ERC FUNDED PROJECTS

Cognition improves an animal’s ability to tune its responses to environmental conditions. In group living animals, communication works to form a collective cognition that expands the group’s abilities beyond those of individuals. Despite much research, to date, there is little understanding of how collective cognition emerges within biological ensembles. A major obstacle towards such an understanding is the rarity of comprehensive multi-scale empirical data of these complex systems. We have demonstrated cooperative load transport by ants to be an ideal system to study the emergence of cognition. Similar to other complex cognitive systems, the ants employ high levels of emergence to achieve efficient problem solving over a large range of scenarios. Unique to this system, is its extreme amenability to experimental measurement and manipulation where internal conflicts map to forces, abstract decision making is reflected in direction changes, and future planning manifested in pheromone trails. This allows for an unprecedentedly detailed, multi-scale empirical description of the moment-to-moment unfolding of sophisticated cognitive processes. This proposal is aimed at materializing this potential to the full. We will examine the ants’ problem solving capabilities under a variety of environmental challenges. We will expose the underpinning rules on the different organizational scales, the flow of information between them, and their relative contributions to collective performance. This will allow for empirical comparisons between the ‘group’ and the ‘sum of its parts’ from which we will quantify the level of emergence in this system. Using the language of information, we will map the boundaries of this group’s collective cognition and relate them to the range of habitable environmental niches. Moreover, we will generalize these insights to formulate a new paradigm of emergence in biological groups opening new horizons in the study of cognitive processes in general.

2 000 000 €

Start date: 2018-06-01, End date: 2023-05-31

Main goal. We aim to understand the puzzling coexistence of antibiotic-resistant and antibiotic-sensitive species in natural soil environments, using novel quantitative experimental techniques and mathematical analysis. The ecological insights gained will be translated into novel treatment strategies for combating antibiotic resistance. Background. Microbial soil ecosystems comprise communities of species interacting through copious secretion of antibiotics and other chemicals. Defence mechanisms, i.e. resistance to antibiotics, are ubiquitous in these wild communities. However, in sharp contrast to clinical settings, resistance does not take over the population. Our hypothesis is that the ecological setting provides natural mechanisms that keep antibiotic resistance in check. We are motivated by our recent finding that specific antibiotic combinations can generate selection against resistance and that soil microbial strains produce compounds that directly target antibiotic resistant mechanisms. Approaches. We will: (1) Isolate natural bacterial species from individual grains of soil, characterize their ability to produce and resist antibiotics and identify the spatial scale for correlations between resistance and production. (2) Systematically measure interactions between species and identify interaction patterns enriched in co-existing communities derived from the same grain of soil. (3) Introducing fluorescently-labelled resistant and sensitive strains into natural soil, we will measure the fitness cost and benefit of antibiotic resistance in situ and identify natural compounds that select against resistance. (4) Test whether such “selection-inverting” compounds can slow evolution of resistance to antibiotics in continuous culture experiments. Conclusions. These findings will provide insights into the ecological processes that keep antibiotic resistance in check, and will suggest novel antimicrobial treatment strategies.

1 900 000 €

Start date: 2012-09-01, End date: 2018-08-31

Bacteria in nature exhibit remarkable capacity to sense their surroundings and rapidly adapt to diverse conditions by gaining new beneficial traits. This extraordinary feature facilitates their survival when facing extreme environments. Utilizing Bacillus subtilis as our primary model organism, we propose to study two facets of this vital bacterial attribute: communication via extracellular nanotubes, and persistence as resilient spores while maintaining the potential to revive. Exploring these fascinating aspects of bacterial physiology is likely to change our view as to how bacteria sense, respond, endure and communicate with their extracellular environment. We have recently discovered a previously uncharacterized mode of bacterial communication, mediated by tubular extensions (nanotubes) that bridge neighboring cells, providing a route for exchange of intracellular molecules. Nanotube-mediated molecular sharing may represent a key form of bacterial communication in nature, allowing for the emergence of new phenotypes and increasing survival in fluctuating environments. Here we propose to develop strategies for observing nanotube formation and molecular exchange in living bacterial cells, and to characterize the molecular composition of nanotubes. We will explore the premise that nanotubes serve as a strategy to expand the cell surface, and will determine whether nanotubes provide a conduit for phage infection and spreading. Furthermore, the formation and functionality of interspecies nanotubes will be explored. An additional mode employed by bacteria to achieve extreme robustness is the ability to reside as long lasting spores. Previously held views considered the spore to be dormant and metabolically inert. However, we have recently shown that at least one week following spore formation, during an adaptive period, the spore senses and responds to environmental cues and undergoes corresponding molecular changes, influencing subsequent emergence from quiescence.

