ERC FUNDED PROJECTS

Dramatic migrations in the third millennium BC re-shaped Europe, modifying its economy, society, ethnicity and ideological structure for ever. The best incentive proxy are populations that moved from the steppes of Russia, spreading as far west as Hungary, implanting a pastoral economy with widespread innovations. These dynamic people covered thousands of kilometres within a few centuries, and organised direct physical relations over the steppes for the first time. This synchronism is promoted by a society organised to fit to this lifestyle, with new herding techniques, likely use of wagons and domesticated horses, and a protein-rich diet, whose adaptive advantages are evident from the physical record in human skeletons and territorial extensions. This is the Yamnaya complex, whose impact remains visible today in the European gene pool and apparently the propagation of Indo-European languages. This international and interdisciplinary project examines the data from 320 excavated burial mounds and c.1350 burials to calibrate these changes, also against a control sample of supposedly local and neighbouring populations. The archaeological, biological and environmental information allows large, new datasets to be built, whose systematic interrogation and modelling should reveal the formative processes behind these changes. Assessing funeral archaeology, material culture, and exchange pattern defines their culture and impact. Scientific analyses of skeletons expose relations of origin, degrees of consanguinity, diet, and histories of individual mobility over single lifetimes with new precision and replicability. They should also act as proxy datasets for environmental changes using further analytical techniques in a context of landscape evolution. Diachronic patterns within these sets should link with aspects of the internal social dynamics, such as the creation of new status positions, visible later in the Pan-European Corded Ware and Bell Beaker groups.

2 494 209 €

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

YouCitizen is a comparative, multi-level ethnographic research project that examines the efforts of international organisations, civil society organisations, and states to foster citizenship for youth in divided societies. In their efforts, agents working in such organisations often engage in paradoxical, if not contradictory, acts to promote both cosmopolitanism within civil society and national identities, even when aspects of national identity have been a source of division. A central premise of the research is that the outcomes of these efforts are conditioned by the contexts in which programmes for youth are delivered and enacted. In these contexts – which include histories of division and marginalisation, societal and communal norms, family histories, and the spaces of daily life – youth interpret and experience citizenship. YouCitizen’s critical intervention is in extending the examination of citizenship formation to consider the ways in which youth interpret, experience, and potentially remake citizenship that is different to, and may actually challenge, the forms of citizenship that organisations and states attempt to instil. The empirical foci of the study are the networks of organisations promoting citizenship and/or civic engagement, and youth, aged 15-24 in South Africa, Bosnia-Herzegovina and Lebanon who have been involved with those programmes. It explores the goals of those organisations, their funding sources and activities to understand both the vision of citizenship they promote and the traditions and influences from which they draw; particular attention is paid to ideals and values associated with cosmopolitanism vis-à-vis the nation and the ways in which they address social division. Interviews and participant observation with youth explore the ways in which their experiences and understanding of citizenship are influenced by those programmes, but are also entwined with daily life in their homes and communities.

2 419 013 €

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

"Paul Ehrlich was the first scientist to postulate that if a compound could be made that selectively targeted disease-causing cells, then this agent could be used for the delivery of a toxin, which would enable a pharmacotherapy of unprecedented potency and selectivity. With this procedure, a ""magic bullet"" (Zauberkugel, his term for an ideal therapeutic agent) would be created, that killed diseased cells while sparing normal tissues. The concept of a ""magic bullet"" was to some extent realized by the invention of monoclonal antibodies, as these molecules provide a very specific binding affinity to their cognate target. However, monoclonal antibodies used as single agents are typically not able to induce cures for cancer or chronic inflammatory diseases. More recently, intense academic and industrial research activities have aimed at “arming” monoclonal antibodies with drugs or cytokines, in order to preferentially deliver these therapeutic payloads to the site of disease. Unfortunately, in most cases, ""armed"" antibody products still cause unacceptable toxicities, which prevent escalation to potentially curative dose regimens. In this Project, I outline a therapeutic strategy, which relies on the use of extremely specific tumor targeting agents, for the selective delivery of payloads, which can be conditionally activated at the site of disease. Methodologies for the conditional generation of active payloads include the stepwise non-covalent assembly of cytokines and the controlled release of cytotoxic drugs at suitable time points after injection, when the concentration of therapeutic agent in normal organs is acceptably low. Response to therapy will be profiled using innovative proteomic methodologies, based on HLA-peptidome analysis. Pharmaceutical agents with “activity on demand” hold a considerable potential not only for the therapy of cancer, but also for the treatment of other serious diseases, including certain highly debilitating chronic inflammatory condition"

2 000 000 €

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

The vascular system is a complex network of blood vessels that transports gases, nutrients and hormones throughout the organism. Most blood vessels that form during development and growth arise by the sprouting of new capillaries from pre-existing vessels, a process termed angiogenesis. An imbalance in angiogenesis contributes to the pathogenesis of numerous disease states: insufficient angiogenesis limits tissue recovery in ischemic disease, whereas stimulation of angiogenesis by cancer cells promotes tumor vascularization and growth. Angiogenesis inhibitors are already in clinical use for anti-tumor therapy; however, multiple reports of resistance are calling for the identification of additional targets. Furthermore, vascular malformations are a significant cause of morbidity and mortality. While the genetic basis for some vascular malformations is known, many genetic factors, including modifiers that affect the age-of-onset and severity of phenotypes, remain to be identified. Identifying modifier genes is important not only to fully assess genetic risk, but also to provide novel targets for therapy; however, identifying modifier genes has proven challenging. We recently uncovered a novel and simple way to identify modifier genes. By investigating gene and protein expression differences between knockout (mutant) and knockdown (antisense treated) zebrafish embryos, we found that mutations in specific genes, including some encoding angiogenic factors, lead to the upregulation of compensating (i.e., modifier) genes while knocking down these same genes does not. We hypothesize that the modifier genes identified through this approach in zebrafish also play important roles in humans. Thus, we will use this simple strategy to identify new genes that regulate vascular formation and homeostasis, and subsequently analyze their function in zebrafish as well as in mammalian models, as they are likely to play key roles in vascular development and disease.

2 500 000 €

Start date: 2016-10-01, End date: 2021-09-30