ERC FUNDED PROJECTS

Under Mendelian inheritance, individuals receive one set of chromosomes from each of their parents, and transmit one set of these chromosomes at random to their offspring. Yet, in thousands of animals Mendel's laws are broken and the transmission of maternal and paternal alleles lose their symmetry. A large body of theory suggests that these asymmetries might arise because of maternal–paternal genetic conflict, but empirical tests are sorely needed to test whether the plausible is actual. This proposal aims to understand why, when and how the transmission of genes from one generation to the next deviates from Mendel’s laws. We ask how different types of sexual conflict -- both directly between parents (interlocus sexual conflict), indirectly between the parent’s genes within their offspring (intragenomic sexual conflict), and between genes expressed in males and females (intralocus sexual conflict) -- can affect the evolution of non-Mendelian reproduction. We focus on species with extreme reproductive asymmetry known as Paternal Genome Elimination (PGE). PGE males systematically transmit only those chromosomes that they inherited from their mother. This unusual reproductive strategy is thought to originate from a clash of interests between the sexes, where mothers have “won” by monopolizing the parentage of their sons. Although PGE is rarely studied, its repeated evolution and experimental tractability make it an ideal test case for understanding the role of sexual conflict in the evolution of genetic systems.

1 494 055 €

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

Emergence of antimicrobial resistance (AMR) is a grand scientific challenge of our time that has killed more than 700,000 people worldwide. Phage therapy, a promising complement to antibiotics, utilizes viruses of bacteria (bacteriophages) or phage-derived inhibitors as natural ways to fight AMR. The main obstacles in the clinical application of phage-based AMR therapy are the limited number of phage isolates and the unknown molecular mechanisms of phage-delivered bactericidal action. Building on the recent advances of my group in high-throughput, culture-independent but host-targeted methodologies, PHARMS aims to deploy a revolutionary approach: to screen for all possible phages of a resistant bacterial isolate, characterize multiple lines of their bactericidal functions, and use this information for the design of a whole battery of phage-based therapies that employ multifaceted modes of action. Using an interdisciplinary research plan, PHARMS will discover phage-specific bactericidal action modes at all possible levels ranging from nucleotide sequence and transcription to translation, in order to elucidate the molecular mechanisms driving phage-mediated inhibition of AMR Acinetobacter baumannii, Helicobacter pylori, & Haemophilus influenzae (WP1). These discoveries, together with novel synthetic biology tools, will enable us to engineer an array of phage vectors that mimic phage-deployed bactericidal modes discovered under WP1, including transport of alien genes to deliver bactericidal effects (WP2). PHARMS will provide molecular confirmation and in vitro & in vivo validation of the functions of phage-encoded bactericidal peptides and enzymes (WP3). By elucidating universal and specific mechanisms of phage-delivered inhibition of AMR pathogens, PHARMS is positioned to provide the rational framework for the design of novel therapeutic strategies aimed at treating common and life-threatening infectious diseases.

1 499 650 €

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

Understanding the evolution of all living organisms is one of the fundamental challenges in biology. The phylogenetic analysis of whole genomes has already proven very useful to decipher not only their history, but also their organization and function. Indeed, the accuracy of these inferences is intimately related to the quality of the models assumed. Despite important advances, models of genome evolution are still in its infancy, and more realistic models are needed to provide more precise and reliable inferences from genome data. In addition, a number of phylogenomic algorithms have been proposed to estimate phylogenies from complete genomes based on different genomic features. Although the application of these methods has already led to critical conclusions regarding the tree of life, the relative performance of these algorithms has not been properly evaluated yet. The first objective of this grant is to develop more realistic models of genome evolution, integrating changes in gene content and changes in gene sequences, and allowing for model variation along different branches of the phylogeny. In order to avoid model overparameterization, a statistical framework for the selection of best-fit models of genome evolution for the data at hand will also be implemented. Genome data simulated under these models will be used to compare the performance of different phylogenomic algorithms. Optimized phylogenomic strategies will then be applied to available genomes in order to decipher unresolved portions of the tree of life. Finally, all the bioinformatic tools developed under this grant will be made freely available to the scientific community.