1 497 800 €

Start date: 2014-04-01, End date: 2019-03-31

Although various aspects of biomineralisation in corals have been studied for decades, the basic mechanism of precipitation of the aragonite skeleton remains enigmatic. Two parallel lines of inquiry have emerged: geochemist models of calcification that are directly related to seawater carbonate chemistry at thermodynamic equilibrium. Here, the role of the organisms in the precipitation reaction is largely ignored. The second line is based on biological considerations of the biomineralisation process, which focuses on models of biophysical processes far from thermodynamic equilibrium that concentrate calcium ions, anions and proteins responsible for nucleation in specific compartments. Recently, I identified and cloned a group of highly acidic proteins derived the common stony coral, Stylophora pistillata. All of the cloned proteins precipitate aragonite in seawater at pH 8.2 and 7.6 in-vitro. However, it is not at all clear if the expression of these proteins in-vivo is sufficient for the formation of an aragonite skeleton at seawater pH values below ~7.8. Here using a combination of molecular, biophysical, genomic, and cell biological approaches, we proposed to test the core hypothesis that, unless wounded or otherwise having skeletal material exposed directly to seawater, stony zooxanthellate corals will continue to calcify at pH values projected for the CO2 emissions scenarios for 2100. Specifically, the objectives of Ca2Coral are to: 1) Use functional genomics to identify the key genes and proteins involved both in the organic matrix and skeleton formation in the adult holobiont and during its larval development. 2) Use a genetics approach to elucidate the roles of specific proteins in the biomineralisation process. 3) Use ultra-high resolution imaging and spectroscopic analysis at different pH levels to elucidate the biomineralisation pathways and mineral precursor in corals in the adult holobiont and during its larval development.

1 499 741 €

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

Social-science explanations for rising wage inequality have reached a dead end. Most economists argue that computerization has been primarily responsible, while on the other side of the argument are sociologists and political scientists who stress the role of political forces in the evolution process of wages. I would like to use my knowledge and experience to come up with an original theory on the complex dynamics between technology and politics in order to solve two unsettled questions regarding the role of computerization in rising wage inequality: First, how can computerization, which diffused simultaneously in rich countries, explain the divergent inequality trends in Europe and the United States? Second, what are the mechanisms behind the well-known observed positive correlation between computers and earnings? To answer the first question, I develop a new institutional agenda stating that politics, broadly defined, mitigates the effects of technological change on wages by stimulating norms of fair pay and equity. To answer the second question, I propose a truly novel perspective that conceptualizes the earnings advantage that derives from computerization around access to and control of information on the production process. Capitalizing on this new perspective, I develop a new approach to measuring computerization to capture the form of workers’ interaction with computers at work, and build a research strategy for analysing the effect of computerization on wages across countries and workplaces, and over time. This research project challenges the common understanding of technology’s role in producing economic inequality, and would thereby significantly impact all of the abovementioned disciplines, which are debating over the upswing in wage inequality, as well as public policy, which discusses what should be done to confront the resurgence of income inequality.

