ERC FUNDED PROJECTS

Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown. Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps. This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer

1 999 750 €

Start date: 2017-03-01, End date: 2022-02-28

The Acts of the Ecumenical Councils of Late Antiquity include (purportedly) verbatim minutes of the proceedings, a formal framework and copies of relevant documents which were either (allegedly) read out during the proceedings or which were later attached to the Acts proper. Despite this unusual wealth of documentary evidence, the daunting nature of the Acts demanding multidisciplinary competency, their complex structure with a matryoshka-like nesting of proceedings from different dates, and the stereotype that their contents bear only on Christological niceties have deterred generations of historians from studying them. Only in recent years have their fortunes begun to improve, but this recent research has not always been based on sound principles: the recorded proceedings of the sessions are still often accepted as verbatim minutes. Yet even a superficial reading quickly reveals widespread editorial interference. We must accept that in many cases the Acts will teach us less about the actual debates than about the editors who shaped their presentation. This does not depreciate the Acts’ evidence: on the contrary, they are first-rate material for the rhetoric of persuasion and self-representation. It is possible, in fact, to take the investigation to a deeper level and examine in what manner the oral proceedings were put into writing: several passages in the Acts comment upon the process of note-taking and the work of the shorthand writers. Thus, the main objective of the proposed research project could be described as an attempt to trace the destinies of the Acts’ texts, from the oral utterance to the manuscript texts we have today. This will include the fullest study on ancient transcript techniques to date; a structural analysis of the Acts’ texts with the aim of highlighting edited passages; and a careful comparison of the various editions of the Acts, which survive in Greek, Latin, Syriac and Coptic, in order to detect traces of editorial interference.

1 497 250 €

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

Amorphous and evolutionary DNA nanotechnology (AEDNA) explores novel conceptual directions and applications for DNA nanotechnology, which are based on intelligent, DNA-programmed soft hybrid materials, and the utilization of evolutionary principles for the optimization of nucleic acid nanocomponents. Amorphous DNA nanotechnology first aims at the creation of cell-sized, DNA-programmed microgels – DNA cells – with sensor, computation, communication, and actuator functions. Interacting DNA cells will be arranged into chemical cell consortia and artificial tissues using microfluidics, micromanipulation and 3D bioprinting techniques. Spatially distributed chemical circuits will then be utilized to establish collective behaviors such as quorum sensing, pattern formation, and self-differentiation within these consortia and tissues. The approach will be further scaled up to produce multicomponent DNA gel compositions that become active and differentiate upon mixing. In evolutionary nanotechnology, techniques derived from directed molecular evolution experiments will be applied to optimize the arrangement of functional nucleic acids on DNA and RNA nanoscaffolds. Compartmentalization and microfluidics will be utilized to screen for nucleic acid nanostructures capable of superstructure formation, and also for the development of ligand-sensitive components for molecular programming. An evolutionary approach will then be applied to amorphous DNA cells, resulting in DNA cell populations which contain individuals with different molecular identities. The proposal will pave the way for the creation of macroscopic materials with DNA-programmed intelligence, resulting in novel applications for DNA nanotechnology and molecular programming in diverse fields such as environmental and biological sensing, biocatalysis, smart adaptive materials, and soft robotics.

2 157 698 €

Start date: 2016-06-01, End date: 2021-05-31

This research will create a new theoretical vision of the importance of marriage as an agent of transformation in human sociality. Marriage globally is undergoing profound change, provoking intense debate and anxiety. These concerns refract wider instabilities in political, economic, and familial institutions. They signal the critical role of marriage in bringing together - and separating - intimate, personal, and familial life with wider state institutions. But we have little up to date comparative research or general theory of how marriage changes or the long-term significance of such change. Paradoxically, social scientific and public discourse emphasise the conservative and normative aspects of marriage. This underlines the need for a new theoretical frame that takes account of cultural and historical specificity to grasp the importance of marriage as both vehicle of and engine for transformation. AGATM overturns conventional understandings by viewing marriage as inherently transformative, indeed at the heart of social and cultural change. The research will investigate current transformations of marriage in two distinct senses. First, it will undertake an ethnographic investigation of new forms of marriage in selected sites in Europe, N. America, Asia, and Africa. Second, it will subject ‘marriage’ to a rigorous theoretical critique that will denaturalise marriage and reintegrate it into the new anthropology of kinship. Research on five complementary and contrastive sub-projects examining emerging forms of marriage in different locations will be structured through the themes of care, property, and ritual forms. The overarching analytic of temporality will frame the theoretical vision of the research and connect the themes. The resulting six monographs, journal articles, and exhibition will together revitalise the study of kinship by placing the moral, practical, political, and imaginative significance of marriage over time at its centre.

2 297 584 €

Start date: 2017-01-01, End date: 2022-06-30