994 800 €

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

In 2015, nearly all nations agreed on a set of ambitious Sustainable Development Goals (SDGs) to ensure environment protection and human development. Accounting for the coherence of the overall set of goals presents a major scientific challenge as there are many complex relationships and feedbacks between them and across various scales (local to global, near- and long-term). However, in fact very little scientific information exists on how to achieve such a diverse set of goals simultaneously. In the proposed research, I will address the scientific gap by developing a novel set of model-based scenarios that explore the efforts required to achieve a set of key sustainable development targets by 2050 simultaneously (i.e. using a backcasting approach). These targets are based on the SDGs and other international agreements, and cover key sustainability issues such as food production, energy and land use, climate change, water scarcity, and nutrient cycles. The purpose of the analysis is to identify 1) transformation processes needed for achieving these targets (including timing), 2) key synergies and trade-offs among sustainability issues, and 3) the relationships between different geographic scales. In PICASSO, I will use the integrated assessment model IMAGE 3.0 to develop such scenarios and explore the key linkages. For this purpose, important model improvements will be made to better cover the feedbacks and response options relevant for the SDG targets. Additional project activities will cover uncertainty analysis, and questions related to implementation (the role of different actors in these transitions). Stakeholder interaction is vital and will be formalised in a project forum with key stakeholders that will meet on a regular basis. The scenarios may thus be used to implement and evaluate the SDGs, and they will also result in new scientific understanding of integrated response strategies that can be used by other researchers in more detailed analysis.

2 000 000 €

Start date: 2019-06-01, End date: 2024-05-31

Viruses (phages) influence many aspects of microbial processes including the population dynamics, diversity and evolution of their hosts. Yet we know practically nothing about the physiological interactions between hosts and phages during infection even though it is the outcome of these very interactions that affects the above-mentioned processes. Using marine cyanobacteria as a model system I propose to study the physiological interactions between ecologically important microbes and the phages that infect them to gain an understanding of the mechanisms through which they impact microbial ecology processes. Cyanobacteria are an important component of marine phytoplankton and contribute significantly to primary production in vast regions of the world’s oceans. The specific objectives of this proposed study are to: (1) Identify phage genes involved in taking over host metabolic processes; (2) Assess the fitness advantage to the phage provided by bacterial-like genes in phage genomes; (3) Develop a genetic manipulation system for cyanobacterial phages to determine the function of genes in (1) and (2); (4) Discover genes functioning in host defense mechanisms in diverse cyanobacterial-phage systems using whole-genome expression analysis and the generation of phage resistant strains; (5) Determine the impact of genes identified in (4) above on host fitness and phage development during infection. Discovery of the mechanisms employed by phage for taking over host metabolic processes and the defense mechanisms set into motion by the host to overcome phage infection will provide insight into how such interactions influence the diversity and evolution of both cyanobacteria and their phages. Furthermore, this study has high potential for uncovering new bacterial defense mechanisms as well as the discovery of novel viral mechanisms for shutting down bacterial metabolic processes, both of which may also have future practical applications.

1 582 200 €

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

This project will identify the principles governing genome replication in relation to the chromatin landscape and how they impact on plant organ growth. The results will provide the basis to design novel strategies to improve plant growth performance. The large plant genomes, as in all eukaryotes, must be faithfully duplicated every cell cycle, a process regulated at the level of DNA replication origins (ORIs). Our understanding of how ORIs are determined is still very limited. Most of our knowledge comes from cultured cells, precluding the identification of regulatory layers operating at the organism level. Importantly, genome replication can offer unexplored possibilities to modulate plant architecture and growth and, consequently, plant performance. Results generated so far unable us to address a fundamental question: what are the regulatory mechanisms of DNA and genome replication and how they can be exploited to design improved plant growth strategies. This innovative perspective will reveal how genome replication is regulated by DNA sequence context, replication factors and chromatin landscape. Integration of molecular, cellular, genomic and genetic approaches in a whole organism will serve to evaluate the phenotypic effects of modulating genome replication on organ growth. We will also learn how DNA replication control is exerted during endoreplication and in coordination with transcriptional programs, both crucial for plant organogenesis, growth and response to environmental stresses. This program goes beyond incremental research, is timely, innovative, ambitious but realistic, and high risk/high gain, combining different approaches to address a fundamental process. Given the conservation of proteins and pathways, and the availability of well-annotated genomic information for many plant species, PLANTGROWTH will pave the way to translate the technological and conceptual know-how derived from this program to crop species to improve yield.