1 495 091 €

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

Most bacterial pathogens are lysogens, namely carry DNA of active phages within their genome, referred to as prophages. While these prophages have the potential to turn under stress into infective viruses which kill their host bacterium in a matter of minutes, it is unclear how pathogens manage to survive this internal threat under the stresses imposed by their invasion into mammalian cells. In the proposed project, we will study the hypothesis that a complex bacteria-phage cooperative adaptation supports virulence during mammalian infection while preventing inadvertent killing by phages. Several years ago, we uncovered a novel pathogen-phage interaction, in which an infective prophage promotes the virulence of its host, the bacterial pathogen Listeria monocytogenes (Lm), via adaptive behaviour. More recently, we discovered that the prophage, though fully infective, is non-autonomous- completely dependent on regulatory factors derived from inactive prophage remnants that reside in the Lm chromosome. These findings lead us to propose that the intimate cross-regulatory interactions between all phage elements within the genome (infective and remnant), are crucial in promoting bacteria-phage patho-adaptive behaviours in the mammalian niche and thereby bacterial virulence. In the proposed project, we will investigate specific cross-regulatory and cooperative mechanisms of all the phage elements, study the domestication of phage remnant-derived regulatory factors, and examine the hypothesis that they collectively form an auxiliary phage-control system that tempers infective phages. Finally, we will examine the premise that the mammalian niche drives the evolution of temperate phages into patho-adaptive phages, and that phages that lack this adaptation may kill host pathogens during infection. This work is expected to provide novel insights into bacteria-phage coexistence in mammalian environments and to facilitate the development of innovative phage therapy strategies.

2 200 000 €

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

CRISPR-Cas systems are microbial defense systems that provide prokaryotes with acquired and heritable DNA-based immunity against selfish genetic elements, primarily viruses. However, the full scope of benefits that these systems can provide, as well as their costs remain unknown. Specifically, it is unclear whether the benefits against viral infection outweigh the continual costs incurred even in the absence of parasitic elements, and whether CRISPR-Cas systems affect microbial genome diversity in nature. Since CRISPR-Cas systems can impede lateral gene transfer, it is often assumed that they reduce genetic diversity. Conversely, our recent results suggest the exact opposite: that these systems generate a high level of genomic diversity within populations. We have recently combined genomics of environmental strains and experimental genetics to show that archaea frequently acquire CRISPR immune memory, known as spacers, from chromosomes of related species in the environment. The presence of these spacers reduces gene exchange between lineages, indicating that CRISPR-Cas contributes to diversification. We have also shown that such inter-species mating events induce the acquisition of spacers against a strain's own replicons, supporting a role for CRISPR-Cas systems in generating deletions in natural plasmids and unessential genomic loci, again increasing genome diversity within populations. Here we aim to test our hypothesis that CRISPR-Cas systems increase within-population diversity, and quantify their benefits to both cells and populations, using large-scale genomics and experimental evolution. We will explore how these systems alter the patterns of recombination within and between species, and explore the potential involvement of CRISPR-associated proteins in cellular DNA repair. This work will reveal the eco-evolutionary role of CRISPR-Cas systems in shaping microbial populations, and open new research avenues regarding additional roles beyond anti-viral defense

2 495 625 €

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

Bacterial pathogens remain a significant threat to global health, necessitating a better understanding of host-pathogen biology. While various evidence point to early infection as a key event in the eventual progression to disease, our recent preliminary data show that during this stage, highly adaptable and dynamic host cells and bacteria engage in complex, diverse interactions that contribute to well-documented heterogeneous outcomes of infection. However, current methodologies rely on measurements of bulk populations, thereby overlooking this diversity that can trigger different outcomes. This application focuses on understanding heterogeneity during the first stages of infection in order to reduce the complexity of these interactions into informative readouts of population physiology and predictors of infection outcome. We will apply multiparametric single-cell analysis to obtain an accurate and complete description of infection with the enteric intracellular pathogen Salmonella of macrophages in vitro, and in early stages of mice colonization. We will characterize the molecular details that underlie distinct infection outcomes of individual encounters, to reconstruct the repertoire of host and pathogen strategies that prevail at critical stages of early infection. We propose the following three objectives: (1) Develop methodologies to simultaneously profile host and pathogen transcriptional changes on a single cell level; 2) Characterizing the molecular details that underlie the formation of subpopulations during macrophage infection; and (3) Determine how host and pathogen encounters in vivo result in emergence of specialized subpopulations, recruitment of immune cells and pathogen dissemination. We anticipate that this work will fundamentally shift our paradigms of infectious disease pathogenesis and lay the groundwork for the development of a new generation of therapeutic agents targeting the specific host-pathogen interactions ultimately driving disease.

