociate consciousness from cognition, explains key features of conscious experience, and allows us to understand consciousness at a much more fundamental level. Experiments in man and monkey will test essential predictions of the new definition of consciousness, using techniques such as intracortical recording, EEG, fMRI and pharmacological intervention, combined with psychophysics, learning paradigms or manipulations of consciousness. If these confirm the idea, the new definition of consciousness should be adopted. This means we are in for a change. The new definition of consciousness will move our notion of mind towards that of brain. The sacred first person perspective on consciousness has to be given up. What we may gain, however, is a much better science of consciousness.

2 344 800 €

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

This proposal seeks support for a research group led by James Heckman of the Geary Institute at University College Dublin to produce an integrated developmental approach to health that studies the origins and the evolution of health inequalities over the lifecourse and across generations, and the role played by cognition, personality, genes, and environments. Major experimental and nonexperimental international datasets will be analyzed. A practical guide to implementing related policy will be produced. We will build a science of human development that draws on, extends, and unites research on the biology and epidemiology of health disparities with medical economics and the economics of skill formation. The goal is to develop an integrated framework to jointly model the economic, social and biological mechanisms that produce the evolution and the intergenerational transmission of health and of the capabilities that foster health. The following tasks will be undertaken: (1) We will quantify the importance of early-life conditions in explaining the existence of health disparities across the lifecourse. (2) We will understand how health inequalities are transmitted across generations. (3) We will assess the health benefits from early childhood interventions. (4) We will examine the role of genes and environments in the aetiology and evolution of disease. (5) We will analyze how health inequalities emerge and evolve across the lifecourse. (6) We will give biological foundations to both our models and the health measures we will use. The proposed research will investigate causal channels for promoting health. It will compare the relative effectiveness of interventions at various stages of the life cycle and the benefits and costs of later remediation if early adversity is not adequately eliminated. It will guide the design of current and prospective experimental and longitudinal studies and policy formulation, and will train young scholars in frontier methods of research

2 505 222 €

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

Discrete Mathematics is a fundamental mathematical discipline as well as an essential component of many mathematical areas, and its study has experienced an impressive growth in recent years. Some of the main reasons for this growth are the broad applications of tools and techniques from extremal and probabilistic combinatorics in the rapid development of theoretical Computer Science, in the spectacular recent results in Additive Number Theory and in the study of basic questions in Information Theory. While in the past many of the basic combinatorial results were obtained mainly by ingenuity and detailed reasoning, the modern theory has grown out of this early stage, and often relies on deep, well developed tools, like the probabilistic method, algebraic, topological and geometric techniques. The work of the principal investigator, partly jointly with several collaborators and students, and partly in individual efforts, has played a significant role in the introduction of powerful algebraic, probabilistic, spectral and geometric techniques that influenced the development of modern combinatorics. In the present project he aims to try and further develop such tools, trying to tackle some basic open problems in Combinatorics, as well as significant questions in Additive Combinatorics, Information Theory, and theoretical Computer Science. Progress on the problems mentioned in this proposal, and the study of related ones, is expected to provide new insights on these problems and to lead to the development of novel fruitful techniques that are likely to be useful in Discrete Mathematics as well as in related areas.

1 061 300 €

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

The world is seasonal and organisms’ adjustment of their seasonal timing to this environmental variation is crucial for their fitness. Climate change is strongly impacting seasonal timing which makes a better understanding of the potential for micro-evolution of timing in natural populations essential. As any phenotypic change ultimately involves changes in the physiological mechanism underlying timing, we need to unravel the genetics of these mechanisms. I will carry out a highly integrated eco-evo-devo project on the causes and consequences of genetic variation in timing of reproduction in great tits (Parus major), an ecological model species for that we recently developed state-of-the-art genomic tools. I will develop a powerful instrument to study this timing mechanism by creating selection lines of early and late reproducing birds using genome-wide, rather than phenotypic, selection. The phenotypic response of selection lines birds will be assessed both in controlled environment aviaries and in birds introduced to the wild. To unravel how selection has altered the birds’ physiology I will measure key components of the physiological mechanism at the central, peripheral and egg production levels. As a unique next step I will then introduce selection line birds into a wild population to assess the fitness of these extreme phenotypes. This will enable me, for the first time, to estimate the selection on timing without confounds, which I will compare with traditional estimates using observational data. Finally, I will integrate genetics, physiology and ecology to hindcast the rate of genetic change in our wild population and validate this rate using DNA sampled over a 20-year period. This innovative project integrates state of the art developments in ecology, genetics and physiology (eco-evo-devo) will set new standards for future studies in other wild species and will be of key importance for our predictions of evolutionary responses to a warming world.

2 495 808 €

Start date: 2014-01-01, End date: 2018-12-31

For over a century it was believed that methane (CH4) could only be oxidized by micro-organisms in the presence of oxygen. The possibility of nitrate-dependent or metal-dependent anaerobic oxidation of CH4 (AOM) was generally dismissed. However, about 6 years ago the microbes responsible for the nitrate-AOM reaction were discovered. This was followed by molecular approaches that resulted in the identification of the responsible Methylomirabilis oxyfera bacteria. Recently, the widespread environmental occurrence of these bacteria was demonstrated leading to the realization that AOM may play a significant role in the CH4 and nitrogen cycles. M. oxyfera is a unique microbe with unusual properties that we only begin to understand: the production of oxygen from NO by a putative NO dismutase and a very unusual polygonal cell shape. Even less is known about metals (Fe3+ or Mn4+) as electron acceptors for AOM. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the M. oxyfera bacteria, and to enrich new metal-dependent AOM microbes. Such understanding contributes directly to our environment and economy because AOM is a new sustainable opportunity for nitrogen removal from wastewater. The results will show how the CH4, nitrogen and iron cycles are connected and may lead to new ways of mitigating methane emission. The biodiversity and contribution of AOM-microbes to the biogeochemical cycles in oxygen-limited ecosystems will be investigated, and new metal-AOM enrichments will be performed. Together the environmental and metabolic data will help to understand how and to what extent AOM-microbes contribute to the biogeochemical cycles and thus shape atmosphere of our planet. The research lines will employ state-of-the- art methods to unravel the exceptional properties of these highly unusual and important microbes. The experiments will be performed in one of the world best equipped laboratories for microbial ecology.