2 497 800 €

Start date: 2019-06-01, End date: 2024-05-31

The burdens of dealing with administrative rules and red tape in government are a fact of life around the world, ranging from small hassles to heavy burdens in the form of stigmatizing processes of proving eligibility and facing potential sanctions. In light of the immense importance of such burdens for millions of people and for the effectiveness of benefit programs, we know surprisingly little about the conditions that give rise to experiences of burden. POAB combines and extends extant theory and uses a unique combination of experimental methods and data to explain how, why, and for whom administrative rules are experienced as burdensome. POAB studies comprehensive rules regarding unemployment and social benefits and will provide novel register, physiological, and survey measures of welfare benefit recipients’ experiences of burden. I develop and test three theories to explain differences in experiences of burden: 1) How resource scarcity causes cognitive load and hence reduces the ability to cope with rules; 2) How self-efficacy increases the ability to cope with rules; and 3) How perceptions of being undeserving cause stigma and stress. POAB analyses the causal impact of rules on burden. To this end, I use a unique combination of complementary experimental methods in political science: 1) Cross-national lab experiments with physiological measurement and manipulations of rules, scarcity, efficacy and deservingness perceptions; 2) Cross-national survey experiments to assess different aspects of rules in different contexts; 3) Quasi- and field experiments to assess the impact of rules on register measures of burdens in a real-world context. POAB offers a fundamentally new interdisciplinary approach by bridging the gap between research on administrative burdens and psychological perspectives. The project’s output will provide profound knowledge of citizens’ experiences of burden and the inequalities in such experiences among recipients of major welfare benefits.

1 499 611 €

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

From Victorian women cyclists, who suffered social stigma for daring to replace their skirts with bloomers a century ago, to the recent French burkini ban, where women were forcibly removed from beaches, specifically clothed bodies have long been sites of debate about gender, race, class and religion in public space. Clothing is directly connected to social life and the political world and as such is central to ideas around the politics of identity, participation and belonging. Yet, it is under explored in relation to citizenship studies. This five-year project undertakes for the first time a transnational sociological investigation of 200 years of clothing inventions. It focuses on clothing patents in Espacenet, the European Patent Office’s free online database. Inventors are the focus as they operate on the cutting edge of social and political change; building on the past to make claims on the present and imagine different futures. Central to this research is the idea that clothing inventors can be explored as citizen-makers and that clothing patents are rich untapped sources of data that render visible alternative citizenship possibilities, which may provoke new questions about things we take for granted. The research will be located in a Patent Lab using an inventive mixed-methods approach including quantitative and in-depth visual and document analysis, interviews with inventors and garment reconstruction.

1 802 154 €

Start date: 2019-03-01, End date: 2024-02-29

The model predatory bacterium Bdellovibrio bacteriovorus feeds upon other Gram-negative bacteria, including pathogenic strains. Upon entry inside the periplasmic space of the prey envelope, B. bacteriovorus initiates an exquisite developmental program in which it digests the host resources while ensuring the osmotic stability of its niche. In the periplasm, the predator cell grows as a polyploid filament, before releasing a variable, odd or even number of daughter cells upon a non-binary division event. The progeny is then liberated to hunt for new prey. B. bacteriovorus is now attracting a revived attention as several in vivo models of infection established its promising “living antibiotic” potential. Despite this remarkable lifestyle, the fields of bacterial cell biology and antibiotics research still lack a comprehensive understanding of how this micro-predator thrives inside the envelope of other bacteria. Indeed, the molecular factors behind the non-canonical cell biology of B. bacteriovorus are still largely mysterious. My goal is to tackle this question by unraveling the novel mechanisms that control key processes of the fascinating cell cycle of this bacterium, using a unique combination of quantitative live imaging of predation at the single-cell level, bacterial genetics and molecular biology. Specifically, I aim to (i) uncover how the genetic information is organized, copied and partitioned in a polyploid cell before non-binary division, (i) shed light on factors that polarize the predator cell, and (iii) discover prey envelope features that influence the predation cycle. Because the biology of B. bacteriovorus stands beyond textbook standards, our results will provide mechanistic insight into important biological questions that remained unexplored using “classical” model species. If successful, this project will advance bacterial cell biology, while offering an innovative contribution to the fight against antibiotics-resistant pathogens.