1 499 999 €

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

The goal of this research initiative is to construct large-scale computational modeling of how knowledge of the world emerges from the combination of innate mechanisms and visual experience. The ultimate goal is a ‘digital baby’ model which, through perception and interaction with the world, develops on its own representations of complex concepts that allow it to understand the world around it, in terms of objects, object categories, events, agents, actions, goals, social interactions, etc. A wealth of empirical research in the cognitive sciences have studied how natural concepts in these domains are acquired spontaneously and efficiently from perceptual experience, but a major open challenge is an understating of the processes and computations involved by rigorous testable models. To deal with this challenge we propose a novel methodology based on two components. The first, ‘computational Nativism’, is a computational theory of cognitively and biologically plausible innate structures , which guide the system along specific paths through its acquisition of knowledge, to continuously acquire meaningful concepts, which can be significant to the observer, but statistically inconspicuous in the sensory input. The second, ‘embedded interpretation’ is a new way of acquiring extended learning and interpretation processes. This is obtained by placing perceptual inference mechanisms within a broader perception-action loop, where the actions in the loop are not overt actions, but internal operation over internal representation. The results will provide new modeling and understanding of the age-old problem of how innate mechanisms and perception are combined in human cognition, and may lay foundation for a major research direction dealing with computational cognitive development.

1 647 175 €

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

The asset management industry is a 60 trillion euros industry world wide, with a ratio of assets under management by asset managers to GDP around 100 percent. Despite the prominence of financial intermediaries in financial markets, our understanding of the portfolio delegation relationship, and its equilibrium asset pricing and contracting implications is at its infancy. The recent financial crisis has further underscored the importance of better understanding the incentives of financial intermediaries, the distortions induced by these incentives, the contracts that can help mitigate these distortions, and the impact of their trading on asset pricing dynamics. One key feature that is at the core of the asset management relationship is its dynamic nature: investors can, and do, periodically re-allocate funds between managers and between funds and other investment vehicles. The magnitude of fund flows, both over time and accross funds at a given point in time, have been shown to be quantitatively large relative to assets under management. The ability of investors to quickly pull money out of funds at a time of crisis can have significant ramifications for the stability of the financial system. Understanding implications of the dynamic nature of the delegation relationship is imperative in order to understand multiple aspects related to delegation and financial markets at large, including: risk taking behavior by funds; welfare implications for investors who invest in funds; what regulatory restrictions should be imposed on contracts; the evolution, past and future, of the asset management industry; securities return dynamics. The objective is to develope models that will incorporate dynamic flows in settings that will allow studying implications and deriving empirical predictions on multiple dimensions: portfolio choice; optimal contracting; distribution of assets across funds; equilibrium asset pricing dynamics.

728 436 €

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

The vast majority of published research on the impact of school interventions has examined their effects on short-run outcomes, primarily test scores. While important, a possibly deeper question of interest to society is the impact of such interventions on long-run life outcomes. This is a critical question because the ultimate goal of education is to improve lifetime well-being. Recent research has begun to look at this issue but much work remains to be done, particularly with regard to the long-term effects of interventions explicitly targeting improvement in general quality and students’ educational attainment. This proposal examines the impact of seven different schooling interventions – teachers’ quality, school quality, remedial education, school choice, teacher incentive payments, students' conditional cash transfers and an experiment with an increase in the return to schooling – on long-run life outcomes, including educational attainment, employment, income, marriage and fertility, crime and welfare dependency. To address this important question I will exploit unique data from seven experimental programs and natural experiments implemented simultaneously at different schools in Israel. All programs were successful in achieving their short-term objectives, though the cost of the programs varied. This undertaking presents a unique context with unusual data and very compelling empirical settings. I will examine whether these programs also achieved a longer-term measure of success by improving students’ life outcomes. Another unique feature of the proposed study is that the interventions vary widely and touch on some emergent educational trends. The body of empirical evidence from this study will provide a more complete picture of the individual and social returns from these educational interventions, and will allow policymakers to make more informed decisions when deciding which educational programs lead to the most beneficial use of limited school resources.

