ERC FUNDED PROJECTS

This project has the potential to radically change current understanding of cultic and social transformation in the post-exilic temple community of Jerusalem (c. 6th-4th centuries BCE), an important formative phase of ancient Judaism. “BABYLON” draws on recent, ground-breaking advances in the study of cuneiform texts to illuminate the Babylonian environment of the Judean exile, the socio-historical context which gave rise to the transformative era in Second Temple Judaism. In particular, these new data show that the parallels between Babylonian and post-exilic forms of cultic and social organization were substantially more far-reaching than presently recognized in Biblical scholarship. “BABYLON” will study the extent of these similarities and explore the question how Babylonian models could have influenced the restoration effort in Jerusalem. This goal will be achieved through four sub-projects. P1 will study the social dynamics and intellectual universe of the Babylonian priesthood. P2 will finalize the publication of cuneiform archives of Babylonian priests living in the time of the exile. P3 will identify the exact areas of change in the post-exilic temple community of Jerusalem. P4, the synthesis, will draw from each of these sub-projects to present a comparative study of the Second Temple and contemporary Babylonian models of cultic and social organization, and to propose a strategy of research into the possible routes of transmission between Babylonia and Jerusalem. The research will be carried out by three team members: the PI (P1 and P4), a PhD in Assyriology (P2) and a post-doctoral researcher in Biblical Studies specialized in the Second Temple period (P3 and P4). The participation of the wider academic community will be invited at two moments in the course of the project, in the form of a workshop and an international conference. “BABYLON” will adopt an interdisciplinary approach by bringing together Assyriologists and Biblical scholars for a much-needed dialogue, thereby exploding the artificial boundaries that currently exist in the academic landscape between these two fields.

1 200 000 €

Start date: 2009-09-01, End date: 2015-08-31

Systemic sclerosis (SSc) is an autoimmune disease that culminates in excessive extra-cellular matrix deposition (fibrosis) in skin and internal organs. SSc is a severe disease in which fibrotic events lead to organ failure such as renal failure, deterioration of lung function and development of pulmonary arterial hypertension (PAH). Together, these disease hallmarks culminate in profound disability and premature death. Over the past three years several crucial observations by my group changed the landscape of our thinking about the ethiopathogenesis of this disease. First, plasmacytoid dendritic (pDCs) cells were found to be extremely frequent in the circulation of SSc patients (1000-fold) compared with healthy individuals. In addition, we observed that pDCs from SSc patients are largely dedicated to synthesize CXCL4 that was proven to be directly implicated in fibroblast biology and endothelial cell activation, two events recapitulating SSc. Finally, research aimed to decipher the underlying cause of this increased pDCs frequency led to the observation that Runx3, a transcription factor that controls the differentiation of DC subsets, was almost not expressed in pDC of SSc patients. Together, these observations led me to pose the “SSc immune postulate” in which the pathogenesis of SSc is explained by a multi-step process in which Runx3 and CXCL4 play a central role. The project CIRCUMVENT is designed to provide proof of concept for the role of CXCL4 and RUNX3 in SSc. For this aim we will exploit a unique set of patient material (cell subsets, protein and DNA bank), various recently developed in vitro techniques (siRNA for pDCs, viral over expression of CXCL4/RUNX3) and apply three recently optimised experimental models (CXCL4 subcutaneous pump model, DC specific RUNX3 KO and the SCID/NOD/rag2 KO mice). The project CIRCUMVENT aims to proof the direct role for Runx3 and CXCL4 that could provide the final step towards the development of novel therapeutic targets

1 500 000 €

Start date: 2012-08-01, End date: 2017-07-31

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

2 227 326 €

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

"Communication between immune cells is crucial for regulating the magnitude and quality of immune responses. A newly uncovered means of intercellular communication involves transfer of small cell-derived vesicles. I recently discovered that vesicles released by immune cells are enriched for small noncoding RNAs, which may act as regulatory RNAs that can influence gene expression in vesicle-targeted cells. Furthermore, remarkable parallels emerged between RNAs abundantly present in cell-derived vesicles and a group of host RNAs specifically incorporated into retroviruses. These shared RNAs may underlie the formation or function of both cell-derived vesicles and retroviruses. Until now, mechanisms behind selective incorporation of small RNAs into cell-derived vesicles and their function in vesicle-targeted cells are poorly understood. Aim of INTERCOM: To resolve how the exchange of small RNAs via cell-derived vesicles contributes to intercellular communication between immune cells. Key objectives: 1. To determine the diversity and plasticity of the RNA content of vesicle subpopulations released by immune cells. 2. To explain functional differences between immune cell vesicle populations based on their RNA contents. 3. To determine the function of structural RNAs shared by immune cell-derived vesicles and retroviruses. Tools in virology research will be used in combination with several high-end technologies, which were uniquely adapted in my lab for vesicle-related research. These include a high-resolution flow cytometric method suited to analyze individual nano-sized vesicles, RNA deep sequencing with previously developed data analysis methods, and super-resolution microscopic imaging. The proposed work advances our understanding of communication processes in the immune system. This knowledge can be applied in defining vesicle RNA-based biomarkers for immune-related diseases and in designing genetically engineered cell-derived vesicles for therapeutic application."

1 499 806 €

Start date: 2013-11-01, End date: 2018-10-31