1 499 688 €

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

This project analyzes the distribution, origin, determinants and consequences of human preferences. Preferences are key building blocks of any economic model and fundamentally determine human behavior both at an individual and a country wide level. Four particularly important types of preferences, which will be studied in this research project, are risk preferences, time preferences, social preferences and preferences for work and leisure. Despite their fundamental importance, empirical knowledge regarding the nature of preferences is still very limited. Crucial open questions concern: the pervasiveness of different degrees of risk aversion, impatience, social preferences and preferences for work and leisure in the population; the extent to which different preferences vary systematically with personal characteristics, such as gender, age, and educational background; the correlation between preferences within person, e.g., whether individuals who are risk averse also tend to be impatient; the relation between economic preferences and other non-cognitive skills, such as personality (e.g., Big Five) and cognitive skills measured in terms of IQ; the origin of preferences, e.g., the extent to which preferences are passed on from one generation to the next; the possibility that preferences and attitudes vary systematically with the social and institutional environment; and the degree to which individual preference endowments differ across populations and countries. Answering theses questions is of great importance, both from a general research perspective as well as from a policy oriented point of view. This project is highly innovative as it combines experimental and survey techniques and because it bridges insights from many disciplines.

1 340 000 €

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

The research project will use theoretical models and empirical techniques to explore the causes, consequences, and prevention mechanisms of conflicts. The aim is to determine the basic elements that make countries more prone to social conflicts and then identify a set of feasible policies to prevent future episodes of violence. The project considers the causes and the propagation mechanisms of social conflicts of different intensity. The main objective of the project is to the study the institutional designs that may prevent, or mitigate, such social conflicts. Therefore, the analysis of economic institutions (such as property rights, etc.), political institutions and structure (democracy, decentralization, political systems, etc.), and the type of political leaders, that can help to prevent, conflict in potentially conflictive societies. From a methodological perspective, the project proposes to overcome some statistical pitfalls present in most of the previous literature on the determinants of civil wars and conflicts. The use of simple linear regressions, or a probit/logit specification, imposes very strong identification conditions that are likely to be violated. The current consensus, which emerges from those analyses, is that poverty is the single, most important determinant of civil wars. This result could be an artifact of simultaneity problems: the incidence of civil wars and poverty may be driven by the same determinants, some of which are probably missing. We propose to check the robustness of this consensus idea, and the importance of the institutional design, using other econometric procedures (instrumental variables and matching methods) which are subject to weaker identification conditions than the traditional regressions. Finally, we plan to investigate methods to deal with the missing data problem that plague the study of the determinants of civil wars.

1 330 000 €

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

Sensory perception has recently emerged as a master regulator of integrative physiology and behavior, including feeding, by controlling fundamental and pleiotropic regulatory processes of energy and glucose homeostasis. Further, sensory perception is altered in obesity and type 2 diabetes, and childhood obesity correlates with early sensory deficit. Along this line, the discovery of the developmental origins of health and diseases revealed that metabolic diseases have recognized roots in the very early stages of life and can be predisposed to by changes in the perinatal hormonal and nutritional environments, such as occur in cases of maternal obesity and unhealthy diet. In this context, an accumulating body of evidence suggests that maternal health and nutrition could negatively impinge on the development of sensory perception, and subsequently, on the lifelong regulation of sensory-dependent control of metabolic, physiological, and behavioral regulatory processes. This innovative research program consists of four autonomous but complementary projects aimed at (1) deciphering the exact central regulatory processes mediating sensory control of feeding behavior and glucose homeostasis, (2) uncovering the influence of maternal health and nutrition on lifelong sensory regulation of metabolism, and (3) & (4) investigating two independent, yet synergistic, mechanisms that could mediate developmental programming of sensory metabolic regulation. This research program will employ a technology framework of physiological, behavioral, and developmental analyses in mice in concert with state-of-the-art systems neuroscience approaches, including optogenetics, chemogenetics, and in vivo calcium imaging. Collectively, the overarching goals of this research program are to provide new insights into the precise regulatory processes of sensory metabolic regulation and to shed light on critical basic mechanisms underlying the developmental programming of metabolic diseases.