1 519 000 €

Start date: 2013-05-01, End date: 2019-04-30

Intractable conflicts are one of the gravest challenges to both humanity and science. These conflicts are initiated and perpetuated by people; therefore changing people's hearts and minds constitutes a huge step towards resolution. Research on emotions in conflicts has led to the realization that intergroup emotions are critical to conflict dynamics. This project’s intrinsic question is whether and how intergroup emotions can be regulated to alter attitudes and behavior towards peace. I offer an innovative path, using two strategies of emotion regulation. The first is Direct Emotion Regulation, where traditional, effective emotion regulation strategies can be used to change intergroup emotional experiences and subsequently political positions in conflict situations. The second, Indirect Emotion Regulation, serves to implicitly alter concrete cognitive appraisals, thus changing attitudes by changing discrete emotions. This is the first attempt ever to integrate psychological aggregated knowledge on emotion regulation with conflict resolution. I propose 16 studies, conducted in the context of the intractable Israeli-Palestinian conflict. Seven studies will focus on direct emotion regulation, reducing intergroup anger and hatred, while 9 studies will focus on indirect regulation, aspiring to reduce fear and despair. In both paths, correlational and in-lab experimental studies will be used to refine adequate strategies of down regulating destructive emotions, the results of which will be used to develop innovative, theory-driven education and media interventions that will be tested utilizing wide scale experience sampling methodology. This project aspires to bridge the gap between basic and applied science, creating a pioneering, interdisciplinary framework which contributes to existing knowledge on emotion regulation in conflict and implements ways to apply it in real-world circumstances.

1 499 344 €

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

Soon after new antibiotics are introduced, bacterial strains resistant to their action emerge. Recently, non-specific factors that promote the later appearance of specific mechanisms of resistance have been found. Some of these so-called global factors (as opposed to specific resistance mechanisms) emerge as major players in shaping the rate of evolution of resistance. For example, a mutation in the mismatch repair system is a global genetic factor that increases the mutation rate and therefore leads to an increased probability to evolve resistance. In addition to global genetic factors, it is becoming clear that global phenotypic factors play a crucial role in resistance evolution. For example, activation of stress responses can also result in an elevated mutation rate and accelerated evolution of drug resistance. A natural question which arises in this context is how sub-populations of phenotypic variants differ in their evolutionary potential, and how that, in turn, affects the rate at which an entire population adapts to antibiotic stress. I propose a multidisciplinary approach to the systematic and quantitative study of the non-specific factors that affect the mode and tempo of evolution towards antibiotic resistance. Our preliminary results indicate that the presence of dormant bacteria that survive antibiotic treatment affects the rate of resistance evolution in bacterial populations. I will exploit the established expertise of my lab using microfluidic devices for single cell analyses to track the emergence of resistance at the single-cell level, in real-time, and to study the correlation between the phenotype of single bacteria and the probability to evolve resistance. My second approach will take advantage of the recent developments in experimental evolution and high throughput sequencing and combine those with single cells observations for the systematic search of E.coli genes that affect the rate of resistance evolution. We will study replicate populations of E.coli, founded by either laboratory strains or clinical isolates, as they evolve in parallel, under antibiotic stress. Evolved populations will be compared with ancestral populations in order to identify genes and phenotypes that have changed during the evolution of antibiotic resistance. Finally, in silico evolution that simulates the experimental conditions will be developed to analyze the contribution of global factors on resistance evolution. The evolution of antibiotic resistance is not only a fascinating demonstration of the power of evolution but also represents one of the major health threats today. I anticipate that this multidisciplinary study of the global factors that influence the evolution of resistance, from the single cell to the population level, will shed light on the mechanisms used by bacteria to accelerate evolution in general, as well as provide clues as to how to prevent the emergence of antibiotic resistance.

1 458 200 €

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

The general framework is that of game theory, with multiple participants ( players ) that interact repeatedly over time. The players may be people, corporations, nations, computers even genes. While many of the standard concepts of game theory are static by their very nature (for example, strategic equilibria and cooperative solutions), it is of utmost importance theoretically as well as in applications to study dynamic processes, and relate them to appropriate static solutions. This is a fundamental issue. On the one hand, the significance of a solution depends in particular on how easy it is to reach it. On the other hand, natural dynamics, that is, processes that to a certain degree reflect observed behaviors and actual institutions, are important to study and understand in their own right. We propose to work on three main areas. First, adaptive dynamics: the goal is to characterize those classes of dynamics for which convergence to Nash or correlated equilibria can be obtained, and those for which it cannot, and to find and study natural dynamics that are related to actual behavior and yield useful insights. Second, evolutionary dynamics: the goal is to investigate evolutionary and similar dynamics, with a particular emphasis on understanding the role that large populations may play, and on characterizing which equilibria are evolutionarily stable and which are not. Third, bargaining and cooperation: the goal is to develop a general research program that studies natural bargaining procedures that lead to cooperation and are based directly on the strategic form; some particular aims are to establish connections between the bargaining institutions and the resulting cooperative solutions, and to analyze relevant economic models.

