ERC FUNDED PROJECTS

Rates of domestic violence and the relative risk of premature death for women are higher in sub-Saharan Africa than in any other region. Yet we know remarkably little about the economic forces, incentives and constraints that drive discrimination against women in this region, making it hard to identify policy levers to address the problem. This project will help fill this gap. I will investigate gender discrimination from two complementary perspectives. First, through the lens of economic history, I will investigate the forces driving trends in women’s relative well-being since slavery. To quantify the evolution of well-being of sub-Saharan women relative to men, I will use three types of historical data: anthropometric indicators (relative height), vital statistics (to compute numbers of missing women), and outcomes of formal and informal family law disputes. I will then investigate how major economic developments and changes in family laws differentially affected women’s welfare across ethnic groups with different norms on women’s roles and rights. Second, using intra-household economic models, I will provide new insights into domestic violence and gender bias in access to crucial resources in present-day Africa. I will develop a new household model that incorporates gender identity and endogenous outside options to explore the relationship between women’s empowerment and the use of violence. Using the notion of strategic delegation, I will propose a new rationale for the separation of budgets often observed in African households and generate predictions of how improvements in women’s outside options affect welfare. Finally, with first hand data, I will investigate intra-household differences in nutrition and work effort in times of food shortage from the points of view of efficiency and equity. I will use activity trackers as an innovative means of collecting high quality data on work effort and thus overcome data limitations restricting the existing literature

1 499 313 €

Start date: 2018-08-01, End date: 2023-07-31

Present-day financial markets are turning algorithmic, as market orders are increasingly being executed by fully automated computer algorithms, without any direct human intervention. Although algorithmic finance seems to fundamentally reshape the central dynamics in financial markets, and even though it prompts core sociological questions, it has not yet received any systematic attention. In a pioneering contribution to economic sociology and social studies of finance, ALGOFINANCE aims to understand how and with what consequences the turn to algorithms is changing financial markets. The overall concept and central contributions of ALGOFINANCE are the following: (1) on an intra-firm level, the project examines how the shift to algorithmic finance reshapes the ways in which trading firms operate, and does so by systematically and empirically investigating the reconfiguration of organizational structures and employee subjectivity; (2) on an inter-algorithmic level, it offers a ground-breaking methodology (agent-based modelling informed by qualitative data) to grasp how trading algorithms interact with one another in a fully digital space; and (3) on the level of market sociality, it proposes a novel theorization of how intra-firm and inter-algorithmic dynamics can be conceived of as introducing a particular form of sociality that is characteristic to algorithmic finance: a form of sociality-as-association heuristically analyzed as imitation. None of these three levels have received systematic attention in the state-of-the-art literature. Addressing them will significantly advance the understanding of present-day algorithmic finance in economic sociology. By contributing novel empirical, methodological, and theoretical understandings of the functioning and consequences of algorithms, ALGOFINANCE will pave the way for other research into digital sociology and the broader algorithmization of society.

1 590 036 €

Start date: 2017-05-01, End date: 2021-04-30

In this project, innovative techniques to reconstruct ancient economies are developed and new insights in the trade and processing of mineral raw materials are gained based on interdisciplinary archaeological and archaeometrical research. An innovative methodology for and a practical provenance database of the primary origin of natron glass from the Hellenistic-Roman world will be established. The project investigates both production and consumer sites of glass raw materials using both typo-chronological and archaeometrical (isotope geochemical) study of finished glass artefacts at consumer sites as well as mineralogical and chemical characterisation of raw glass and mineral resources at primary production sites. Suitable sand resources in the locations described by ancient authors will be identified through geological prospecting on the basis of literature review and field work. Sand and flux (natron) deposits will be mineralogically and geochemically characterised and compared to the results of the archaeological and geochemical investigations of the glass. Through integrated typo-chronological and archaeometrical analysis, the possible occurrence of primary production centres of raw glass outside the known locations in Syro-Palestine and Egypt, particularly in North-Africa, Italy, Spain and Gaul will be critically studied. In this way, historical, archaeological and archaeometrical data are combined, developing new interdisciplinary techniques for innovative archaeological interpretation of glass trade in the Hellenistic-Roman world.

954 960 €

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

The intention of Beasts to Craft (B2C) is to document the biological and craft records in parchment in order to reveal the entangled histories of animal improvement and parchment production in Europe from 500-1900 AD. B2C will lay the foundations for a new approach to the the study of parchment manuscripts —biocodicology— which draws evidence from the overlooked first stages in production, the raising of livestock and the preparation of the skins. 1. Parchment is an extraordinary but overlooked high resolution zooarchaeological record and a molecular archive. Livestock genetics is revealing breed diversity and markers of character traits such as fleece quality. B2C will exploit this new-found knowledge, using progressively older dated archival (sheep) parchments to study the history of improvement 1300 - 1900. Visual examination of the skins will search for direct evidence of disease and fleece quality. 2. Craft skills can be read from parchment and, when combined with chemical data and comparison with modern analogues, will produce the first European wide record of the craft from 500-1900. The size and scope of this the parchment archive means it is one of the largest and most highly resolved records of a specialist medieval craft. We will explore how these skills develop and when and where regional patterns appear and decline. These two remarkable records requires a large interdisciplinary team. However biocodicology draws from and informs upon a wide and diverse spectrum of existing scholarship in conservation, the arts and sciences. A third strand of the project will (i) furnish manuscript scholars with some of the information available to the scribe at time of production (ii) inform and shape attitudes to parchment conservation (iii) provide high resolution biological data on animal management, movement and health and (iv) explore methods to link datasets and promote data reuse.

2 499 462 €

Start date: 2018-12-01, End date: 2023-11-30

The “Bantu Expansion”, a research theme within the precolonial history of Central Africa, unites scholars of different disciplines. Much research is focused on the initial expansions of Bantu subgroups, which are explained as farmers ever looking for new lands and therefore avoiding the rainforest, also in the recent research on the “Savannah Corridor”. We want to study a crossroads of different Bantu expansions in the very heart of the Central-African rainforest, namely the eastern part of the Congo Basin (the Congo River and its tributaries up- and downstream of Kisangani until Bumba and Kindu). The region hosts multiple language groups from Bantu and other origin, complex ethnic identities and people practicing complementary subsistence strategies. Considering that farming is complicated in a rainforest environment, we will investigate the role of rivers in the settlement of these speech communities into the area, both as ways into the forest and as abundant source of animal protein (fish). The project is multidisciplinary and will apply an integrated linguistic, anthropological and archaeological approach to study both present and past riverside communities in the Congo Basin. Historical comparative linguistics will offer insights into the historical relations between speech communities through language classification and the study of language contact, and will study specialized vocabulary to trace the history of river-related techniques, tools and knowledge. Anthropological research involves extensive fieldwork concerning ethnoecology, trade and/or exchange networks, sociocultural aspects of life at the riverside, and ethnohistory. Archaeologists will conduct surveys in the region of focus to provide a chrono-cultural framework.

1 427 821 €

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

"Bicuspid aortic valve, a heart valve with only two leaflets instead of three, is the most common congenital heart defect with an estimated prevalence of about 1-2%. The heart defect often remains asymptomatic but in at least 10% of the bicuspid aortic valve patients, an ascending aortic aneurysm develops as well. If not detected in a timely fashion, this can lead to an aortic aneurysm dissection with a high mortality. In view of the prevalent nature of this heart defect, this implies an important health care problem. Historically, it was always hypothesized that abnormal blood flow across the bicuspid aortic valve led to aneurysm formation. However in recent years, the importance of a genetic contribution has been suggested based on the high heritability and it is currently believed that the same genetic factors predispose to the developmental valve defect and the aortic aneurysm formation. The inheritance pattern is most consistent with an autosomal dominant disorder with variable penetrance and expressivity. Until now, the latter have significantly hampered the causal gene identification but the era of next generation sequencing is now offering unprecedented opportunities for a major breakthrough in this area. Through detailed signalling pathway analysis, miRNA profiling and next generation sequencing, this project will contribute significantly to resolving the genetic causes of bicuspid related aortopathy, provide critical knowledge on the pathogenesis of aortic aneurysmal disease and deliver a mouse model for future therapeutical trials."