1 500 000 €

Start date: 2019-06-01, End date: 2024-05-31

The innate antiviral defense system is of central importance to protect from viral pathogens. Its ability to mitigate a detrimental outcome of an infectious event relies on interactions that happen between viral and host-derived proteins as well as on signalling cascades that regulate the cellular response. However, despite the importance of these interactions, the involved processes and proteins are not yet fully understood. We established state of the art mass spectrometry techniques and statistical modelling to characterise protein-protein interactions that are affected by viruses. We identified a class of proteins we name “viral affected proteins changing their interaction” (iVAPs). In addition, we established protein turnover rates of >6900 proteins in virus infected cells and identified a group of “viral affected proteins changing turnover rates” (tVAPs). tVAPs are regulated on basis of protein stabilisation, degradation or translation. Preliminary experiments show critical importance of iVAPs and tVAPs in antiviral immunity, suggesting functional similarities to Interferon stimulated genes (ISGs). Alike ISGs, VAPs therefore represent a critical component of the immune system. ProDAP will establish the function of iVAPs and tVAPs in the antiviral immune response. Systematic screens employing depletion and overexpression experiments, integration of these data in functional networks and mechanistic follow up studies will be performed. Already identified and new candidate proteins will be tested mechanistically for their immune-regulatory capacity and their influence on virus infections in vitro and in vivo. ProDAP will allow insights in yet unstudied modulators of host-pathogen interplay and will influence our current understanding of immune regulation in general. It is well established that ISGs are of central importance to defend virus infections and we hypothesize that VAPs may fulfil a similarly important protective function that has yet not been elucid

2 169 555 €

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

People’s lives, both as individuals and at the collective level, are guided by projections about the future. This project aims to understand the complex processes through which projections about political issues, such as the outcomes and implications of elections, referenda, crises or wars, are formulated and negotiated within and through the media. It develops a new interdisciplinary approach and research tools for studying how projections evolve over time and through the contribution of various social actors (such as politicians, experts and journalists), and how they are received and acted upon by the public. The focus is on at least three retrospective case studies (projections about the Brexit referendum; the civil war in Syria; and Donald Trump's presidential bid) as well as three real-time case studies (to be selected based on geopolitical developments), characterised by high-visibility and involving projections with far-reaching implications. PROFECI integrates cutting-edge qualitative, quantitative and automated approaches to capture the interactive process underlying the construction and evolution of public projections, and their reciprocal relationship with people’s expectations and behaviour. It begins with an in-depth investigation of the construction, transformation and reception of projections made by key actors, using textual analysis of the source projections and their journalistic coverage, reconstruction interviews with experts and journalists, and focus groups with public members. The results of this stage inform the development of tools for a large-scale diachronic automated text analysis and panel surveys, which will be applied to the real-time and the retrospective case studies. By elucidating the life cycle of projections in a mediated environment, PROFECI opens up new avenues for understanding and researching adaptive social processes, such as self-fulfilling and self-defeating prophecies, and the role of the media in shaping the future.

1 499 732 €

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

My recent findings revealed translation of numerous previously unidentified (small) open reading frames and expression of alternative N-terminal proteoforms when studying bacterial translation. This proposal aims at unraveling the repertoire of bacterial pathogen proteoforms employed to establish a successful infection in a mammalian host cell. While deep sequencing has enabled the study of gene expression at the transcript level in both pathogen and host simultaneously, the depth of sequencing has so far proven to be unsatisfactory. Moreover, the study of bacterial proteome changes upon infection remains highly unexplored because of the higher proteome complexity of the host cell compared to the pathogen. These challenges clearly stresses the need for novel strategies based on complementary proteogenomics approaches enabling translation control studies in bacterial pathogens in a host context . I here propose the development and application of a complementary cutting-edge proteogenomic toolset which will enable for the first time targeted systematic genome- and proteome-wide surveys of bacterial transcriptional and translational activity during actual host cell infection. This ambitious endeavor will lead to: I) Establishment of dual Ribo-seq that allows the selective isolation of host or bacterial ribosomes, enabling to study the bacterial translatome in a host cell context. II) Development of tailored proteomics strategies permitting the selective isolation of (nascent) bacterial protein N-termini and enrichment of bacterial small ORF-encoded polypeptides (SEPs). Further, proteome-wide subcellular localization and protein stability studies will provide a dynamic view on bacterial protein expression. II) Bacterial proteoform interaction maps by the development of an innovative proxeome strategy. The identification of new pathogen virulence factors will contribute to the development of therapeutics and diagnostics for multiple models of infectious diseases.