2 500 000 €

Start date: 2014-01-01, End date: 2018-12-31

The aim of EXCHANGE is to achieve a breakthrough in the understanding of magnetism and magnetic phase transitions on the time and length scale of the exchange interaction, the strongest force in magnetism. This will be achieved by developing and applying novel, beyond the state-of-the-art femtosecond X-ray and picosecond THz techniques, in combination with laboratory based ultrafast optical techniques and close interaction with new theoretical developments. Magnetism is essentially a phenomenon of angular momentum and the interpretation of magnetic order is based on the concept of exchange interaction. So far, the understanding of the physics of magnetism, including its dynamics, has only been achieved for systems close to their thermodynamic equilibrium. Magnetism at the length and time scale of the exchange interaction, that is to say, at nanometer length and femtosecond time scales, is completely unknown. Yet, future magnetic data storage aims at Tbit densities switched at THz rates, exactly this regime. Recent developments of a new generation of femtosecond X-ray and picosecond THz free electron lasers create the opportunity, now for the first time, to experimentally visualize the transfer of angular momentum under strongly nonequilibrium conditions and thereby provide a so far inaccessible view to the strongest and most fundamental force in magnetism, the exchange interaction. When successful, this will strongly advance the frontiers of knowledge in the Physics of Magnetism, with a high potential to impact contemporary technologies for recording and processing magnetically stored information.

2 495 180 €

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

We are visual animals. Seeing is our prime means for probing the outside world. Although vision appears effortless, we dedicate about a quarter of our most precious organ to this most prominent of all senses. The primary objective of this research programme is to develop a rigorous new view on how the human brain process visual information. This endeavour is based on two concepts: the methodological issue of necessity and the theoretical framework of cortical networks. In the last decades, electrophysiological and neuroimaging studies have identified more than 40 separate maps in the brain that are selectively tuned to specific visual features, such colour or motion. Brain-behaviour relationships inferred from electrophysiology and functional neuroimaging are per definition correlational. We need neuropsychological research with patients who suffered focal brain damage to show us which brain structures are necessary. Only structures that, when damaged, have a selective detrimental effect on the execution of that function are necessary. Other structures that are activated during the execution of that function are merely involved in associated processes. Having established which brain structures are necessary for a specific function, the proposed research programme will investigate how these necessary maps are linked together. As a theoretical perspective, this programme adopts a critical position towards the “what and where pathways” model of Goodale & Milner, the current gold standard. The model postulates two major pathways, each involving a large number of maps; one for processing visuospatial information for motor programming, and one for visual recognition and memory. I have recently suggested an alternative model in which the maps are thought to be organised in multiple overlapping networks. This research programme entails dedicated imaging experiments and a large-scale, neuropsychological study involving four academic medical centres in the Netherlands.

2 499 139 €

Start date: 2014-07-01, End date: 2020-06-30

The ubiquitous FIC domain catalyzes post-translational modifications (PTMs) of target proteins; i.e. adenylylation (=AMPylation) and, more rarely, uridylylation and phosphocholination. Fic proteins are thought to play critical roles in intrinsic signaling processes of prokaryotes and eukaryotes; however, a subset encoded by bacterial pathogens is translocated via dedicated secretion systems into the cytoplasm of mammalian host cells. Some of these host-targeted Fic proteins modify small GTPases leading to collapse of the actin cytoskeleton and other drastic cellular changes. Recently, we described a large set of functionally diverse homologues in pathogens of the genus Bartonella that are required for their “stealth attack” strategy and persistent course of infection [1, 2]. Our preliminary functional analysis of some of these host-targeted Fic proteins of Bartonella demonstrated adenylylation activity towards novel host targets (e.g. tubulin and vimentin). Moreover, in addition to the canonical adenylylation activity they may also display a competing kinase activity resulting from altered ATP binding to the FIC active site. Finally, we described a conserved mechanism of FIC active site auto- inhibition that is relieved by a single amino acid exchange [1], thus facilitating functional analysis of any Fic protein of interest. Despite this recent progress only a few Fic proteins have been functionally characterized to date; our understanding of the functional plasticity of the FIC domain in mediating diverse target PTMs and their specific roles in infection thus remains limited. In this project, we aim to study the vast repertoire of host-targeted Fic proteins of Bartonella to: 1) identify novel target proteins and types of PTMs; 2) study their physiological consequences and molecular mechanisms of action; and 3) analyze structure-function relationships critical for FIC-mediated PTMs and infer from these data determinants of target specificity, type of PTM and mode of regulation. At the forefront of infection biology research, this project is ground-breaking as (i) we will identify a plethora of novel host target PTMs that are critical for a “stealth attack” infection strategy and thus will open new avenues for investigating fundamental mechanisms of persistent infection; and (ii), we will unveil the molecular basis of the remarkable functional versatility of the structurally conserved FIC domain.

1 699 858 €

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

Since the nineteenth century, the reinforced concrete has been generating a vast specialized litterature everywhere in the world. However, none of it has ever tried to make a first assessment of the evolution of one of the most fundamental element in the processing of the reinforced concrete: the formwork; nor have been reconstructed the various ways of processing the surfaces after removal of the formwork in order to get special effects of polished or rustic surface. Therefore, on the subject of manufacturing of the formworks and processing of the surface, there is a true gap in the studies on reinforced concrete that the research The surfaces of cement and reinforced concrete. A history of the formworks and processing of the surface, 1870-2008 intends to fill. Whether historical or operationnal, this gap lacks not only of the context of the evolution from the nineteenth century, but also of a comprehensive outline of the recent production. The purpose of the research is to provide the most comprehensive documentation and the most significant examples of the international architectural production on the subject of formworks and concrete surfaces within the time span considered. Drawing up the outline of the various types of building and processing of the surfaces will be extraordinarily useful for the historiography of architecture, which will hence have a scientific instrument to evaluate the works in terms of connections between form and material in relation to concrete, as well as for the modern formworks in which the technicial and artistical issues of reinforced concrete processing at sight still remain fundamental. The results of the research will be collected in a book with the caracteristics of an essay, consisting of an important written part and an extremely rich iconographic documentation (project drawings, photographs of building sites and tools, etc.); it will be structured as a synthesis between the technical manual and the historical critical essay.