1 497 895 €

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

Constructing Age for Young Readers (CAFYR) CAFYR starts from the observations that Europe has recently witnessed a few pertinent crises in intergenerational tension, that age norms and ageism frequently go unchecked and that they are part of children’s socialization. It aims at developing pioneering research for understanding how age is constructed in cultural products. CAFYR focuses on fiction for young readers as a discourse that often naturalizes age norms as part of an engaging story and that is endorsed in educational contexts for contributing to children’s literacy, social and cultural development. The effect of three factors on the construction of age in children’s books is studied: the age of the author, the age of the intended reader, and the age of the real reader. CAFYR aims to lay bare whether and how the age and aging process of children’s authors affect their construction of the life stages in their works. It will show how various crosswriters shape the stages in life differently for young and adult readers. It considers the age of young readers as varied in its own right, and investigates how age is constructed differently for children of different ages, from preschoolers to adolescents. Finally, it brings together readers of various stages in the life course in a reception study that will help understand how real readers construct age, during the reading process and in dialogue with each other. CAFYR also aims to break new theoretical and methodological ground. It offers an interdisciplinary approach that enriches children’s literature research with concepts and theories from age studies. It combines close reading strategies with distant reading and tools developed for digital text analysis. It provides a platform to people of different stages in life, contributing to their awareness about age, and facilitating and investigating dialogues about age, with the aim of ultimately fostering them more.

1 400 885 €

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

The research project has two broad objectives and provides novel results in the literature of structural change or change-point tests. The first objective is to provide two new methods for restoring the non-monotone power problem of a large family of structural breaks tests that have been widely used in econometrics and statistics, as well as to show that these methods have additional contributions and can be extended to: (i) tests for a change in persistence, (ii) partial sums tests of cointegration and (iii) tests for changes in dynamic volatility models. The significance of these methods is demonstrated via the consistency of the long-run variance estimator which scales the change-point statistics, the asymptotic properties of the tests, their finite sample performance and their relevance in empirical applications and policy analysis. The second objective is threefold: First, to show that ignoring structural changes in financial time series yields biased and inconsistent risk management (Value at Risk, VaR and Excess Shortfall, ES) estimates and consequently leads to investment misallocations. Second, to propose methods for evaluating the stability of financial time series sequentially or on-line which can be used as a quality control procedure for financial risk management as well as to show that monitoring implied volatilities yields early warning indicators of a changing risk structure. Moreover we show that model averaging in the presence of structural breaks as well as other model uncertainties involved in risk management estimates, can provide robust estimates of VaR and ES. New results are derived on the optimal weights for model averaging in the context of dynamic volatility models and asymmetric loss functions. Third, we propose a novel way to construct prediction-based change-point statistics that reduce the detection delay of existing sequential tests and provide a probability about the likelihood of a structural change.

517 200 €

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

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

944 940 €

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

Late Pleistocene/early Holocene Europe is said to be the ideal laboratory for the investigation of human responses to rapidly changing climates and environments, migration and adaptation. Yet, pinpointing precisely how and why contemporaneous Final Palaeolithic/earliest Mesolithic (15,000-11,000 years BP) foragers migrated, and which environmental or other factors they adapted to – or failed to – has remained remarkably elusive. At the core of ClioArch is the radical but, in light of research-historical insights, necessary hypothesis that the current archaeological cultural taxonomy for this iconic period of European prehistory is epistemologically flawed and that operationalisations and interpretations based on this traditional taxonomy – especially those that seek to relate observed changes in material culture and land-use to contemporaneous climatic and environmental changes – are therefore problematic. Hence, novel approaches to crafting the taxonomic building blocks are required, as are novel analyses of human|environment relations in this period. ClioArch’s premier ambition is to provide operational cultural taxonomies for the Final Palaeolithic/earliest Mesolithic of Europe and to couple these with interdisciplinary cultural evolutionary, quantitative ecological methods and field archaeological investigations beyond the state-of-the-art, so as to better capture such adaptations – almost certainly with major implications for the standard culture-historical narrative relating to this period. In so doing, the project will pioneer a fully transparent and replicable – and eminently transferable – methodology for the study of the impacts of climate change and extreme environmental events in deep history. In turn, such a quantitative understanding of past adaptive dynamics will position archaeology more centrally in contemporary debates about climate change, environmental catastrophe and their cultural dimensions.

1 907 638 €

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

This project will investigate how the prominence of counting and computation transforms many of the assumptions, operations and outcomes of the law. It targets two types of computational law: artificial legal intelligence or data-driven law (based on machine learning), and cryptographic or code-driven law (based on blockchain technologies). Both disrupt, erode and challenge conventional legal scholarship and legal practice. The core thesis of the research is that the upcoming integration of computational law into mainstream legal practice, could transform the mode of existence of law and notably of the Rule of Law. Such a transformation will affect the nature of legal protection, potentially reducing the capability of individual human beings to invoke legal remedies, restricting or ruling out effective redress. To understand and address this transformation, modern positive law will be analysed as text-driven law, enabling a comparative analysis of text-driven, data-driven and code-driven normativity. The overarching goal is to develop a new hermeneutics for computational law, based on (1) research into the assumptions and (2) the implications of computational law, and on (3) the development of conceptual tools to rethink and reconstruct the Rule of Law in the era of computational law. The intermediate goals are an in-depth assessment of the nature of legal protection in text-driven law, and of the potential for legal protection in data-driven and code-driven law. The new hermeneutics will enable a new practice of interpretation on the cusp of law and computer science. The research methodology is based on legal theory and philosophy of law in close interaction with computer science, integrating key insights into the affordances of computational architectures into legal methodology, thus achieving a pivotal innovation of legal method.

2 492 433 €

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

Linked to terrorism, moral breakdown, and societal decay, Transnational Organised Crime (TOC) has come to embody current global anxieties as a figure of fear and cause of disquiet. Yet despite its central position on the social and political radar, our knowledge of it remains limited and fragmentary. Quantitative analyses may have identified the scale of the problem, but its underlying socio-cultural logic and practices remain under-researched and largely obscure. TOC is on the rise, and we need better insights into how it develops and expands, who engages in it and why, and how it is linked to and embedded in social networks that straddle countries and contexts. CRIMTANG proposes a unique approach to the study of the social infrastructure of contemporary TOC. It develops a research strategy that is ethnographic and transnational in design and so attuned to the human flows and formations of TOC. The project comprises a trans-disciplinary research team of anthropologists, criminologists and political scientists, and builds on their prior experience of the people, regions and languages under study. It explores the illegal and overlapping flows of migrants and drugs from North-West Africa into Europe, following a key trafficking trajectory stretching from Tangiers to Barcelona, Paris and beyond. In so doing, CRIMTANG sheds new light on the actual empirical processes in operation at different points along this trafficking route, whilst simultaneously developing new theoretical and methodological apparatuses for apprehending TOC that can be exported and applied in other regions and contexts. It reimagines the idea of social entanglement and proposes new transnational and collective fieldwork strategies. Finally, it will advance and consolidate the European research environment on TOC by creating a research hub for transnational ethnographic criminology at the University of Copenhagen.

1 999 909 €

Start date: 2018-02-01, End date: 2023-01-31

Evidence of a growing disengagement of citizens from politics is multiplying. Electoral turnout reaches historically low levels. Anti-establishment and populist parties are on the rise. Fewer and fewer Europeans trust their representative institutions. In response, we have observed a multiplication of institutional reforms aimed at revitalizing representative democracy. Two in particular stand out: the delegation of some political decision-making powers to (1) selected citizens and to (2) selected experts. But there is a paradox in attempting to cure the crisis of representative democracy by introducing such reforms. In representative democracy, control over political decision-making is vested in elected representatives. Delegating political decision-making to selected experts/citizens is at odds with this definition. It empowers the non-elected. If these reforms show that politics could work without elected officials, could we really expect that citizens’ support for representative democracy would be boosted and that citizens would re-engage with representative politics? In that sense, would it be a cure for the crisis of representative democracy, or rather a curse? Our central hypothesis is that there is no universal and univocal healing (or harming) effect of non-elected politics on support for representative democracy. In order to verify it, I propose to collect data across Europe on three elements: (1) a detailed study of the preferences of Europeans on how democracy should work and on institutional reforms towards non-elected politics, (2) a comprehensive inventory of all actual cases of empowerment of citizens and experts implemented across Europe since 2000, and (3) an analysis of the impact of exposure to non-elected politics on citizens’ attitudes towards representative democracy. An innovative combination of online survey experiments and of panel surveys will be used to answer this topical research question with far-reaching societal implication.