1 361 000 €

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

Should sovereign governments be accountable only to their citizens or should they also consider the welfare of foreign stakeholders? Traditional doctrines on state sovereignty and citizenship offer a generally negative answer: Absent a specific, voluntarily accepted, treaty-based commitment, sovereign governments usually have no obligation to weigh foreigners’ interests. This traditional vision conceptualizes sovereigns as Janus-faced: Their public face is for domestic stakeholders to whom they are accountable and to whom they owe negative and positive obligations, and their private face is for all other stakeholders to whom their only obligation is the negative one of not inflicting a set of narrowly defined harms. The aim of this project is to revisit this Janus-faced concept of responsibility and to explore broader alternatives and their ramifications. This study will examine the scope of obligations sovereign governments currently have toward foreign stakeholders and humanity at large and will analyze the normative desirability and political feasibility of potential alternative strategies for enhancing sovereign accountability to non-citizens and promoting a more democratic, sustainable, and egalitarian management of public life and scarce global resources. This project will systematically review the extent to which current law (international law and comparative constitutional law) and institutions already regard sovereigns as public authorities accountable to foreign stakeholders. More specifically, this project will apply the general insights to examine the necessary and possible legal and institutional responses to climatic changes in an era of erratic and extreme weather conditions.

1 405 200 €

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

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

Vaccination is widely used to prevent human diseases by inducing the formation of cellular and antibody-mediated immune responses for induction of long lasting immunological memory. Although most studies focus on immune responses elicited against injected immunizations, the simplest delivery of a vaccine regimen is by oral administration. The cellular and molecular components of the antibody immune response in peripheral lymph nodes in response to immunization are well described, however, much less is known about the dynamics of immune cells in gut associate lymphoid tissues (GALT) and adjust intestinal mucosal tissues. In the proposed research plan I will implicate intravital in vivo imaging for analysis of the cellular component of the antibody immune response in intestinal tissues. My goals are: 1. To track germinal center (GC) T cells for prolong time periods in peripheral lymph nodes and GALT and determine if they enter the memory compartment. For this purpose I will develop a new photoactivation method for permanently labeling immune cells and fate tracing of their daughter cells. 2. To examine T-B interactions and their regulation by intraceullar signaling pathways in GALT and to determine where and when class switch recombination to IgA takes place. For this purpose I will use intravital imaging of fluorescent reporter mice. 3. I will analyze the dynamics of plasma cell migration from Peyer’s patches to the mucosa by implementing state of the art photoactivation and imaging techniques that allow prolonged cell tracking. I will also use photoactivation approaches for sorting plasma cells from specific intestinal layers and perform gene expression analysis. 4. I will develop a new method to study dynamics and fate of B cells specific for commensal microbes in the GC, memory and plasma cell compartments. This research plan will extend our knowledge of the antibody immune response in intestinal tissues towards the future design of improved oral vaccinations.