660 000 €

Start date: 2009-03-01, End date: 2015-02-28

FractFrict is a comprehensive study of the space-time dynamics that lead to the failure of both bulk materials and frictionally bound interfaces. In these systems, failure is precipitated by rapidly moving singular fields at the tips of propagating cracks or crack-like fronts that cause material damage at microscopic scales. These generate damage that is macroscopically reflected as characteristic large-scale, modes of material failure. Thus, the structure of the fields that microscopically drive failure is critically important for an overall understanding of how macroscopic failure occurs. The innovative real-time measurements proposed here will provide fundamental understanding of the form of the singular fields, their modes of regularization and their relation to the resultant macroscopic modes of failure. Encompassing different classes of bulk materials and material interfaces. We aim to: [1] To establish a fundamental understanding of the dynamics of the near-tip singular fields, their regularization modes and how they couple to the macroscopic dynamics in both frictional motion and fracture. [2] To determine the types of singular failure processes in different classes of materials and interfaces (e.g. the brittle to ductile transition in amorphous materials, the role of fast fracture processes in frictional motion). [3] To establish local (microscopic) laws of friction/failure and how they evolve into their macroscopic counterparts [4]. To identify the existence and origins of crack instabilities in bulk and interface failure The insights obtained in this research will enable us to manipulate and/or predict material failure modes. The results of this study will shed considerable new light on fundamental open questions in fields as diverse as material design, tribology and geophysics.

2 265 399 €

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

We consider the dynamics of actions on homogeneous spaces of algebraic groups, We propose to tackle the central open problems in the area, including understanding actions of diagonal groups on homogeneous spaces without an entropy assumption, a related conjecture of Furstenberg about measures on R / Z invariant under multiplication by 2 and 3, and obtaining a quantitative understanding of equidistribution properties of unipotent flows and groups generated by unipotents. This has applications in arithmetic, Diophantine approximations, the spectral theory of homogeneous spaces, mathematical physics, and other fields. Connections to arithmetic combinatorics will be pursued.

1 229 714 €

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

The pioneering framework I propose for the analysis of the foundations of human language – the Grammar of the Body – is inspired by sign language. My main aim is to create a body-based model of linguistic compositionality and to provide clues of its evolutionary origins. Instead of analysing sign language (and language generally) from the perspective of mental categories, the radical approach I introduce here analyses language from the outside in, from the physical articulators of the face, hands, and body in sign language, to the grammatical structures they manifest. This new approach capitalizes on the discovery that gestures of each articulator make a meaningful contribution to the whole corporeal display, and yield a hierarchy from small to large in both body and grammar domains: hands/words > head and face/phrasal intonation > torso/discourse perspective. I hypothesize that the corporeal base of compositionality has deeper evolutionary roots in the emotional face and body displays of humans and our closest living relatives, chimpanzees. The multi-disciplinary methodology I adopt will incorporate linguistic analysis of established and newly emerging sign languages with artistic manipulation of language form, and allow us to trace the origins of the system in emotional displays of both humans and apes. My central goal – determining the basis and structure of compositionality in human language – and the unconventional methodological approaches it exploits combine to make this an extremely ambitious proposal with potentially wide-reaching ramifications in the humanities and social sciences.

2 448 318 €

Start date: 2014-07-01, End date: 2019-06-30

We propose to attack a variety of fundamental open problems in harmonic analysis on $p$-adic and real reductive groups. Specifically we seek solutions to the local Langlands conjectures and various normalization problems of discrete series representations. For $p$-adic groups, affine Hecke algebras are a major technical tool. Our understanding of these algebras with unequal parameters has advanced recently and allows us to address these problems. We will compute the Plancherel measure on the Bernstein components explicitly. Using a new transfer principle of Plancherel measures between Hecke algebras we will combine Bernstein components to form $L$-packets, following earlier work of Reeder in small rank. We start with the tamely ramified case, building on work of Reeder-Debacker. We will also explore these methods for $L$-packets of positive depth, using recent progress due to Yu and others. Furthermore we intend to study non-tempered unitary representations via affine Hecke algebras, extending the work of Barbasch-Moy on the Iwahori spherical unitary dual. As for real reductive groups we intend to address essential questions on the convergence of the Fourier-transform. This theory is widely developed for functions which transform finitely under a maximal compact subgroup. We wish to drop this condition in order to obtain global final statements for various classes of rapidly decreasing functions. We intend to extend our results to certain types of homogeneous spaces, e.g symmetric and multiplicity one spaces. For doing so we will embark to develop a suitable spherical character theory for discrete series representations and solve the corresponding normalization problems. The analytic nature of the Plancherel measure and the correct interpretation thereof is the underlying theme which connects the various parts of this proposal.

1 769 000 €

Start date: 2011-03-01, End date: 2016-02-29

Multiple sclerosis (MS) is a prototypic CD4+ T cell-mediated autoimmune disease that damages the central nervous system. MS affects young adults and women twice as often as men. Neurological deficits cause substantial disability at an early age with high socioeconomic impact. Both a complex genetic trait and environmental factors are involved in MS etiology. Similar to other autoimmune diseases it has been known for almost 40 years that certain HLA-class II genes, in MS the two DR15 alleles DRB1*15:01 and DRB5*01:01, confer by far most of the genetic risk. Despite this clear role remarkably little is known about the functional contribution of these genes to MS pathogenesis, and this holds also true for all other T cell-mediated autoimmune diseases. It is assumed that the DR15 alleles present peptides from organ-specific self-proteins to T cells and select an autoreactive CD4+ T cell repertoire that can be activated by certain environmental triggers. Interestingly, the effects of the three known environmental risk factors in MS, Epstein Barr virus (EBV), low vitamin D3 and smoking, are all amplified by DR15. This core issue of research on autoimmune diseases and also MS, how disease-associated HLA-class II molecules contribute to disease development at the functional level, will be studied with state-of-the-art methodologies and a series of novel approaches. These will include in silico modeling approaches, studies of self-peptides, T cell receptor (TCR) repertoire and HLA-DR/peptide complexes, clonally expanded T cells from MS brain tissue and hypothesis-open methods such as combinatorial chemistry and tissue-derived cDNA libraries to identify target antigens. Finally, translational studies will investigate the relationship between the above aspects and MS disease heterogeneity and explore antigen-specific tolerization in proof-of concept clinical trials in MS.