1 981 589 €

Start date: 2018-09-01, End date: 2023-08-31

Somatically acquired loss-of-heterozygosity (LOH) is extremely common in cancer; deletions of recessive cancer genes, miRNAs, and regulatory elements, can confer selective growth advantage, whereas deletions over fragile sites are thought to reflect an increased local rate of DNA breakage. However, most LOHs in cancer genomes remain unexplained. Here we plan to combine a TALEN technology and the experimental models of cell transformation derived from primary human cells to delete specific chromosomal regions that are frequently lost in cancer samples. The development of novel strategies to introduce large chromosomal rearrangements into the genome of primary human cells will offer new perspectives for studying gene function, for elucidating chromosomal organisation, and for increasing our understanding of the molecular mechanisms and pathways underlying cancer development.Using this technology to genetically engineer cells that model cancer-associated genetic alterations, we will identify LOH regions critical for the development and progression of human cancers, and will investigate the cooperative effect of loss of genes, non-coding RNAs, and regulatory elements located within the deleted regions on cancer-associated phenotypes. We will assess how disruption of the three-dimensional chromosomal network in cells with specific chromosomal deletions contributes to cell transformation. Isogenic cell lines harbouring targeted chromosomal alterations will also serve us as a platform to identify compounds with specificity for particular genetic abnormalities. As a next step, we plan to unravel the mechanisms by which particular homozygous deletions contribute to cancer-associated phenotypes. If successful, the results of these studies will represent an important step towards understanding oncogenesis, and could yield new diagnostic and prognostic markers as well as identify potential therapeutic targets.

1 498 764 €

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

The project seeks to study the role of digital media in the shaping of transnational memories on disappearance. It investigates a novel case that is in process of shaping: the disappearance of 43 students in Mexico in September 2014. The role of the new media in getting citizens’ attention and in marking a “turning point” was crucial to the upsurge of a counter-movement against the Mexican government and qualifies the event as significant for the transnational arena. The groundbreaking aspect of the project consists in proposing a double approach: a) a theoretical approach in which “disappearance” is considered as a particular crime that becomes a model for analyzing digital memory. Disappearance is a technology that produces a subject with a new ontological status: the disappeared are non-beings, because they are neither alive nor dead. This ontological status transgresses the clear boundaries separating life and death, past, present and future, materiality and immateriality, personal and collective spheres. “Digital memory”, i.e. a memory mediated by digital technology, is also determined by the transgression of the boundaries of given categories b) a multidisciplinary approach situating Mexico´s case in a long transnational history of disappearance in the Hispanic World, including Argentina and Spain. This longer history seeks to compare disappearance as a mnemonic object developed in the global sphere –in social network sites as blogs, Facebook, Twitter and YouTube– in Mexico and the social performances and artistic representations –literature, photo exhibitions, and films– developed in Spain and Argentina. The Mexican case represents a paradigm for the redefinition of the relationship between media and memory. The main output of the project will consist in constructing a theoretical model for analyzing digital mnemonic objects in the rise of networked social movements with a transnational scope.

1 444 125 €

Start date: 2016-07-01, End date: 2021-06-30

"DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. In cancer increased aberrant DNA methylation is believed to work as a silencing mechanism for tumor suppressor genes such as INK4A, RB1 and MLH1. The high frequency of abnormal DNA methylation found in cancer might be due to the inactivation of a proofreading and/or fidelity system regulating the correct patterns of DNA methylation. Currently we have very limited knowledge about such mechanisms. In this research proposal, we will focus on elucidating the biological function of a novel protein family, which catalyzes the conversion of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC). By catalyzing this reaction the TET proteins most likely work as DNA demethylases, and they might therefore have a role in regulating DNA methylation fidelity. Interestingly, accumulated data has in the last 2 years shown that TET2 is one of the most frequently mutated genes in various hematological cancers. We propose to investigate the molecular mechanisms by which TET2 regulates normal hematopoiesis, how its inactivation leads to hematopoietic malignancies and how the protein contributes to the regulation of DNA methylation patterns and transcription. Furthermore, we propose several experimental approaches for identifying proteins required for the recruitment of TET proteins to target genes and to analyze their role in the regulation of DNA methylation patterns and in cancer. Finally, we will investigate the potential functional role of 5-hmC and explore the potential mechanisms by which this modification could be erased. We expect to provide new insights into the biology of DNA methylation, hydroxymethylation and contribute to unravel the roles of TET proteins in normal physiology and cancer."

2 298 000 €

Start date: 2012-07-01, End date: 2017-06-30

Human rights are under pressure, in Europe as elsewhere, due to several developments, namely [1] War on terror: the pressures generated by competing discourses [2] Coping with the dangers of rights inflation [3] Conflicting rights: how to handle rights as contested claims [4] The challenges of dealing with universality under fire In this context, the human rights leadership of the European Court of Human Rights is of crucial importance. Yet the Court is not fit for purpose. Inconsistencies and sloppy legal reasoning undermine both its credibility and the impact of its decisions. The research programme that I propose will strengthen the consistency and persuasiveness of Court s legal reasoning so as to improve its accountability and transparency. My aim is to identify new technical solutions for important human rights problems, by the development and application of creative methodologies. The substantive innovations within the field of European human rights law that I propose to make are: [a] the development of new legal tools, which will consistently integrate the accommodation of the particularities of non-dominant groups into the reasoning of the European Court of Human Rights [b] the development of a new theoretical framework combining minimum and maximum approaches to human rights protection, followed by its translation into clear legal criteria for use by the European Court of Human Rights [c] the development of a script that will enable the adoption of a consistent approach by the European Court of Human Rights to conflicts between human rights My methodological approach is characterized by the combination of empirical and normative dimensions, a 360° comparison, and the integration of qualitative research methods (interviews and focus groups with key stakeholders).

1 370 000 €

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

Dynamic interplay between histone modifications and DNA methylation defines the chromatin structure of the humane genome and serves as a conceptual framework to understand transcriptional regulation in normal development and human disease. The ultimate goal of this research proposal is to study the chromatin architecture during normal and malignant T cell differentiation in order to define how DNA methylation drives oncogenic gene expression as a novel concept in cancer research. T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric and 25% of adult ALL cases and was originally identified as a highly aggressive tumor entity. T-ALL therapy has been intensified leading to gradual improvements in survival. However, 20% of pediatric and 50% of adult T-ALL cases still relapse and ultimately die because of refractory disease. Research efforts have unravelled the complex genetic basis of T-ALL but failed to identify new promising targets for precision therapy. Recent studies have identified a subset of T-ALLs whose transcriptional programs resemble those of early T-cell progenitors (ETPs), myeloid precursors and hematopoietic stem cells. Importantly, these so-called ETP-ALLs are characterized by early treatment failure and an extremely poor prognosis. The unique ETP-ALL gene expression signature suggests that the epigenomic landscape in ETP-ALL is markedly different as compared to other genetic subtypes of human T-ALL. My project aims to identify genome-wide patterns of DNA methylation and histone modifications in genetic subtypes of human T-ALL as a basis for elucidating how DNA methylation drives the expression of critical oncogenes in the context of poor prognostic ETP-ALL. Given that these ETP-ALL patients completely fail current chemotherapy treatment, tackling this completely novel aspect of ETP-ALL genetics will yield new targets for therapeutic intervention in this aggressive haematological malignancy.

958 750 €

Start date: 2015-07-01, End date: 2020-06-30

"The first part of this project is about employment in Europe, including the new members of the European Union. Both the level of employment and the type of jobs created will be examined. A thorough study of institutional structures and policies is proposed, with a view to arriving at conclusions about their influence on job creation and about the best policy needed to achieve national or European-level employment objectives. Job creation is investigated at the two-digit level and male and female employment, wage inequality and the role of policy will be studied in depth. The research will build on solid theoretical microfoundations taking into account the choices available to firms and workers/consumers about working at home or in the market and buying domestic or foreign goods. The project has a second part about unemployment, with special emphasis on recession. The same emphasis on institutions and policies as for employment is given to this part. A key component of the project is new theory on the evolution of institutions and policies in markets with friction, and on the impact that the policy changes that took place after the recession of the 1980s have had on the responses of European labour markets to the recent recession. Special attention will be given to the formerly planned economies and the reasons for their slow convergence to the western economies."

2 200 143 €

Start date: 2013-06-01, End date: 2018-05-31

"Alignment and argument structure lies at the heart of all current theoretical models in linguistics, both syntactic models and research within typology. In spite of that, no large-scale comprehensive study of the historical development of case marking and argument structure has been carried out in modern times, using modern linguistic approaches and frameworks, and covering an entire language family from its first documentation until modern times. The project EVALISA aims to investigate case marking and argument structure from a historical perspective, or more precisely non-nominative case marking of subjects, focusing on its development through the history of the Indo-European languages. One of the products emerging from the project is an electronically searchable database of predicates taking non-nominative subject marking, available to the research community at large, for further research on the topic. Another product is a typology of grammaticalization paths of non-nominative case marking of subjects. This is a timely enterprise given that non-nominative subject marking is extremely common in the languages of world. A third product is a methodology for reconstructing syntax and grammar, based on the tools of Construction Grammar. The theoretical framework of Construction Grammar is easily extendible to syntactic reconstruction, due to the basic status of form–meaning pairings in that model, and hence the more lexicon-like status of the grammar. This creates a natural leap for Construction Grammar from synchronic form–meaning pairings to historical reconstruction, based on form–meaning pairings. This methodology is of importance for scholars within anthropological linguistics, working on the history of oral or less-documented languages."