1 498 625 €

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

Despite progress in cancer drug development, the majority of patients who present with advanced, metastatic, solid tumours have incurable disease due to underlying cancer genomic diversity that provides a substrate for evolution and selection of drug resistance. The aim of this proposal is to describe, synthesise and model the micro- and macroevolutionary patterns of genomic instability underpinning the evolutionary dynamics of tumour life histories, to improve patient stratification, treatment and survival outcomes. Longitudinal clinical studies such as TRACERx are highlighting the complex processes that generate this intra-tumour heterogeneity (ITH). Genome Instability (GIN) describes aberrant changes within the genome, encompassing genome doubling (GD), numerical or structural chromosomal instability (CIN), and elevated DNA sequence mutational diversity. TRACERx has revealed that elevated DNA copy-number ITH rather than DNA sequence diversity is associated with increased risk of recurrence or death in non-small cell lung cancer (NSCLC). Why macroevolutionary CIN rather than somatic mutational diversity is associated with poor outcome remains unclear. Current animal models of NSCLC do not sufficiently model the multiple distinct patterns of GIN operating in patients. We aim to develop mouse lung cancer models that recapitulate the patterns of GIN observed in NSCLC patients. Using tumour barcode sequencing, a sensitive method of quantifying cellular fitness and individual tumour growth, we will investigate the effects of targeted-, chemo- and immuno-therapy on the newly generated GIN models. We will decipher if distinct patterns of GIN increase metastatic potential and treatment failure, and test if high mutational burden or high CIN increases the frequency of GD in cancer. Finally, we aim to investigate the effects of GIN upon immune surveillance, immune evasion, immunotherapy response, and the interactions between tumours and the tumour microenvironment.

2 500 000 €

Start date: 2019-06-01, End date: 2024-05-31

"One of the major goals of post-genomic biological research is to understand the molecular basis and physiological role of covalent protein modifications. Post-transcriptional modifications can regulate protein interactions and/or stability and thus trigger particular downstream responses. A major challenge is to understand how modifications of histone proteins are translated into changes in gene expression and chromatin structure and how they regulate genome function. However, the significance of studying protein modifications extends beyond the field of chromatin research, because changes in the modification pattern are likely to affect many -if not all- biological processes. This proposal is designed to study and functionally characterise modifications of histones. The goals of this proposal are: A) Determining the role of linker H1 modifications and variants in epigenetic regulation of gene expression. This will enable us to expand the ""histone"" code to the next higher level of chromatin organisation. B) To identify yet uncharacterised sites or new types of histone modifications. This will be the basis for determining the biological function of these modifications. Altogether this will lead us to decipher the role of covalent protein modifications in regulation of gene expression and how they are linked into biological networks . These projects will significantly expand the scope of my ongoing research and will only be possible with additional funding, which will allow me to establish cutting edge technology, additional in vivo model systems and new interdisciplinary collaborations."

1 239 400 €

Start date: 2008-09-01, End date: 2014-08-31

This project aims at transcending boundaries between « high » and « popular » cultures, here established playwrights and anonymous writers, by investigating their productions for a same medium: puppet and marionette theatre. Focusing on key-periods of drama history (1600-2000) it explores how puppeteers and authors both contribute to the raise of a specific dramaturgy. Introducing these repertoires into the history of Western European drama opens a double ground-breaking perspective: on one side, it exceeds the limits of local inquiries and reveals cultural transfers through social groups and nations; on the other, it leads to reexamine theatre historiography by considering the cohesion of “theatrical systems” (Marotti) and giving visibility to a long despised and scatered corpus. The main objectives are 1) to gather a corpus of representative plays which document the development of puppetry in Western Europe (Austria, Belgium, England, France, Germany, Italy, Nederlands, Portugal, Spain); 2) to identify the specific features of puppet and marionette plays and their variations through time, cultural areas, conditions of production and targeted audiences; 3) to re-evaluate the contribution of these repertoires to the construction of European cultural identity. The principal investigator brings to this project, besides a long experience of internationally recognized research, an excellent knowledge of artistic and cultural networks which guarantees the access to primary sources as well as the mobilisation of experts and partner institutions. Using digital humanities tools and methods, the project will produce a platform making available the selected corpus through a data base and searchable thesaurus, and offering innovative resources to the research community, pedagogues, practitioners and public at large. The research will lead to a better integration of puppetry into theatre history, an increased knowledge of its heritage, and a growing institutional recognition.