2 368 068 €

Start date: 2015-01-01, End date: 2019-12-31

With increased life expectancy, there has been a critical growth in the portion of the population that suffers from age-related cognitive decline and dementia. Attempts are therefore being made to find ways to slow brain-aging processes; successful therapies would have a significant impact on the quality of life of individuals, and decrease healthcare expenditures. Aging of the immune system has never been suggested as a factor in memory loss. My group formulated the concept of protective autoimmunity , suggesting a linkage between immunity and self-maintenance in the context of the brain in health and disease. Recently, we showed that T lymphocytes recognizing brain-self antigens have a pivotal role in maintaining hippocampal plasticity, as manifested by reduced neurogenesis and impaired cognitive abilities in T-cell deficient mice. Taken together, our novel observations that T cell immunity contributes to hippocampal plasticity, and the fact that T cell immunity decreases with progressive aging create the basis for the present proposal. We will focus on the following questions: (a) Which aspects of cognition are supported by the immune system- learning, memory or both; (b) whether aging of the immune system is sufficient to induce aging of the brain; (c) whether activation of the immune system is sufficient to reverse age-related cognitive decline; (d) the mechanism underlying the effect of peripheral immunity on brain cognition; and (e) potential therapeutic implications of our findings. Our preliminary results demonstrate that the immune system contributes to spatial memory, and that imposing an immune deficiency is sufficient to cause a reversible memory deficit. These findings give strong reason for optimism that memory loss in the elderly is preventable and perhaps reversible by immune-based therapies; we hope that, in the not too distant future, our studies will enable development of a vaccine to prevent CNS aging and cognitive loss in elderly.

1 650 000 €

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

“JudgingHistories” sets out to examine the epistemic premises innate to universalizing historical experience, by scrutinizing the quest for historical understanding and moral judgment against the backdrop of an emerging global cultural environment, fraught with multiple recollections, while using memories of World War II as the empirical core of the study. The pivotal constellation of research emerges by interfacing a horizontal (West-East) alignment traditionally significant for continental European history with a vertically oriented alignment (North-South) that sheds a colonial and post-colonial perspective on World War II. This constellation tends to lead a posteriori to a realm of conflicting, morally permeated discourses of comparison and analogy, revealing the Holocaust to function as the central event of continental narration, on the one hand, while genocidal atrocities highlight the colonial or post-colonial comprehension, perception and narration, on the other. Methodologically, and in order to offer a fresh and innovative view of the emergence of the specifics of knowledge and meaning in the domain of historical understanding in a globalizing world, while placing the signifying event of the Nazis’ systematic annihilation of the Jews at the heart of the question of universal historical judgment, the project proceeds from the colonial periphery of events, however. This “peripheral”, colonial perspective will in a further seemingly paradoxical turn find itself extended into continental European affairs where it functions to help us comprehend the multiplicity of experiences and the diversity of attendant memories unfolding there. Such a research perspective may epistemologically enable us to reconstruct a universally convincing and valid understanding of a foundational event in European and global history, namely the recollection of World War II, and thus render possible common judgment while re-determining the meaning of “History”.

2 499 260 €

Start date: 2014-06-01, End date: 2019-05-31

The proposal is motivated by the need to incorporate financial realities into macroeconomic models. The objective is to introduce leverage and liquidity in standard dynamic general equilibrium models and analyze their macroeconomic implications. The proposal is divided into two sub-projects and analyzes two different aspects of liquidity. The first deals with leverage and market liquidity in developed financial economies. The second examines the demand for liquid assets by emerging countries and its global implications. In the first sub-project, the proposal breaks new ground in the understanding of the dynamics of risk and in explaining some important features of the recent crisis. The project particularly emphasizes the role of self-fulfilling changes in expectations that can lead to sudden large shifts in risk. This can take the form of a financial panic with a big drop in asset prices. Various extensions will investigate the empirical implications as well as the implications for international capital flows, exchange rates, macroeconomic activity and policy recommendations. In the second sub-project, the objective is to formalize and analyze different degrees of liquidity in international capital flows. The project will innovate in finding ways to model liquidity in dynamic open economy models. This will allow a better understanding of the recent pattern in international capital flows, where less developed countries lend to richer economies. It will also shed light on the evolution of global imbalances before and after the crisis.

2 070 570 €

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

After a decade of new insights into single molecule mechanics, my key interests are now directed towards asking how (a) mechanical forces can alter the structure-function relationship of proteins and (b) whether such force-regulated structural alterations are of physiological significance. Since forces are applied by cells via the transmembrane integrin junctions to the extracellular matrix, my goal is to decipher how the extracellular matrix protein fibronectin, integrins, and cytoplasmic scaffolding proteins that link integrins to the cytoskeleton are functionally regulated by force. Using high performance computational approaches, we will derive with Angstrom precision how their structures are changed when stretched using Molecular (MD) and Steered Molecular Dynamics (SMD). Knowledge how tensile forces alter the structure of proteins is central to develop experimentally testable mechanisms how force might regulate various functions. Experimentally, we will first address how the many different functions of fibronectin are regulated by force. This will involve quantitative studies how the interaction of fibronectin fibers with various serum proteins and growth factors is altered when mechanically strained. Preliminary studies show already that the strain-dependent binding can vary greatly among different serum proteins. We will then investigate whether the stretching and unfolding of extracellular matrix proteins co-regulates cell phenotypes. Finally, understanding the principles of mechanotransduction is not only crucial to gain far deeper insight into how cells work, but new technologies might be derived from these novel insights. Our longer-range goals are thus to develop new technologies that exploit proteins as mechanically regulated switches, from the design and screening of drugs that target mechanically strain proteins, to deriving new design principles how to better engineer tissue scaffolds that exploit mechano-regulated cell-matrix interactions.

2 499 990 €

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

Microbial communities (=microbiota) associated with multicellular organisms play an important role in host nutrition and development. Advances in sequencing technology have revealed an unexpectedly high diversity of microbiota; these advances are not, however, matched by advances in our understanding of the evolutionary factors that structure microbiota. The goal of this proposal is to fill this knowledge gap. Evolutionary models developed for simple host-symbiont relationships have identified a number of factors that shape these relationships: mode of transmission (horizontal versus maternal transmission), host ranges and fitness effects for the host. Together these factors influence the role of selection among hosts and the role of selection within hosts (among microbes), the two levels of selection that are believed to shape host-symbiont coevolution. Here I intend to expand these models to host - microbiota interactions. My objectives are to use next-generation sequencing to conduct a comparative study of bacterial microbiota structure and to combine this work with experiments that explore the underlying evolutionary processes. I will focus on the crustacean family Daphniidae (mainly the genus Daphnia)¿a system ideally suited for studies in the field and laboratory. I will test hypotheses about the evolution of mutualism, virulence, cheating and coevolution, as well as test for the role of mode of transmission and host specificity. The analysis of host-microbiota associations will be conducted for entire microbiota and for stepwise simplified, but biologically meaningful subsets. Testing general models for the evolution of microbiota will have implications far beyond the chosen model system, ranging from ecology and evolution to agricultural sciences and medicine. The proposed study is innovative, significant and risk-taking and will combine skills in evolutionary biology, experimental design, bioinformatics and molecular biology.