1 498 744 €

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

This five-year project aims to generate a paradigm shift in the understanding of Graeco-Roman and Late Antique communication. Non-literary, ‘documentary’ texts from Ancient Egypt such as letters, petitions and contracts have provided and continue to provide a key witness for our knowledge of the administration, education, economy, etc. of Ancient Egypt. This project argues that since documentary texts represent originals, their external characteristics should also be brought into the interpretation: elements such as handwriting, linguistic register or writing material transmit indirect social messages concerning hierarchy, status, and power relations, and can therefore be considered ‘semiotic resources’. The project’s driving hypothesis is that communicative variation – variation that is functionally insignificant but socially significant (e.g. there are ~ there’s ~ it’s a lot of people) – enables the expression of social meaning. The main aim of this project is to analyse the nature of this communicative variation. To this end, a multidisciplinary team of six researchers (one PI, one post-doc, and four PhD’s) will apply recent insights form socio-semiotic and socio-linguistic theory to a corpus of Graeco-Roman and Late Antique documentary texts (I – VIII AD) by means of a three-level approach: (i) an open-access database of annotated documentary texts will be created; (ii) the ‘semiotic potential’ of the different semiotic resources that play a role in documentary writing will be analysed; (iii) the interrelationships between the different semiotic resources will be studied. The project will have a significant scientific impact: (i) it will be the first to offer a holistic perspective towards the ‘meaning’ of documentary texts; (ii) the digital tool will open up new ways to investigate Ancient texts; (iii) it will make an important contribution to current socio-semiotic and socio-linguistic research; (iv) it will provide new insights about humans as social beings.

1 476 250 €

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

"Financial economics is at a crossroads: Academics are struggling to redefine the theory of finance and practitioners and regulators to restructure the financial industry. The current financial crisis will have significant impact on how we regulate financial markets and how we manage risk in companies and financial institutions. It will continue to inspire an intense discussion and research agenda over the next decade in academics, in industry, and among financial regulators and a central focus will be the role of frictions in financial markets. Nowhere are these issues more pertinent than in Europe right now. To take up the challenge presented by this crossroad of financial economics, my research project seeks to contribute to the knowledge of financial frictions and what to do about them. FRICTIONS will explore how financial frictions affect asset prices and the economy, and the implications of frictions for financial risk management, the optimal regulation, and the conduct of monetary policy. Whereas economists have traditionally focused on the assumption of perfect markets, a growing body of evidence is leading to a widespread recognition that markets are plagued by significant financial frictions. FRICTIONS will model key financial frictions such as leverage constraints, margin requirements, transaction costs, liquidity risk, and short sale constraints. The objective is to develop theories of the origins of these frictions, study how these frictions change over time and across markets, and, importantly, how they affect the required return on assets and the economy. The project will test these theories using data from global equity, bond, and derivative markets. In particular, the project will measure these frictions empirically and study the empirical effect of frictions on asset returns and economic dynamics. The end result is an empirically-validated model of economic behavior subject to financial frictions that yields qualitative and quantitative insights."

1 307 160 €

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

There has been a dramatic increase in interest in commons in the last 10 to 15 years, from traditional commons managing the use of exhaustible natural resources by fixed numbers of people within natural borders, to global information commons, dealing with non-rival, non-excludible goods by a potentially limitless number of unknown users. The emerging global genetic-resource commons fits somewhere in between, shifting in the direction of information commons as digital-information infrastructures allow physically distributed collections to be networked in virtual global pools. In this research project we propose that networking pools of genetic resources in a global commons potentially is a workable alternative to proprietary market-based solutions, which have been shown to be unable to generate sufficient investment in the vast quantities of genetic resources that are neglected because of their unknown and/or unlikely commercial value. These neglected resources are the building blocks for future scientific research and have enormous value for sustaining biodiversity and livelihoods in developing and industrialized countries. Our hypothesis is that implementing collective intellectual property strategies and standard material transfer agreements for access to these pre-competitive research materials has become feasible in a cost effective manner through new hybrid approaches to governance which combine design features from natural resource commons and digital information commons. To substantiate these proposals, this research project will conduct a comparative institutional analysis of the use and exchange practices in the genetic-resource commons, and propose a set of governance arrangements that would put these practices on a sound legal and institutional basis.

1 041 600 €

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

Thoracic aortic aneurysm and dissection (TAAD) is an important cause of morbidity and mortality in the western world. As 20% of all affected individuals have a positive family history, the genetic contribution to the development of TAAD is significant. Over the last decade dozens of genes were identified underlying syndromic and non-syndromic forms of TAAD. Although mutations in these disease culprits do not yet explain all cases, their identification and functional characterization were essential in deciphering three key aortic aneurysm/dissection patho-mechanisms: disturbed extracellular matrix homeostasis, dysregulated TGFbeta signaling and altered aortic smooth muscle cell contractility. Owing to the recent advent of next-generation sequencing technologies, I anticipate that the identification of additional genetic TAAD causes will remain quite straightforward in the coming years. Importantly, in many syndromic and non-syndromic families, significant non-penetrance and both inter- and intra-familial clinical variation are observed. So, although the primary genetic underlying mutation is identical in all these family members, the clinical spectrum varies widely from completely asymptomatic to sudden death due to aortic dissection at young age. The precise mechanisms underlying this variability remain largely elusive. Consequently, a better understanding of the functional effects of the primary mutation is highly needed and the identification of genetic variation that modifies these effects is becoming increasingly important. In this project, I carefully selected four different innovative strategies to discover mother nature’s own modifying capabilities in human and mouse aortopathy. The identification of these genetic modifiers will advance the knowledge significantly beyond the current understanding, individualize current treatment protocols to deliver true precision medicine and offer promising new leads to novel therapeutic strategies.

1 987 860 €

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

Not only does the writer’s hand hold the pen, it manipulates pictures as well. Writers touch, hoard, cut, copy, pin and paste various kinds of pictures and these actions integrate literature in visual culture in many ways that have never been tackled as a whole before. Some writers spent their life surrounded by pictures taken from magazines, creating an inspirational environment; yet others nurtured their imagination with touristic leaflets and visual advertisements; others created fictional characters based on collected portraits. What do writers do with pictures? How does literature stage the pictures handled? From very concrete and banal uses of pictures will emerge a new vision of literature as intermediality in action. This investigation applies the tool set of visual anthropology and visual studies to writers for a deeper understanding of visual ecosystems. Covering a large period, from the beginning of mass reproduction in the 1880s and the digital practices of today, HANDLING focuses on the French and French-speaking field and stands as a laboratory to refashion a broader model for relationships between image and text. Its main challenge is to get to the root of contemporary iconographic practices. HANDLING is unconventional because literary studies usually focus on the text: contrary to the norm, it sets the image at the very centre of the literary act. This approach might yield promising results for the visibility of literature in the future, especially in exhibitions. Making these practices visible will make literature itself more visible. As an internationally recognized specialist of text-image relationships with an in-depth knowledge of French/Belgian literature and photography, I will build a team and lead this 5-year ambitious project. Grounded in interdisciplinarity, it will show the significant and unexpected role of literature in material visual culture.

1 500 000 €

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

Mimesis is one of the most influential concepts in Western thought. Originally invoked to define humans as the “most imitative” creatures in classical antiquity, mimesis (imitation) has recently been at the centre of theoretical debates in the humanities, social sciences, and the neurosciences concerning the role of “mimicry,” “identification,” “contagion,” and “mirror neurons” in the formation of subjectivity. And yet, despite the growing confirmations that imitation is constitutive of human behaviour, mimesis still tends to be confined to the sphere of realistic representation. The HOM project combines approaches that are usually split in different areas of disciplinary specialization to provide a correction to this tendency. Conceived as a trilogy situated at the crossroads between literary criticism, cinema studies, and critical theory, HOM’s outcomes will result in two monographs and accompanying articles that explore the aesthetic, affective, and conceptual implications of the mimetic faculty. The first, radically reframes a major proponent of anti-mimetic aesthetics in modern literature, Oscar Wilde, by looking back to the classical foundations of theatrical mimesis that inform his corpus; the second considers the material effects of virtual simulation by looking ahead to new digital media via contemporary science-fiction films; and the third establishes an interdisciplinary dialogue between philosophical accounts of mimesis and recent discoveries in the neurosciences. Together, these new perspectives on homo mimeticus reconsider the aesthetic foundations of a major literary author, open up a new line of inquiry in film studies, and steer philosophical debates on mimesis in new interdisciplinary directions.