1 375 000 €

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

This project conducts a theoretical, methodological, and normative paradigm shift in the research and analysis of human trafficking, one of the most pressing moral and political challenges of our times. It moves away from the currently predominant approach to trafficking, which focuses on criminal law, border control, and human rights, towards a labor-based approach that targets the structure of labor markets that are prone to severely exploitative labor practices. This shift represents an essential development both in the research of migratory labor practices and in the process of designing more effective, and more just, anti-trafficking measures, that are context-sensitive as well as cognizant to global legal and economic trends. The project will include four main parts: 1) Theoretical: articulating and justifying the proposed shift on trafficking from individual rights and culpabilities to structural labor market realities. 2) Case-studies: conducting a multidisciplinary study of a series of innovative case studies, in which the labor context emerges as a significant factor in the trafficking nexus – bilateral agreements on migration, national regulations of labor standards and recruiters, unionization, and voluntary corporate codes of conduct. The case studies analysis employs the labor paradigm in elucidating the structural conditions that underlie trafficking, reveal a thus-far mostly unrecognized and under-theorized set of anti-trafficking tools. 3) Clinical Laboratory: collaborating with TAUs Workers' Rights clinic to create a legal laboratory in which the potential and limits of the tools examined in the case studies will be tested. 4) Normative: assessing the success of existing strategies and expanding on them to devise innovative tools for a just, practicable, and effective anti-trafficking policy, that can reach significantly more individuals vulnerable to trafficking, by providing them with legal mechanisms for avoiding and resisting exploitation.

1 492 250 €

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

Marine phytoplankton are the basis of marine food webs and are responsible for nearly 50% of the global annual carbon-based primary production. Since phytoplankton exert such a global-scale influence on climate, we are interested in understanding what controls their cell fate during bloom “boom and bust” dynamics. Despite their importance, the molecular basis for their ecological success is still in its infancy. In recent years, the wealth of genomic information from marine microbes, coupled with molecular resources and analytical tools, provide an unprecedented opportunity to address fundamental questions about their unique evolutionary history and ecological role. Nevertheless, there is a critical need to “decode” the genomic resources and translate them into cellular mechanisms, community structure and, eventually, to their role in ecosystem function. This proposed research aims to provide novel insights into the role of a chemical-based “arms race” that mediates and structures the microbial interactions in the marine environment. We will dissect unexplored signaling pathways employed by phytoplankton during sensing and acclimation to changes in their environment. Our overarching objective is to unravel the role of infochemicals and related gene products in regulating phytoplankton surveillance systems in response to environmental stress conditions. We will focus on the three major biotic interactions of key dominant algal groups in the oceans; intercellular signaling in diatoms, host-virus interactions in coccolithophores and predator-prey interactions. We will provide a suite of cellular probes and metabolic biomarkers that will allow in situ detection of chemical signaling and biotic interactions in the oceans and will highlight their role in shaping microbial food webs. Our vision is to provide novel cellular concepts and molecular tools to the link between the intricate mechanisms of cell signaling and stress response, and large biogeochemical cycles.

1 999 648 €

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

Understanding economic and political integration has long been a central concern for economists. An important missing ingredient in the existing literature is the analysis of endogenously determined social identity. By “social identity” I refer to the fact that individuals often care deeply about the groups to which they belong. By “endogenously determined” I refer to the fact that individuals do not automatically identify with every group they belong to: whether or not an individual identifies with a given group depends on the characteristics of this group as well as on how close to this group the individual perceives herself. Empirical results obtained over the past decade allow us to integrate identity concerns into standard economic models. I propose to develop and test a theory of integration that does just that. Consider two states that may either be independent countries or form a union. The stability and desirability of unification may sometimes depend on the extent to which citizens identify with the union or with their states. But the profile of identities itself depends on the political-economic outcome under unification. The first step in developing the theory is to translate the evidence concerning behavior in groups into a concise statement of what it means to “identify” with a particular group and what factors shape identification decisions. The theory will then study the equilibrium outcomes of a political economy model of integration, where actions and identities are endogenously determined. The second part of the project will empirically examine the relation between social identities, individual characteristics, and European integration. To appropriately measure identification, I propose to employ experimental methods based on revealed preference conducted with a large and diverse sample of European citizens. This will be complemented by historical multi-country survey data on self-reported identity, political attitudes and behavior.