2 446 004 €

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

"Economic theory is in a crisis. In our lifetime, we have witnessed revolutions in the field that have enriched economics with new models and concepts: the information revolution in the 70's, the game theory mania in the 80's and to a lesser extent the emergence of models of bounded rationality in the 90's. But it's been a long time since we've seen any exciting developments in economic theory. The first part of the project is methodological. I would like to persuade young researchers that the current style of economic theory is one of the factors behind this stagnation. At the core of this part of the project is a future book discussing the style of modeling in economic theory. My plan is to ""re-write"" a sample of top journals papers and to demonstrate that the ideas in those papers could and should have been presented through much simpler models and in far shorter papers. The above dissatisfaction brings me to the second and more pretentious part of the project. I would like to use my experience in coming up with original models in economic theory in order to construct some truly novel models. I seek a fresh start, to whatever extent that is possible, which would hopefully yield entirely new models based on non-conventional primitives. In particular, I would like to use novel typologies of economic agents. This objective is related to the third part of the project, which is motivated by my recent experimental work. My goal is to find correlations in the behavior of subjects and to use them in defining new ""typologies"" of economic agents. The experiments would involve surveys with large samples (obtained through my pedagogical website gametheory.tau.ac.il and media connections), which are essential for such a task; however, at the same time, I intend to use standard experimental procedures in order to minimize any reservations that might arise regarding my experimental methods."

999 960 €

Start date: 2011-06-01, End date: 2017-05-31

Monocytes are central players in inflammation. Progress in understanding their differentiation in target tissues bears potential to manipulate their activities for therapeutic purposes. Here we propose to study the generation of intestinal macrophages (MΦs) as a paradigm, taking advantage of a unique experimental system to elucidate in vivo monocyte fates. The intestine hosts billions of bacteria that assist food uptake, but also pose a challenge, as we have to tolerate these beneficial commensals, yet rapidly mount immune responses to invading pathogens. Failure to maintain this balance causes inflammatory bowel disorders (IBD). Gut resident MΦs are key players in gut homeostasis and inflammation. Here we will study molecular parameters governing their generation from monocytes, as well as their interactions with the immediate tissue surrounding under pathological conditions. We focus on the molecular mechanisms leading to education of monocytes in small and large intestine using genome wide profiling of gene expression, chromatin state and transcription factor binding of monocytes and MΦs. Secondly, we will investigate epithelial and microflora-derived instructing cues, as well as sensory molecules on the MΦs that drive the education. Thirdly, we will study the impact of MΦs that fail to be trained and their role in the development of inflammation. Finally, we will use the insights gained to develop monocyte manipulation strategies that could aid the future development of IBD therapies. Our experimental system allows to follow the in vivo differentiation of engrafted monocytes, as physiological precursor cells, that acquire in a rapid synchronized development in the gut tissue physiologically relevant fates. Expected include (1) fundamental insight into the acquisition and maintenance of MΦ identities in a complex tissue context, (2) progress in our understanding of gut homeostasis and IBD, and (3) guiding insights for future monocyte-targeted therapy.

2 500 000 €

Start date: 2014-01-01, End date: 2018-12-31

Non-abelian topological states of matter are of great interest in condensed matter physics, both due to their extraordinary fundamental properties and to their possible use for quantum computation. The insensitivity of their topological characteristics to disorder, noise, and interaction with the environment may lead to realization of quantum computers with very long coherence times. The realization of a quantum computer ranks among the foremost outstanding problems in physics, particularly in light of the revolutionary rewards the achievement of this goal promises. The proposed theoretical study is multi-dimensional. On the methodological side the multi-dimensionality is in the breadth of the studies we discuss, ranging all the way from phenomenology to mathematical physics. We will aim at detailed understanding of present and future experimental results. We will analyze experimental setups designed to identify, characterize and manipulate non-abelian states. And we will propose and classify novel non-abelian states. On the concrete side, the multi-dimensionality is literal. The systems we consider include quantum dots, one dimensional quantum wires, two dimensional planar systems, and surfaces of three dimensional systems. Our proposal starts with Majorana fermions in systems where spin-orbit coupling, Zeeman fields and proximity coupling to superconductivity are at play. It continues with “edge anyons”, non-abelian quasiparticles residing on edges of abelian Quantum Hall states. It ends with open issues in the physics of the Quantum Hall Effect. We expect that this study will result in clear schemes for unquestionable experimental identification of Majorana fermions, new predictions for more of their measurable consequences, understanding of the feasibility of fractionalized phases in quantum wires, feasible experimental schemes for realizing and observing edge anyons, steps towards their classification, and better understanding of quantum Hall interferometry.

1 529 107 €

Start date: 2013-10-01, End date: 2018-09-30

We have recently developed a bionanotechnology approach to vaccination (Reddy et al., Nature Biotechnology, 25, 1159-1164, 2007): degradable polymeric nanoparticles are designed that: (i) are so small that they can enter the lymphatic circulation by biophysical means; (ii) are efficiently taken up by a large fraction of dendritic cells (DCs) that are resident in the lymph node that drains the injection site; (iii) activate the complement cascade and provide a potent, yet safe, activation signal to those DCs; and (iv) thereby induce a potent, Th1 adaptive immune response to antigen bound to the nanoparticles, with the generation of both antibodies and cytotoxic T lymphocytes. In the present project, we focus on next-generation bionanotechnology vaccine platforms for vaccination. We propose three technological advances, and we propose to demonstrate those three advances in definitive models in the mouse. Specifically, we propose to (Specific Aim 1) evaluate the current approach of complement-mediated DC activation in breaking tolerance to a chronic viral infection (hepatitis B virus, HBV, targeting hepatitis B virus surface antigen, HBsAg) and to combine complement as a danger signal with other nanoparticle-borne danger signals to develop an effective bionanotechnological platform for therapeutic antiviral vaccination; (Specific Aim 2) to develop a new, ultrasmall nanoparticle implementation suitable for delivery of DNA to lymph node-resident DCs, also activating them, to enable more efficient DNA vaccination; and (Specific Aim 3) to develop an ultrasmall nanoparticle implementation suitable for delivery of DNA to DCs resident within the sublingual mucosa, also activating them, to enable efficient DNA mucosal vaccination. The Specific Aim addressing the oral mucosa will begin with HBsAg, to allow comparison to other routes of administration, and will then proceed to antigens from influenza A.