1 044 000 €

Start date: 2016-11-01, End date: 2021-10-31

This ERC program addresses an unsettled political science problem, namely how does the shifting of policymaking competencies to higher levels of government affect the opportunities of societal interests to seek representation. On this issue two completely different theoretical expectations exist. One the one hand, the Madisonian view entails that shifting competencies upwards is a healthy antidote to the powers of specific interests that may dominate smaller polities. Multi-levelness may also provide political opportunities as it enables actors to make strategic venue shifts when they are unable to attract the necessary attention at one venue. On the other hand, shifting policymaking upwards may seriously restrict the opportunities for diffuse interests, undermine encompassing forms of interest representation, and increase the barriers for local groups to gain attention. Instead of creating opportunities for all, multi-layered systems may decrease opportunities and reproduce or reinforce representational bias. One of the reasons why the implications of multi-layeredness are so poorly understood is the fact that political science has not developed a proper understanding of what representational bias means; some scholars see bias in terms of mobilization, while others conceive it in terms of the strategic interactions between organized interests and policymakers. This ERC program will integrate theoretically, methodologically and empirically these different aspects of group politics, by taking explicitly into account the nature of multi-layered systems. The innovative character of it lies in the theoretical combination of mapping interest group community dynamics, with a more nuanced characterization of organizational form and an in-depth investigation of bias in terms of strategies.

1 655 263 €

Start date: 2014-09-01, End date: 2019-08-31

Anti-cancer immunotherapy has provided patients with a promising treatment. Yet, it has also unveiled that the immunosuppressive tumor microenvironment (TME) hampers the efficiency of this therapeutic option and limits its success. The concept that metabolism is able to shape the immune response has gained general acceptance. Nonetheless, little is known on how the metabolic crosstalk between different tumor compartments contributes to the harsh TME and ultimately impairs T cell fitness within the tumor. This proposal aims to decipher which metabolic changes in the TME impede proper anti-tumor immunity. Starting from the meta-analysis of public human datasets, corroborated by metabolomics and transcriptomics data from several mouse tumors, we ranked clinically relevant and altered metabolic pathways that correlate with resistance to immunotherapy. Using a CRISPR/Cas9 platform for their functional in vivo selection, we want to identify cancer cell intrinsic metabolic mediators and, indirectly, distinguish those belonging specifically to the stroma. By means of genetic tools and small molecules, we will modify promising metabolic pathways in cancer cells and stromal cells (particularly in tumor-associated macrophages) to harness tumor immunosuppression. In a mirroring approach, we will apply a similar screening tool on cytotoxic T cells to identify metabolic targets that enhance their fitness under adverse growth conditions. This will allow us to manipulate T cells ex vivo and to therapeutically intervene via adoptive T cell transfer. By analyzing the metabolic network and crosstalk within the tumor, this project will shed light on how metabolism contributes to the immunosuppressive TME and T cell maladaptation. The overall goal is to identify druggable metabolic targets that i) reinforce the intrinsic anti-tumor immune response by breaking immunosuppression and ii) promote T cell function in immunotherapeutic settings by rewiring either the TME or the T cell itself.

1 999 721 €

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

"The study of Africa as a region ""peripheral"" to mainstream Islamic studies helps a deeper understanding of the cultural dynamics of Islam. While North African Islam has been subject to extensive research, the Muslim cultures of sub-Saharan Africa have received relatively little attention; most of it paid to West African regions. This project will contribute to both African and Islamic studies by producing for the first time a critical evaluation of textual witnesses of Islamic culture in the Horn of Africa (esp. Eritrea, Ethiopia, Djibouti, Somaliland) and therefore considerably contribute to the change in the state-of-the-art in both Islamic and African studies. The comparative study will be the first to assess simultaneously types and contents of texts, their transmission history, and the role they (as well as the respective authors and copyists) have played in the culture and identity formation in both the Horn of Africa and the “heartland” Islamic countries. Both Arabic texts as well as those written in local languages (using Arabic alphabet: ajami) will be considered, allowing an evaluation of linguistic and cultural influences. A reevaluation of the external Islamic sources dealing with these areas will complete the picture. Competences in philology, history, manuscript studies, linguistics and computer science will be merged in producing a Digital Research Environment for North-East African Islam. More than a corpus of centrally collected data, it will include images accompanied by searchable descriptive metadata, digital text editions, bibliography as well as an open access database for quantitative and qualitative comparative analysis of text and documentary corpora as well as their linguistic and graphic features will serve as a tool for the project and as a basis for future research. The research findings will provide a deeper understanding of Muslim thought and proselytism, and the effects Islam has had on society."

1 550 200 €

Start date: 2013-07-01, End date: 2018-12-31

The project presents an economic history and socio-cultural reconstruction of Japan in the age of the great depression; it is an attempt to demonstrate the depression's 'total' or multicontextual implications by outlining different but complimentary views of what was defined as the depression's core problems (and their possible solutions) within different social classes and within different strands of thought. Seen in historical perspective, it covers the period from the 'ShMwa financial crisis' (1927) until the outbreak of the second Sino-Japanese War (1937). The project consists out of three components: First, it addresses the macro-economic ideas in vogue at the time. It specifically concentrates on the personalities and roles of finance ministers Inoue Junnosuke • –K© and especially Takahashi Korekiyo ØK/ ('Japan's Keynes'), who has widely been credited for smoothening the role of the global depression on the Japanese economy. The second part of the project rests with the origins of depression in Japan's official and semi-official colonies in 1927 and the role the latter played in fueling the later crisis on the Japanese mainland. The project investigates the role of speculation, and inquires to which degree the effects of depression were 'imported' from the subsidiary economies of Taiwan, the Korean peninsula, and Manchuria. Third, as this project has a strong focus on the role economic realities were identified ('semantics'), it also develops a cultural history of the age of depression. The project identifies the rise of a new vocabulary and discourse in an era obsessed with the idea of an economic and moral dead end (ikizumari).

549 442 €

Start date: 2009-10-01, End date: 2014-09-30

The magnificent Kongo kingdom, which arose in the Atlantic Coast region of Equatorial Africa, is a famous emblem of Africa’s past. It is an important cultural landmark for Africans and the African Diaspora. Thanks to its early introduction to literacy and involvement in the Trans- Atlantic trade, the history of this part of sub-Saharan Africa from 1500 onwards is better known than most other parts. Nevertheless, very little is known about the origins and earlier history of the kingdom. Hence, this grant application proposes an interdisciplinary approach to this question. Archaeology and historical linguistics, two key disciplines for early history reconstruction in Africa, will play the most prominent role in this approach. Paradoxically, if the wider region of the Kongo kingdom is one of the best documented areas of Central Africa from a historical and ethnographic point of view, it is virtually unknown archaeologically. The proposed research team will therefore undertake pioneer excavations in several capital sites of the old kingdom. Similarly, no comprehensive historical study has covered the languages of the Kongo and closely affiliated kingdoms. Nonetheless, the earliest documents with Bantu data, going back to the early 16th century, originate from this region. The proposed research team will therefore undertake a historical-comparative study of the Kikongo dialect cluster and surrounding language groups, such as Kimbundu, Teke and Punu-Shira, systematically comparing current-day data with data from the old documents. Special attention will be given to cultural vocabulary related to politics, religion, social organization, trade and crafts, which in conjunction with the archaeological discoveries, will shed new light on th

1 400 760 €

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

The key concern of the proposed research is how political power is established and reproduced through the production of the fundamental social contracts of property and citizenship. We will re-define the research on so-called failed and weak states, by examining what political authority is actually exercised rather than measuring how they fall short of theoretical ideals. In developing countries with legal and institutional pluralism, no single institution exercises the political authority as such. Different institutions compete to define and enforce rights to property and citizenship. This is most visible at the local level, yet it has implications for theorizing the state as such. Hence, investigating the social production of property and citizenship is a way to study state formation. We study local institutions that exercise political authority and govern access to resources, and recognition of these rights. What institution guarantees what claims as rights, and, especially, how, is crucial, as it leads to the recognition of that particular institution as a political authority. We therefore study statutory as well as non-statutory institutions. We are not simply looking for property deeds and passports etc. issued by statutory government as measurements of political authority. Rather, we look for secondary forms of recognition ‘issued’ by non-statutory institutions that represent mutual acknowledgements of claims even without a narrow legal endorsement. Dynamics such as these are fundamental for a concise understanding of developing country state formation processes. Ten country studies with rural and urban field sites will be conducted. We focus on concrete controversies. We collect data at several levels and from different sources, including resident groups, land users, local civil servants, local politicians and business-owners, as well as large-scale contractors, municipal politicians and administrators.