2 288 832 €

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

In the context of unprecedented anthropogenic forcing in the living world, the speed and mechanisms of evolution remain the key to many questions ranging from pathogens adaptation to the dynamics of biodiversity. To what extent can evolutionary theory make predictions? What would be the time horizon of such predictions? These are the two questions I would like to address with this project. Experimental evolution with microbes is now a standard in studying evolution. It represents both unprecedented experimental progress in this field but also a real challenge to the theory. This project is organized into three parts. In the first, the aim is to develop mutation models to account for the diversity of possible mutation effects in evolutionary models. A major challenge is to be able to frame these models in terms of measurable quantities so that they can be tested and calibrated with appropriate data. The second aim is to build synthetic quantitative evolution models. Clearly, this development does not start from scratch. However, the development of current theory has to be made in two particular directions. First, it is necessary to incorporate the distribution of mutation fitness effects in evolutionary models. Second it is needed to incorporate explicit demography. In the third part, the aim is to develop empirical systems to confront the theory. One of the central issues is to develop biological models in which evolution can be measured on significant time scales. Microorganisms are ideal for this purpose and I will set up experiments with Escherichia coli to study niche evolution. However, it is also crucial to measure evolution in natura, so that I will also develop an alternative model system (Artemia spp.) with which field individuals several hundred generations apart can be compared and crossed. This unique model system will be particularly useful to test quantitative evolution models.

884 400 €

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

This project examines the formation and differentiation of princely elites in pre-modern European rank societies. The project concentrates on the late Middle Ages (1200–1500), a key period in these processes, with geographic focus on the Empire and England. In both polities new princely elites emerged during this period. Yet, they did so in the context of the establishment of two different monarchical principles, the elective kingship in the Empire and the hereditary kingship in England. In the Empire, the electoral princes became a distinctive group and constituted themselves as the pillars of the imperium. In England, the title of duke appears to have been introduced to distinguish members of the royal family from other magnates. In examining these complex social and political processes in both polities the project contributes to establish a typology of different ways of constructing societies in pre-modern Europe using an interdisciplinary, comparative approach. The project combines history, architectural and art history, archaeology and semiotics to analyse princely actions, princely architecture and heraldry. In so doing we will endeavour to determine the strategies developed and deployed by princes in late medieval Europe to represent and improve their rank and thus their significance. The comparison sheds light on several key issues such as whether the emperorship, unique in Europe, enabled the development of a king-like position for (electoral) princes, and how in different political contexts the position of the magnates in relation to each other and the king was communicated and perpetuated. This project breaks new ground on several frontiers. Interconnecting different disciplines, it crosses existing subject boundaries and thus opens up new ways of fruitful cooperation. By comparing the Empire with England the project also transgresses the traditional boundaries of national history, thus helping to establish a European perspective in medieval studies.

900 000 €

Start date: 2008-10-01, End date: 2014-09-30

REAL opens up new perspectives in moral and political philosophy by closing the rift between analytical theories of rights and egalitarian theories of distributive justice. There is a perception in both the academic and public discourse that pursuing egalitarian economic policies is incompatible with a commitment to rights. Socialist thinkers have traditionally been sceptical of rights, and contemporary egalitarian theories are often silent about them. At the same time, theories that take rights seriously either neglect the distributive dimension or suggest that egalitarian redistribution may infringe on individual rights. Egalitarianism and rights thus appear to be inhospitable to each other. This project seeks first, to understand what explains this divide and second, to demonstrate that it can be bridged. REAL is motivated by the thought that a theory of justice, including economic justice, would be more action-guiding if it could translate its recommendations into moral and subsequently legal rights. It thus aims to show that egalitarianism is not only compatible with a commitment to rights but that they are mutually supportive. The project has three main objectives: - to refute the idea that the concept of rights rules out egalitarian commitments - to uncover the reasons why egalitarianism is inhospitable to rights and show that they are inconclusive - to propose a rights-friendly egalitarian theory of justice The project will critically examine theories of rights and egalitarian theories of justice and adopts an analytical approach that blends arguments from political and legal philosophy, normative ethics and axiology in order to provide a novel and solid framework that integrates the two and advances current debates in these areas.