2 499 425 €

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

Neurons exhibit the most marked size differences and diversity in intrinsic growth rates of any class of cells. How then can a neuron coordinate between biosynthesis rates in the soma and the growth needs of different lengths of axons? The central hypothesis of this proposal is that neurons sense the lengths of the axonal microtubule cytoskeleton on an ongoing basis by bidirectional motor-dependent axon-nucleus communication, and that the oscillating retrograde signal generated by this mechanism provides input for the coordinated regulation of neuronal biosynthesis and axonal growth. We will test this hypothesis in a multidisciplinary work program that will characterize and quantify the link between biosynthesis levels and axon outgrowth rates and identify and validate the roles and functions of key molecules underlying this mechanism. This research program will elucidate how neuronal biosynthesis and axon growth are co-regulated. New mechanistic insights on this fundamental aspect of neuronal cell biology will have far-reaching implications. From the basic science perspective, this work will establish a new modality for encoding spatial information in biological signals, providing a one-dimensional solution to the three-dimensional problem of sensing cell size. Moreover, the proposed mechanism can explain intrinsic limits on regenerative neuronal growth and raises the intriguing possibility of opening new avenues to bypass such limits towards acceleration of axonal growth for effective neural repair.

2 498 040 €

Start date: 2013-10-01, End date: 2018-09-30

This proposal argues that current building modeling tools, including popular BIM (Building Information Modeling) systems, provide a poor, inadequate representation of buildings: they represent only the physical and material characteristics of buildings. Buildings, unlike other products, cannot be understood independently of their context, of their intended use, and of their intended users. This shortcoming hinders the ability of current building models to support evaluations other than those based on physical and material characteristics of the building, such as lighting, energy consumption, and structural stability. In particular, the impact of a building that has not yet been built on the life and activities of its future users—a key element in determining whether or not the proposed building will meet the needs of its intended users—is not afforded by current building models. To afford comprehensive prediction and evaluation of future buildings, we also need to model the purpose and function of the building, and the social, cultural, and economic profile of the people who will use it. Although predicting users' behavior in a built environment and their interaction with the building and with other people is a highly complex task, vast research exists that is devoted to analyzing and explaining human behavior in built environments. Still, due to the shortcomings of building models, this knowledge rarely make into the practice of architectural design, at the time buildings are being designed. The proposed research aims at remedying that shortcoming by developing a more a comprehensive building modeling method, which will include form, function, and use information. A better model will lead to better designed buildings. In an era when the irrevocable impact of the built environment on the cost, quality, and perhaps even possibility of life on earth has been recognized, the need to make every effort to improve the tools used by building designers is self-evident.

1 629 370 €

Start date: 2013-12-01, End date: 2018-11-30

"Liquid-vapor phase transitions and boiling are omnipresent in science and technology, but, as far as basic understanding of the hydrodynamics, these phenomena remain ""terra incognita''. The objective of the proposed work is to achieve a fundamental understanding of the fluid dynamics and heat transfer of the liquid-vapor phase transition - in particular of boiling - both on a micro- and on a macro-scale, through experiments under well-defined and controlled conditions, accompanied by theoretical and numerical modeling. Up to now ""boiling'' has been nearly exclusively an engineering subject. We want to change this and make it a physics subject as we are convinced that boiling involves very interesting and practically relevant physics still in need of understanding. On the micro-scale the planned experiments include nucleation studies of individual and interacting vapor bubbles on superheated, geometrically and chemically micro- and nano-structured surfaces. In the bulk of the flow, nucleation will be achieved through laser heating, through local pressure gradients, and through acoustically triggered vaporization of metastable perfluorcarbon nanodroplets in a superheated liquid. The vapor bubbles will be monitored with ultra-high-speed digital imaging, micro particle velocimetry, infrared thermography, and heat flux measurements. On the theoretical side we will use molecular dynamics simulations and the level-set method. On the macro-scale the focus is on closed boiling turbulent flows, namely Rayleigh-Benard and Taylor-Couette flow. We will measure how the vapor bubble formation affects global quantities such as the heat flux and the angular momentum flux and thus the drag, and local flow properties such as the vapor bubble concentration. The numerical simulations, with one generic code for both geometries, will be based on discrete particle models."

2 108 000 €

Start date: 2011-03-01, End date: 2016-02-29

IIn this program I will demonstrate control of light at length scales well below the free-space wavelength, leading to entirely new fundamental phenomena and important applications. The research program is built on specially engineered metamaterials composed of metal nanostructures that support surface plasmons that are embedded in a dielectric. The program is composed of three strongly related topics: 1) I will experimentally demonstrate an entirely new class of optical metamaterials that posses a refractive index that can be tuned over a very large range: -10 < n < +10. Based on coupled plasmonic waveguides, these materials will, for the first time, show true left-handed behaviour of light (n < 0) in the UV/blue spectral range. I will demonstrate negative refraction of light and use these materials to demonstrate the “perfect lens” which enables sub-wavelength imaging of (biological) nanostructures. 2) I will use plasmonic metamaterials to engineer the flow of light in thin-film solar cells. By controlling the scattering and trapping of light using plasmonic nanostructures integrated with semiconductor waveguide slabs I will demonstrate ultra-thin solar cells with efficient collection and conversion of infrared light, aiming at beating the ergodic light trapping limit. 3) I will demonstrate strong coupling between light and mechanical motion in the smallest possible volume. Light trapped in plasmonic metamaterials exerts a force that can lead to a shift in the plasmonic resonance frequency which in turn provides feedback on the mechanical motion. We will use this nanoscale coupling mechanism to actively cool and heat mechanical motion in plasmonic nanostructures and use this phenomenon in a new type of plasmon-based quartz oscillator.

2 286 000 €

Start date: 2011-07-01, End date: 2016-06-30

Emotion is a prime example of the complexity of human mind and behaviour, a psychobiological mechanism shaped by language and culture, which has puzzled scholars in the humanities and social sciences over the centuries. In an effort to reconcile conflicting theoretical traditions, we advocate a componential approach which treats event appraisal, motivational shifts, physiological responses, motor expression, and subjective feeling as dynamically interrelated and integrated components during emotion episodes. Using a prediction-generating theoretical model, we will address both production (elicitation and reaction patterns) and perception (observer inference of emotion from expressive cues). Key issues are the cognitive architecture and mental chronometry of appraisal, neurophysiological structures of relevance and valence detection, the emergence of conscious feelings due to the synchronization of brain/body systems, the generating mechanism for motor expression, the dimensionality of affective space, and the role of embodiment and empathy in perceiving and interpreting emotional expressions. Using multiple paradigms in laboratory, game, simulation, virtual reality, and field settings, we will critically test theory-driven hypotheses by examining brain structures and circuits (via neuroimagery), behaviour (via monitoring decisions and actions), psychophysiological responses (via electrographic recording), facial, vocal, and bodily expressions (via micro-coding and image processing), and conscious feeling (via advanced self-report procedures). In this endeavour, we benefit from extensive research experience, access to outstanding infrastructure, advanced analysis and synthesis methods, validated experimental paradigms as well as, most importantly, from the joint competence of an interdisciplinary affective science group involving philosophers, linguists, psychologists, neuroscientists, behavioural economists, anthropologists, and computer scientists.