2 469 285 €

Start date: 2016-01-01, End date: 2020-12-31

"There are noticeable asymmetries in availability of high-quality natural language processing (NLP). We can adequately summarize English newspapers and translate them into Korean, but we cannot translate Korean newspaper articles into English, and summarizing micro-blogs is much more difficult than summarizing newspaper articles. This is a fundamental problem for modern societies, their development and democracy, as well as perhaps the most important research problem in NLP right now. Most NLP technologies rely on highly accurate syntactic parsing. Reliable parsing models can be induced from large collections of manually annotated data, but such collections are typically limited to sampled newswire in major languages. Highly accurate parsing is therefore not available for other languages and other domains. The NLP community is well aware of this problem, but unsupervised techniques that do not rely on manually annotated data cannot be used for real-world applications, where highly accurate parsing is needed, and sample bias correction methods that automatically correct the bias in newswire when parsing, say, micro-blogs, do not yet lead to robust improvements across the board. The objective of this project is to develop new learning methods for parsing natural language for which no unbiased labeled data exists. In order to do so, we need to fundamentally rethink the unsupervised parsing problem, including how we evaluate unsupervised parsers, but we also need to supplement unsupervised learning techniques with robust methods for automatically correcting sample selection biases in related data. Such methods will be applicable to both cross-domain and cross-language syntactic parsing and will pave the way toward robust and scalable NLP. The societal impact of robust and scalable NLP is unforeseeable and comparable to how efficient information retrieval techniques have revolutionized modern societies."

1 126 183 €

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

The broad aim of this research program is to understand how markets get created, how they evolve, and how specific market organizations affect economic outcomes. It combines theoretical and empirical analyses of specific markets and includes the development of new methods to map theory to data and vice versa. Each market provides a concrete ground to explore the broad questions the project addresses and motivates a distinct set of questions. The first class of markets the research will consider are financial markets. These can be viewed as the archetype of large markets where prices play the main role in the allocation. The focus there will on market creation, market evolution and the process of competition. The second class of markets the research will consider are allocation mechanisms where prices do not play a role in the allocation, making efficiency hard to obtain. The focus there will be on strategic manipulation of preferences by participants, their consequences on outcomes and possible remedies. Together, these markets will contribute to our understanding of how market rules affect outcomes and performance, to what extent laissez-faire evolution fosters efficient market organizations, and when and how public intervention can help generate better market organizations.

840 000 €

Start date: 2008-09-01, End date: 2014-02-28

The extracellular matrix (ECM) is known to play a critical role in driving cancer progression, and yet we lack knowledge of its composition and structure. The goal of my ERC project is to investigate how alterations in biochemical composition and structural properties of the ECM during cancer progression impact on cell behaviour to drive metastasis, which is responsible for over 90% of cancer patient deaths. In order to do this, my lab has developed a method to in situ decellularise organs leaving structurally intact ECM scaffolds for subsequent analysis or for repopulation to study cell-ECM interactions in situ. We have deployed our method to decellularise primary tumour and metastatic organs in mice bearing orthotopic breast cancer tumours for subsequent quantitative global mass spectrometry (MS) proteomics, spatio-structural mapping of ECM components in 3D, and live imaging of repopulated cells. We observed fundamental alterations in ECM composition and structure between normal and tumour, and primary and metastatic tissue. We have selected two ECM components specifically upregulated in metastatic organs for subsequent validation. We discovered a marked decrease in proteins associated with fibrillogenesis in metastatic organs and will investigate the impact of this on metastatic ECM stiffness. We will decellularise organs from transgenic mouse models of breast and pancreatic cancer, at specific stages during cancer progression to determine the evolution of global ECM composition and structure, and how this impacts on cell behaviour through functional perturbation. Finally, we shall validate relevance of findings to human disease through use of human cancer lines and analysis of human patient samples. The research proposed will provide ground-breaking insight into how the ECM regulates cellular behaviour during normal and pathological conditions, and will test new strategies to combat metastasis that could be translated into the clinic to benefit cancer patients.

1 997 500 €

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

Metastatic growth of cancer cells requires extracellular matrix (ECM) production. The current understanding is that transcription factors regulate ECM production and thus metastatic growth by increasing the expression of collagen prolyl 4-hydroxylase (CP4H). In contrast, we recently discovered that metabolism regulates CP4H activity independently of the known transcription factors. Specifically, we found that loss of pyruvate metabolism inhibits CP4H activity and consequently ECM–dependent breast cancer cell growth. Based on this discovery we propose the novel concept that metabolism regulates metastatic growth by increasing ECM production. In this project we will investigate the following questions: 1) What is the mechanism by which pyruvate regulates CP4H activity in breast cancer cells? To address this question we will investigate pyruvate metabolism and ECM production in 3D cultures of various breast cancer cell lines using 13C tracer analysis, metabolomics, and two-photon microscopy based ECM visualization. 2) How can this novel metabolic regulation be exploited to inhibit breast cancer-derived lung metastases growth? To address this question we will inhibit pyruvate metabolism in metastatic breast cancer mouse models using genetically modified cells and small molecules in combination with immuno- and chemotherapy. 3) How can this novel regulation be translated to different metastatic sites and cancers of different origin? To address this question we will determine the in vivo metabolism of breast cancer-, lung cancer-, and melanoma-derived liver and lung metastases (using metabolomics and 13C tracer analysis), and link it to ECM production (using two-photon microscopy based ECM visualization). With this project we will deliver a novel concept by which metabolism regulates metastatic growth. In a long-term perspective we expect that targeting this novel metabolic regulation will pave the way for an unexplored approach to treat cancer metastases.

2 000 000 €

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

Mind-Bending Grammars examines change in mental grammars of 17th century individuals across their lifespan as attested in their writings. The project treats grammar as a self-organizing network of form-meaning schemas continuously fine-tuning itself, where activating one schema may prime formally or functionally associated ones. In analyzing multiple grammar changes in healthy adults it aspires to make a breakthrough in the cognitive modelling of grammar, and is expected to bear on views of cognitive plasticity and self-organizing systems (e.g. ecosystems). To reach these goals it will determine (i) how change in one part of an individual’s grammar relates to change in another; (ii) to what extent grammar change in individuals is possible and attested beyond childhood. This is still unsettled. Formal models hold that change occurs in language acquisition, social ones that it mainly results from adult interaction. The first ignore too much adult usage, the second grammar as a system. Seven cases are examined: i. Progressive (I’m loving it) ii. Future [going to] (he’s going to love it) iii-iv. (Pseudo)clefts (it’s Eve he loves) v. Rare passives (Eve was sent for) vi. Subject-raising (he’s said to be nice) vii. New copulas (get/grow hot) Each case changes much in the 17th century, warranting separate study. Yet the changes may also be linked. Formally, going to for example started as a progressive, and this may have resulted in sustained mutual influence. Functionally all but the last may be responses to changing word order. Until c1500 time adverbs (THEN ran he), focal elements (EVE loves he) or empty subjects (THEY say he’s nice) could precede the verb. After, this position got restricted to subjects that are topics (HE ran). Progressives need no time adverbs, clefts move the focal element, and passivization/subject-raising align topic & subject; all of this helped to realize the new order. Grow & get are unassociated to other cases, and serve as a control group.

1 208 025 €

Start date: 2015-09-01, End date: 2020-08-31

The negative employment and social developments across Europe since the start of the crisis, coupled with increased fiscal constraints and changing migration patterns, have led to increasing depictions of EU and third-country immigrants as ‘abusers’ of their social protection systems. Member States have accordingly sought reduce migrants’ ability to access social protection benefits, despite the fact that they are disproportionately at risk of poverty and social exclusion. This project looks at the different strategies that migrants have to access social protection within (post) crisis Europe and does so by explicitly integrating social policy and migration studies’ approaches on the phenomenon. More precisely, it aims to study transnational social protection, that we define as migrants’ cross-border strategies to cope with social risks in areas such as health, long-term care, pensions or unemployment that combine entitlements to host and home state-based public welfare policies and market-, family- and community-based practices. This study thus consists in, first, identifying the social protection policies and programs that home countries make accessible to their citizens abroad, and then compiling this information into an online database. We will then aggregate the results of the database into a Transnational Social Protection Index (TSPIx) in order to determine the overall level of engagement of each state with citizens abroad in a comparative way. Second, on the basis of the results of the index, we will select case studies of migrants from two EU and two non-EU countries that vary in their level of engagement in providing social protection to their citizens abroad. We will then undertake multi-sited ethnographic fieldwork to qualitatively assess the informal social protection strategies used by migrants and examine their interaction with formal host and home state social protection provision.