1 319 355 €

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

Obesity and eating disorders are critical problems in society. Many patients with these brain diseases cope with stress by ravenous food intake (binge eating), which engenders new stress and maintains the pathology. Evidence-based treatments for this are urgently needed, but their implementation is hindered by a knowledge gap on: (i) which stress-driven neural disruptions cause binge eating, and (ii) whether these neural circuit changes can be normalized for therapeutic gain. Studies in humans and rodents link binge eating to dysfunction of the prefrontal cortex (PFC), a brain region orchestrating the stress response. However, it is unknown how effects of stress on PFC output cause binge eating. The PFC prominently innervates the lateral hypothalamus (LHA), a region with a crucial role in managing food intake, yet little is known about the function of PFC regulation of the LHA. I predict that stress-induced binge eating requires a functional reorganization of prefrontal cortical control over lateral hypothalamus feeding circuits, and that this control can be restored to limit binge eating. I propose a cutting-edge threefold strategy to address these hypotheses in mouse models: 1. I will unravel the make-up of PFC-LHA circuitry, combining electrophysiology, optogenetics and neural tracing. I will assess how stress functionally alters this complex network. 2. I will determine the concurrent activity at multiple sites within PFC-LHA circuitry as mice engage in stress-driven binge eating, using fiber photometric calcium recordings. 3. I will assess if normalizing stress-altered PFC-LHA synapses rebalances this circuitry in vivo and limits binge eating. For this I will combine optogenetic plasticity protocols, with fiber photometric measurements in freely moving mice. Overall, this challenging project aims to unravel the unclear neurobiology of stress-induced binge eating. If successful, this would provide a key advance in understanding binge eating pathologies.

1 499 966 €

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

This project will help to meet the vital need for empirical research into the theory and practice of Payments for Environmental Services (PES). PES approaches to conservation have become rapidly more popular in the last few years, driven by compelling evidence of their effectiveness compared with indirect approaches to financing conservation. This research will exploit a current opportunity to build robust research protocols into the initial design of a PES scheme, thus allowing credible research into its outcomes. This will be undertaken through work with selected communities around the Nyungwe National Park in Rwanda. Communities will be offered cash transfers, contingent on their performance in relation to a set of conservation indicators. One of the great advantages of this project location is the availability of high quality ranger monitoring that, for example, provides regular geo-referenced data on the location of snares, tree-felling and other illicit activities. The outcomes of this experiment will be investigated through interdisciplinary research based on four main types of data. Firstly, data on forest user behaviour, based on the ranger data and additional transect studies; secondly, livelihood surveys that build an understanding of relationships between communities and park resources; thirdly, qualitative data, based on interviews and focus groups, to build an understanding of the social dynamics arising from introduction of the PES scheme; fourthly, public goods games to elicit data on attitudes towards the Park. The research findings will be of use to a wide range of African and international agencies with an interest in better understanding ways of reconciling biodiversity conservation and poverty alleviation. The results will provide a timely input to our understanding of the theory and practice of PES schemes.

1 027 633 €

Start date: 2008-07-01, End date: 2012-09-30

Eukaryotic gene expression is a highly regulated, fundamental cellular process encompassing distinct steps such as transcription, mRNA processing and nuclear export, translation and degradation of the mRNA. In this project a novel level in the regulation of gene expression will be analyzed. We propose that transcription and the correct processing as well as packaging of the newly synthesized mRNA into an mRNP control the translation of this mRNA in the cytoplasm thus coupling intranuclear events in mRNA biogenesis to translation. Recently, we showed that the transcription elongation factor Ctk1 functions as a positive factor in translation elongation by phosphorylating the ribosomal protein Rps2. According to our model, Ctk1 enhances the translation fidelity of mRNAs that have been correctly processed and assembled into mRNPs in the nucleus. In the project proposed here we will analyze how the function of Ctk1 couples transcription to translation and how Ctk1 functions in translation initiation, in support of which we have already obtained evidence. Importantly, we will identify additional players in coupling intranuclear mRNA biogenesis events to translation and unravel their molecular function. In addition, we will determine phosphorylated residues on ribosomal proteins and translation factors, identify their kinases and phosphatases, and analyze the biological significance of these phosphorylation events in translation. Moreover, the conservation in higher eukaryotes of the biological principles obtained with our model organism S. cerevisiae will be assessed. All these experiments are performed under the aspect that the cell uses phosphorylation of ribosomal proteins and translation factors to control the efficient and correct translation of a correctly processed mRNP providing a novel level of gene expression control in eukaryotes.

899 713 €

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