2 371 331 €

Start date: 2009-03-01, End date: 2015-02-28

Spins in nanostructures have emerged as a new paradigm for studying quantum optical phenomena in the solid-state. Motivated by potential applications in quantum information processing, the research in this field has focused on isolating a single confined spin from its environment and implementing coherent manipulation. On the other hand, it has been realized that the principal decoherence mechanisms for confined spins, stemming from interactions with nuclear or electron spin reservoirs, are intimately linked to fascinating many-body condensed-matter physics. We propose to use quantum optical techniques to investigate physics of nanostructures in two opposite but equally interesting regimes, where reservoir couplings are either suppressed to facilitate coherent control or enhanced to promote many body effects. The principal focus of our investigation of many-body phenomena will be on the first observation of optical signatures of the Kondo effect arising from exchange coupling between a confined spin and an electron spin reservoir. In addition, we propose to study nonequilibrium dynamics of quantum dot nuclear spins as well as strongly correlated system of interacting polaritons in coupled nano-cavities. To minimize spin decoherence and to implement quantum control, we propose to use nano-cavity assisted optical manipulation of two-electron spin states in double quantum dots; thanks to its resilience against spin decoherence, this system should allow us to realize elementary quantum information tasks such as spin-polarization conversion and spin entanglement. In addition to indium/gallium arsenide based structures, we propose to study semiconducting carbon nanotubes where hyperfine interactions that lead to spin decoherence can be avoided. Our nanotube experiments will focus on understanding the elementary quantum optical properties, with the ultimate goal of demonstrating coherent optical spin manipulation.

2 300 000 €

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

The study of Ancient Israel s (hereafter AI) texts (the Hebrew Bible), material culture and history has been a keystone of European scholarship since the Enlightenment. Biblical exegesis and archaeology contributed impressively to our understanding of AI, yet in certain areas conventional research has reached a stalemate. With very few real-time historical records, with the biblical testimony written a long time after the events described (if not mythical) took place, and with the theological agenda of both the original authors and some modern scholars, reconstructing the world of AI is a complex matter. The exact and life sciences are not restricted by these preconceptions and are able to reveal data not visible to the naked eye. Advances made in the last decade in archaeological science show that this is the wave of the future. The novelty in this proposal is to deploy an arsenal of 10 research tracks from the exact and life sciences in order to better understand AI: A. The time of AI: A1. Radiocarbon: correlating the chronology of AI with neighboring lands. B. The genesis of AI: B1. Human genetics and paleodiet. B2. Geo-archaeology: tracking the subsistence economy of AI. B3. Palynology: relating paleoclimate to settlement oscillations. C. The life of AI: C1. Ceramic petrography: reconstructing trade patterns. C2. Metallurgy: tracking technological advances. D. The mind of AI: D1. Daily mathematics of dimensions: pottery and architecture. D2. Epigraphy: the use of advanced computational methodologies (e.g., artificial intelligence algorithms) in the study of writing in Israel and Judah. E. The identity of AI: E1. Residue analysis of pottery vessels, and- E2. Archaeo-zoology; both aim at elucidating diet, foodways and possibly identity boundaries. This project has the potential to revolutionize the study of AI. Such a broad research plan in the realm of archaeology and the sciences, focused on a single period/theme, has never been conducted anywhere.

2 976 188 €

Start date: 2009-02-01, End date: 2014-01-31

The study of parasitism is important for human welfare but also addresses basic scientific questions cutting across biological disciplines. Traditionally, studies of host-parasite interactions have used various scenarios of how genotypes of the two parties interact based on well-developed theory. Yet, one of the most striking observations is the huge variation in resistance systems across organisms. We lack an appreciation of the diversity of these resistance systems and how they affect, in turn, the parasites. Here, it is proposed to investigate the hypothesis that variation in gene expression is a key element that defines an alternative, flexible and highly adaptable resistance system. The project attempts to unify genomic studies of defence mechanisms with questions of evolutionary ecology of host-parasite interactions. Therefore, the study focuses on an ecologically well-studied system of hosts (Bombus spp.) and their prevalent trypanosome infections (Crithidia). In this system, a highly genetically polymorphic parasite is kept in check by a host with seemingly conserved immune effectors (e.g. anti-microbial peptides, AMPs). Their expression varies depending on the host-parasite pairing, suggesting that variation of the synergistic mixture of expressed defence elements might be crucial and could affect parasite population structure in turn. In the project, experiments and cutting-edge molecular methods will be applied to a natural host-parasite system.

2 100 000 €

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

I propose an extensive and ambitious program to greatly increase our understanding of the properties of amorphous solids, focusing mainly on the mechanical and magnetic properties of these fascinating materials, including their modes of failure via plastic flow, shear banding and fracture. Amorphous solids are important in many modern engineering applications, including as important examples structural glasses, metallic glasses and polymeric glasses. Our work combines a careful analysis of computer simulations of model-glasses with analytic theory in which we introduce to material science methods from statistical and nonlinear physics, both of which are subjects of expertise in our group. We challenge some present approaches that try to connect linear elasticity with some objects that carry plasticity; we claim that nonlinear elasticity is crucial, as its signature appears much before plastic failure. Similarly, we break away from current theories that assume that plastic events are spatially localized. We show that in athermal conditions the opposite is true, and we discover very interesting sub-extensive scaling phenomena characterized by a host of scaling exponents that need to be understood. The peculiarities of amorphous solids, in particular their memory of past deformation, call for the identification of new 'order parameters' that are sorely missing in present theories. Understanding the dependence on system size, temperature, external loading rates etc. calls for introducing new approaches and methods from statistical and nonlinear physics. In the body of the proposal we present a number of preliminary results that point towards a radically new way of thinking that we propose to develop to a new theory over the next five years.