1 306 718 €

Start date: 2016-11-01, End date: 2021-10-31

MMS-II pursues the hypothesis that the Mamluk sultanate was a cultural product constructed in the interaction between state formation and historiography. MMS-II follows up from the ERC-project MMS' focus on the social production of power networks in the Syro-Egyptian sultanate between the 1410s and 1460s, but it does so by directing the themes of political history and Arabic historiography towards entirely new, unexplored horizons. Current understanding of the late medieval Middle East continues to rely heavily on the rich Arabic historiographical production of the period. However, the particular nature, impact and value of this highly politicized historiography remains hugely underexplored and underestimated. MMS-II aims to remedy this, by arguing with and beyond instead of against or outside of this historiography’s subjectivities. It wants to understand its texts as products of particular socio-cultural practices and, at the same time, as a particular type of actors in such practices. Analytically, state formation will be prioritised as one extremely relevant patterned set of effects of such practices. Heuristically, the project will focus on practices related to claims of historical truth and order, asking how Arabic historiographical texts written between the 1410s and the 1460s related to the regularly changing social orders that were produced around the different sultans of these decades. My main hypothesis is that of these texts' active participation in the construction of a particular social memory of one longstanding sultanate of military slaves (‘Mamlukisation’). MMS-II has three specific objectives: the creation of a reference tool for Arabic historiographical texts from the period 1410-1470; the in-depth study of particular sets of these texts; the analysis of political vocabularies in these texts. By thus exploring the inter-subjective re/production of Arabic historiography MMS-II will generate a welcome cultural turn in late medieval Islamic history.

2 000 000 €

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

The mind is not an unitary entity, nor is its physical substrate, the brain. Both can be divided into multiple components, some of which have been referred to as modules. Many controversies exist in cognitive science, psychology, and philosophy about the properties and the status of these modules. A compromise view is offered by an hypothesis of modularization which has two central tenets: (i) Genetic influences determine a weak non-modular organization of the mind and (ii) this map develops into a set of module-like compartments. Here we will test this hypothesis in the domain of visual object knowledge. Testable predictions are derived from a novel extension and integration of previous proposals (i) for the presence of non-modular maps (Op de Beeck et al., 2008, Nature Rev. Neurosci.), which are logical candidates for the starting point proposed in the modularization hypothesis, and (ii) for how maps might be transformed by further experience (Op de Beeck & Baker, 2010, Trends in Cognit. Sci.) into a strong compartmentalization for specific types of visual stimuli. We will determine whether the same rules govern modularization for face perception and reading, despite the very different evolutionary history of faces and word stimuli. We will apply well-known analysis tools from the psychology literature, such as multidimensional scaling, to the patterns of activity obtained by brain imaging, so that we can directly compare the structure and modularity of visual processing in mental space with the structure of “brain space” (functional anatomy). The combined behavioral and imaging experiments will characterize the properties of non-modular maps and module-like regions in sighted and congenitally blind adults and in children, and test specific hypotheses about how experience affects non-modular maps and the degree of modularization. The findings will reveal how the structure of the adult mind is the dynamic end point of a process of modularization in the brain.

1 474 800 €

Start date: 2012-06-01, End date: 2017-05-31

Making Sense of Games (MSG) will build a methodology for the humanistic study of games, and develop a theory of how ludic meaning is produced. Following the pervasive, global growth of video gaming culture and the games industry, the multi-disciplinary field of game studies has grown exponentially in the last 15 years, with numerous new journals, conferences, university programs and research departments. However, still lacking at this ‘adolescent’ stage of the field’s development are game-specific methods and theoretical foundations necessary to train researchers and build curricula. In aesthetic games research there is not yet any widely accepted methodology for game analysis, and there has not yet been any large-scale, long-term attempt to produce a theoretical platform that can support and advance the field. MSG aims to fill this gap by combining fundamental hermeneutic approaches (semiotics, reception theory, reader response, theories of representation, narrative theory) with recent theories of ludic structure (game ontology) into a hermeneutic theory of game meaning, which can be used as a set of tools and concepts for game analysis and criticism. MSG will be a triple first for aesthetic game research: a five-year research program, a hermeneutic theory of games, and a team-based effort to build an interdisciplinary methodology. The results from MSG will speak to many of the current public concerns and debates about games, such as gamer culture, games’ cultural and artistic status, the representation of minorities, misogyny, violence and even addiction. MSG will demonstrate the strong usefulness of humanistic approaches not only to game studies itself, but also to the 21st century’s most vibrant new cultural sector. It will also provide other aesthetic fields (literary studies, film studies, art history) with theoretical models, critical insights, and a rich empirical material for comparative exploration.

2 006 906 €

Start date: 2016-11-01, End date: 2021-10-31

Today’s ecological crisis prompts us to rethink our attitude towards physical and natural realities that have traditionally been seen as opposed to human subjectivity and agency. What emerges from this “non-human turn” is a sense of our interdependence on things like the bacteria in our intestines or the carbon atoms supporting life on Earth. Ecological theorist Timothy Morton uses the metaphor of the “mesh” to express this idea of human/non-human interconnectedness. This project will map the formal and thematic strategies through which contemporary narrative practices engage with the non-human and envisage this interconnectedness. Storytelling is an indispensable tool for making sense of experience by establishing temporal and causal relations. But it is also biased towards the human-scale realities of action and social interaction. How can narrative overcome this bias? How does it convey phenomena that challenge our belief in the ontological and material self-sufficiency of the human? Comparing fictional narratives in print (novels and short stories) and conversational storytelling, we will systematically explore the ways in which narrative can forge connections across levels of reality, weaving together the human and the non-human into a single plot. The assumption is that narrative is a field where fictional practices are in constant dialogue with the stories told in everyday conversation—and with the culture-wide beliefs and concerns those stories reflect. Through its three sub-projects, the proposed research charts this complex dialogue while greatly advancing our understanding of how stories can be used to heighten people’s awareness of the mesh and its significance. The project builds on a combination of methods (close readings of novels, qualitative analysis of interviews), aiming to open up a new field of study at the intersection of literary scholarship and the social sciences—with narrative theory serving as a catalyst for the interdisciplinary exchange.

1 130 000 €

Start date: 2017-02-01, End date: 2022-01-31

In folk psychology and in bioethical discussions, the central dogma of genetics is often taken for granted: humans are seen as defined in a genetic blueprint. The conceptualization of psychiatric conditions as innate or acquired, biological or psychosocial, genetic or environmental, influences the ascription of both capacity responsibility (the capacity to adapt or adjust one’s own behavior) and normative responsibility of individuals or the society towards those diagnosed. But findings in the field of epigenetics indicate that the social and physical environment influence how genes are expressed. Indeed, epigenetics may shed a new light on distinctions such as innate/acquired, genetic/environmental, biological/psychosocial: a far more complex view on neurodevelopmental disorders may emerge, with ethical implications. However, the implications of epigenetics for discussions on the scope and extent of normative responsibility have not been adequately addressed. NEUROEPIGENETHICS aims to investigate the ethical implications of epigenetics for neurodevelopmental disorders. We will use theoretical and empirical methods to investigate how certain concepts (innate/biological/genetic) affect the ways in which professionals and stakeholders (persons with a neurodevelopmental disorder and their families) conceive of responsibility. We will evaluate how the emerging field of epigenetics alters the ascription of capacity responsibility and normative responsibility. We will research how individuals with Autism Spectrum Disorder (ASD), Tourette Syndrome (TS) and Attention Deficit Hyperactivity Disorder (ADHD)and their families experience the interaction between their condition and their biological and social environment. Finally, we will define moral responsibility in light of the emerging field of epigenetics in the area of neurodevelopmental disorders and child psychiatric practice.

1 453 012 €

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

Metabolic adaptations in central carbon metabolism play a key role in cancer. Yet, the success of therapeutic interventions in major pathways has been limited, although some of the changes have been known to exist for almost 100 years. Biochemical textbooks present intermediary metabolism as something canonical, and the molecular identity of most enzymes required for the production of known intermediary metabolites is indeed known. Yet, the function of many putative enzymes is still unknown, indicating that novel metabolic pathways containing so far unknown metabolites exist. We have recently discovered a novel metabolic pathway containing two metabolites that have never been described before. Preliminary data indicate that this pathway might play an important role in a group of cancers sharing specific mutations. Furthermore, genetic inactivation of a component of this pathway in mice is compatible with normal development, indicating that pharmacological inhibition should be well tolerated. In the present project, we will use a multi-dimensional approach combining biochemical, genetic and pharmacological techniques, to identify missing components of this metabolic pathway and assess its role in cellular metabolism and cancer development. In the process of this, we will develop tools that will allow us to test whether this pathway can be targeted in vivo. Thus, our work will lead to the description of a novel metabolic pathway, should reveal novel regulatory circuits and might open novel therapeutic avenues in cancer and beyond.