1 050 000 €

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

Contemporary scholarship has often envisioned modernity as a kind of immense cultural earthquake, originating somewhere in western or central Europe, and then gradually propagating throughout the continent. This massive upheaval is said to have shaken the very foundations of every culture it frequented, subsequently eliminating the world which once was, to make way for a new age. This project offers a new understanding of modernization, not as a radical break with tradition, but as the careful importation of new ideas by often timid, almost inadvertent innovators. The project focuses on the rich corpus of translations of non-Jewish texts into Jewish languages, which developed during the early modern period. Largely neglected by modern scholars, these translations played a pivotal role in fashioning Jewish culture from the sixteenth century into modern times. Jewish translators were never merely passive recipients of their non-Jewish sources; they mistranslated both deliberately and accidentally, added and omitted, and harnessed their sources to meet their own unique agendas. Throughout the process of translation then, a new corpus was created, one that was distinctly Jewish in character, but closely corresponded with the surrounding majority culture. JEWTACT offers the first comprehensive study of the entire gamut of these early modern Jewish translations, exposing a hitherto unexplored terrain of surprising intercultural encounters which took place upon the advent of modernity—between East and West, tradition and innovation, Christians and Jews. The project posits translation as the primary and most ubiquitous mechanism of Christian-Jewish cultural transfer in early modern Europe. In so doing, I wish to revolutionize our understanding of the so-called early modern “Jewish book,” revealing its intensely porous, collaborative and innovative nature, and to offer a new paradigm of Jewish modernization and cultural exchange.

1 496 900 €

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

“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 link between inflammation and cancer is now established, yet the underlying molecular mechanisms are unresolved. As tumors progress, they modulate inflammatory cells towards a pro-tumorigenic phenotype. We have shown that inflammatory cells reciprocate by sculpting the parenchymal epithelial cells. I hypothesize that these reciprocal interactions lie at the heart of the link between inflammation and cancer. Hepatocellular carcinoma (HCC), one of the deadliest tumors, is a prototype of inflammation induced cancer. My team will employ a twofold strategy to analyze the changes occuring in inflammatory cells before and after tumors emerge, based on preliminary findings showing that changes in inflammatory cells precede tumorigenesis. First, we will perform comprehensive mapping of the changing inflammatory microenvironment in a mouse model of inflammation induced HCC. We will employ genetic manipulation strategies, coupled to cell isolation techniques to delineate the molecular cues that mediate these changes and then will analyze the functional role of key mediators of these processes in HCC. Microfluidics approaches will give us a highthroughput quantitative view of these heterotypic interactions. The same approaches will be harnessed to identify the interactions that form the liver stem cell niche which dramatically expands in states of chronic inflammation. Second, drawing on our finding that a recurring tumor amplicon drives HCC progression by modulating the microenvironment, we will work towards identifying additional similar amplicons to define additional key effectors of the microenvironment. Of special importance, heterotypic cell interactions that play key roles in both cancer initiation and progression, present ideal therapeutic targets, which are easily accessible and less amenable to mutational selection. Furthermore, the results of our experiments could also have far reaching implications in other inflammatory states and different types of cancer.

1 499 940 €

Start date: 2011-10-01, End date: 2017-09-30

Malaria, caused by Plasmodium falciparum, is a devastating parasitic disease effecting hundreds of millions of people worldwide. The parasite’s transmission cycle between humans and mosquitoes involves a remarkable series of morphological transformations. While it is clear that, for such a complex journey, the parasites must develop means to sense their host and coordinate their actions; these modes of communication remain one of the greatest mysteries in malaria biology. In fact, since an individual parasite is enclosed by three membranes inside its human host, the red blood cell (RBC), they were not thought to possess any communication ability. However, we discovered that these parasites, despite the multiple barriers, are able to communicate and exchange episomal genes by releasing exosome-like vesicles, thereby opening the exciting new field of malaria parasite communication. Our initial data demonstrate that these vesicles serve as a secure tool for the delivery of remarkable components. The overarching goal of this proposal is to take an innovative look at this under-investigated area of parasite sensing and signalling pathways and to decipher the multiple layers of parasite and host signalling networks. Specifically, we will determine the biological roles of Plasmodium exosome cargo components in: parasite-parasite communication - exploring parasite coordination traits in cell-density growth and sexual development (Objective 1); and parasite-host communication - unravelling the mutual communication of the parasite and its hosts, the red blood and immune cells (Objective 2). Simultaneously, we will exploit our experience in cell communication research to investigate the complementary, yet-to-be-explored mode of parasite communication via the secretion of small molecules (Objective 3). Our project will provide a holistic view of parasite communication networking while potentially providing, in the long term, novel targets for malaria therapeutics.

1 500 000 €

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