1 792 858 €

Start date: 2011-04-01, End date: 2016-03-31

Economic and demographic trends are impelling the need for a sustainable European workforce, consisting of productive, satisfied employees (micro level), profitable organizations and cohesive workplaces (meso level) and a high employment rate and flourishing economy (macro level). So far comparative research has focused on the micro and macro level. Little is known about the role of organizations and their investments in a sustainable workforce. This groundbreaking research program introduces the organizational level and its interaction with the country and employee levels into research on the sustainable workforce. First, it examines organizational investments in (1) human and social capital, (2) work-life policies, (3) work flexibility, (4) long-term employability of older workers, and (5) flexicurity. Second, it explains differences in such investments and their utilization by employees based on micro, meso and macro characteristics, including interactions between the three levels. Third, it analyzes whether organizational investments contribute to better performance by the employee, the organization and the country. Revising theoretical mechanisms, we formulate original hypotheses based on the idea that interdependencies and norms between organizations and employees influence investments and their utilization by employees. A unique feature of this ambitious program is its multi-level design. Data will be gathered on 30 organizations and their employees in nine countries (Bulgaria, Finland, Germany, Hungary, Netherlands, Portugal, Spain, Sweden, UK) representing different types of welfare regime with ample variation in macro-level conditions. The applicant’s longstanding data-gathering experience and cooperation with researchers in these countries makes data collection feasible. The data will permit in-depth examination of all levels and of micro-meso relationships. The European Foundation’s European Company Survey will be used to test meso-macro hypotheses.

2 250 949 €

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

The project aims to break new ground in syntax and acquisition by combining three main strands of research: 1. The cartography of syntactic structures, which attempts to draw detailed maps of syntactic configurations. 2. The theory of syntactic locality, with special reference to intervention and delimitation principles. 3. The minimalist investigation of the fundamental ingredients of syntactic computations. Interconnected issues of cartography and locality will be addressed both in the adult grammar, and in language acquisition. There is much to expect from a close integration of these domains, which can complement and strengthen each other in substantive ways. The acquisition component introduces important variations on the theoretical themes, thus crucially enriching the empirical basis of the theoretical component; reciprocally, the solid theoretical structure of the project will offer new explanatory dimensions and generate novel research questions for acquisition studies. The “complementizer system” is one privileged locus where cartography and locality meet, as much of the movement action targets this zone of the syntactic tree. The research will then primarily focus on this area. The project aims at opening new paths in i. The “further explanation” of cartographic sequences and delimitation effects; ii. The development of a full-fledged theory of syntactic movement, integrating cartographic studies with minimalist syntax; iii. The exploration of a unified approach to intervention and impenetrability locality principles; iv. An integrated study of locality in adults and children, v. The study of the acquisition of cartographic structures.

2 499 318 €

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

DNA introduced into a cell usually integrates, if at all, at random in the genome. In order for gene targeting to take place, a small vector must scan a huge genome that is packaged in chromatin, identify and bind the target, and engage in strand exchange. This formidable task is likely to be rate limiting. Our goal is to study the process of genome scanning by the vector, to track it from the time of transformation through genome integration and to assist the vector to identify the homologous target. Our tools are particle imaging and tracking, molecular analysis of integration events, and manipulation of the integration process through protein recognition chemistry. Two main approaches will be used to assist homologous integration: first, by protein bridging (proteins that would bind both target and vector), and second by chromatin remodeling. Second, we propose to analyze the connection between chromatin structure and DNA integration. We will analyze how nucleosome positioning affects patterns of DNA integration. In addition, we will stimulate chromatin remodeling in an attempt to facilitate target invasion by the incoming vector. Parallel assays will be built upon fluorescence and genetic markers to correlate between the mode of search and integration per se. The interdisciplinary use of biophysics, genetics, and computational tools opens the prospect to better understand and manipulate the fundamental mechanisms involved in DNA mobility, plant transformation, and gene targeting.

1 958 408 €

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

Activity-based analysis and modelling has rapidly gained momentum in transportation, urban planning, and geography. It examines which activities are conducted where, when, for how long, with whom, and the transport mode and route involved at a very fine scale of spatial and temporal resolution. All currently operational models are concerned with daily activity-travel patterns and do not consider any dynamics, illustrating the limitations of current approaches. This proposal reflects the ambition to achieve breakthroughs in the analysis and modelling of DYNAMIC activity-travel patterns, integrating long-term, mid-term and short-term time horizons: the research agenda in this field of research for the next decade. Several PhD projects will analyze and model the impact of innovative policies concerned with urban futures (focusing on new urban forms, creative pricing policies, restricted energy, community-based social networks and personalized guidance systems) on behavioural change in activity-travel patterns. Results will be integrated into a new generation multi-agent activity-based system to simulate primary and secondary effects of various types of policies on dynamic activity-travel patterns and therefore on accessibility, mobility, time use, energy consumption, social exclusion, and economic welfare. A large scale panel survey of dynamic activity-travel patterns (supposed to be the first of its kind in the world), and (virtual reality) adaptation experiments will be used for the analyses and estimating and validating the models. The project will lead to (i) a better understanding and an integrative framework and simulation model to assess the primary and secondary effects of various types of policies on sustainable urban environments in terms of a series of indicators (mobility, accessibility, energy use, etc.), derived from dynamics activity-travel patterns and (ii) guidelines how the effectiveness of such policies can be improved.

2 461 681 €

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

Viruses are simple, obligatory, intracellular parasites that depend on the host cell for most of the steps in the replication cycle. Not only do they rely on the cells biosynthetic machinery, they exploit cellular processes for signaling, membrane trafficking, intra-cellular transport, nuclear import and export, molecular sorting, transcriptional regulation, etc. To access the full spectrum of host cell functions in the infection of three different viruses in an unbiased and systematic fashion, we will identify the critical host cell proteins needed by monitoring infection in human tissue culture cells after silencing individual genes using genome-wide siRNA libraries and large sub-libraries based on the human genome. The three viruses are vaccinia virus (a poxvirus), human papilloma virus 16, and Uukuniemi virus (a bunyavirus). They are members of important but poorly analyzed pathogen families representing enveloped and nonenveloped viruses, RNA and DNA viruses, viruses that replicate in the nucleus and in the cytosol. The infection assays to be used are fully automated, and make use of high-content microscopic read-outs for infection and virus production. Identification of the viral infectomes , in this way, offers a valuable, new perspective into the complexities of the infection process, and opens wide new areas of basic and applied research. After validation of hits , extensive biochemical and cell biological analysis will be performed on a selected set of host proteins and pathways identified through the infectome analysis. We will determine which steps in the replication cycle are affected, which mechanisms are involved, and which cellular pathways play a role. For detailed analysis, we will focus on mechanisms in entry, uncoating, and early intracellular events. A large spectrum of techniques including live cell imaging and single particle tracking will be used to follow up the screening results with functional and mechanistic studies.

2 498 400 €

Start date: 2009-02-01, End date: 2014-01-31