1 989 103 €

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

"The novel is today the most popular literary genre worldwide. Its early history has not been written yet. In order to enhance our understanding of this history (both conceptually and cross-culturally), this project offers the first comprehensive reconstruction and interpretation of the persistence of ancient novelistic material in hagiographical narrative traditions in the Mediterranean in Late Antiquity and the early Middle Ages (4th-12th cent.). This period constitutes a blind spot on the radar of scholars working on the history of the novel, who conceptualize it, much to the detriment of the study of narrative in subsequent periods, as an ‘empty’ interim period between the latest ancient representatives of the genre (ca. 3rd-4th cent.) and its re-emergence in 11th/12th-century Byzantium and 11th-century Persia. This project, on the other hand, advances the hypothesis that different hagiographical traditions throughout Late Antiquity and the early Middle Ages were impacted (directly or indirectly) by ancient novelistic influences of different kinds and adopted, rehearsed, re-used and adapted them to various degrees as tools for the representation of saints as heroes/heroines. In this sense, constructions of heroism in these traditions should be understood to varying degrees as ‘novelistic’ and raise crucial issues about fictionalization and the texts’ own implicit conceptualizations of fiction. Three stages of the project will test different aspects of this hypothesis. Firstly, the project will chart for the first time all novelistic influences in the hagiographical corpus texts. Secondly, it will analyze the impact of these influences on constructions of heroism in specific hagiographical traditions (mainly Latin, Greek and Syriac Martyr Acts, hagiographical romances and saints’ Lives) and examine implications for notions of fictionalization and/or strategies for enhancing verisimilitude and authenticity. Finally, diachronic and cross-cultural dimensions of the research hypothesis will be articulated through the study of continuity of hagiographical traditions (and their constructions of heroism) in narrative genres from the 11th and 12th centuries in the West (medieval romance), Byzantium (novels) and the East (Persian romance). By generating an improved understanding of the impact of ancient novelistic material in different hagiographical traditions throughout Late Antiquity and the early Middle Ages, this project aims to contribute not just to the history of the idea of fiction but also to the study of hagiography, the early history of the novel and to all disciplines that study these literary genres."

1 467 300 €

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

Several sophisticated image processing circuits have been discovered in the animal retina, many of which manifest massive neural synchrony. A major insight is that this type of synchrony often translates to high-frequency activity on a macroscopic level, but electroretinography (ERG) has not been tapped to examine this potential in humans. Bolstered by our compelling results combining ERG with magnetoencephalography (MEG), this project will address several open questions with respect to human visual processing: 1) Could variable retinal timing be linked to intrinsic image properties and pass on phase variance downstream to visual cortex? Our data suggests the retina responds to moving gratings and natural imagery with non-phase-locked high gamma oscillations (>65 Hz) just like visual cortex, and that slower ERG potentials exhibit strong phase-locking within stimuli but large phase variance across stimuli. 2) Do such retinal gamma band responses, both evoked and induced, directly drive some cortical gamma responses? Pilot data suggests that it can, through retinocortical coherence, our novel ERG-MEG mapping technique. 3) Several kinds of motion have now been shown to elicit massive synchrony in mammalian retina circuits. Does this also result in macroscopic high-frequency activity? If so, our experiments will finally reveal and characterize motion detection by the human retina. 4) Do efferent pathways to the retina exist in humans? We discovered that the ERG exhibits eyes-closed alpha waves strikingly similar to the classic EEG phenomenon and, leveraging our retinocortical coherence technique, that this activity is likely driven by contralateral occipital cortex. Then, can retinal responses be influenced by ongoing cortical activity? Characterizing retinocortical interaction represents a complete paradigm shift that will be imperative for our understanding of neural synchrony in the human nervous system and enable several groundbreaking new avenues for research.

1 499 850 €

Start date: 2016-03-01, End date: 2021-02-28

Bone development and homeostasis must incontestably rely on a correct spatial positioning of osteoblasts to generate bone at appropriate sites. A failure of osteoblasts to reach the sites in need of bone formation may contribute to impaired fracture repair and osteoporosis. Conversely, uncontrolled osteogenic cell movement may play a role in diseases involving aberrant placement of bone. Mechanisms of osteoblastic migration and adhesion may even be mimicked by bone-metastasizing tumor cells. Yet, the trafficking of osteogenic cells has been a largely neglected aspect in bone biology. My recent studies abroad for the first time shed light on this process in vivo. Newly generated transgenic mouse models for osteoblast lineage tracing revealed that specifically osteoprogenitors, and not mature osteoblasts, moved to initiate novel sites of bone formation. Intriguingly, osteoprogenitors entered developing and healing bones along with their neovascularization, some being wrapped as pericytes around the blood vessels, suggesting an unprecedented vessel-guided cell movement mechanism. Implementing these concepts and models, I here propose two angles to elucidate the mechanisms mediating osteoprogenitor motility. In a first approach, we will assess the involvement, in vitro and in vivo, of known candidate molecular targets of (i) cell-matrix interactions pivotal in cell migration, (ii) cell-cell adhesion, and (iii) the association between pericytes and endothelial cells. Secondly, a high-risk high-gain reverse approach using innovative technologies aims to identify the specific genetic profiles of motile osteoprogenitors and bone-anchored mature osteoblasts. Overall this project will bring novel mechanistic insight in osteogenic cell movement in bone biology and pathology, and add to our broader understanding of cell migration and progenitor properties. The potential to evoke new therapies to widespread skeletal pathologies underscores the study’s importance and high impact.

1 499 200 €

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

This research explores the impact of property regimes on experiences of citizenship across five democratic countries: Greece, The Netherlands, Spain, the United Kingdom and the United States. Property rights are a foundational element of democracy, but the right to private property exists in tension with values of equality and a right to shelter. An investigation of property is urgent given the recent normalisation of economic models that have resulted in millions of evictions every year. Through an ethnographic study of eviction this research provides a comparative analysis of the benefits and limitations of contemporary property regimes for democratic citizenship. A property regime is defined as the combination of moral discourses about real landed property with the regulatory policies and market mechanisms that shape the use, sale and purchase of property. The selected countries represent a diverse set of property regimes, but all five are experiencing a housing and eviction crisis that has created new geographies of disadvantage, exacerbated inequalities of race, gender, age and income, and led to social unrest. Building on the PI's previous research into citizen-driven democratic innovation, this research critically examines the concept of property through a novel methodology dubbed 'conflictive context construction' that employs a qualitative approach centred on moments of conflict resulting from the use, sale or purchase of specific properties to answer: how do property regimes shape people's experience of citizenship and what can this tell us about the role of property in contemporary models of democratic governance? The high gain of this research lies in the opportunity to rethink the role of property within democracy based on extensive empirical data about how moral assumptions combine with particular ways of regulating and marketing property to exacerbate, alleviate or create inequalities within contemporary experiences of democratic citizenship.

1 970 688 €

Start date: 2018-09-01, End date: 2023-08-31

The objective of PhilAnd is to conduct a large-scale exploration of how, and under which form, philosophy appeared for the first time in al-Andalus. This issue is pivotal to understanding the history of sciences and ideas, and the role of the Arab-Muslim world in this transfer to Medieval Europe. Its relevance today also lies in the fact that it addresses questions of cultural and religious identities, since the formative stage of philosophy in al-Andalus proved decisive in shaping the intellectual background of many later authors from the Peninsula, whether Muslims, Jews, or Christians. At the crossroads of major lines of enquiries in scholarship and in line with recent discoveries having important chronological implications, PhilAnd focuses on the 10th century, a period usually disregarded by historians on the assumption that philosophy as such was not cultivated in the Iberian Peninsula before the 11th-12th centuries. Its originality is also to put emphasis on ‘ill-defined’ materials and channels of transmission, a field which remains largely unexplored. This project consists of five topics designed for highly-specialised scholars, and of another three transversal types of exploration conducted in the form of conferences convened with leading experts in the world. The final objectives are to test the hypothesis: 1) that the emergence of philosophy in al-Andalus significantly predates the currently accepted time; and 2) that the impact of this formative stage was considerably wider than commonly acknowledged. This project also seeks to provide a better evaluation of the originality of the first Andalusī philosophers with respect to their Oriental forerunners. This cutting-edge investigation is likely to stimulate major changes in our perception of how this primeval stage of philosophy in al-Andalus determined the subsequent developments of rational speculation among the three monotheistic communities of the Peninsula and the intellectual formation of Europe.

2 495 335 €

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