ERC FUNDED PROJECTS

Sexual reproduction depends on the programmed induction of DNA double-strand breaks (DSBs) and their ensuing repair by homologous recombination. This complex process is essential for sexual reproduction because it ultimately allows the pairing and separation of homologous chromosomes during formation of haploid gametes. Although meiotic recombination has been investigated for decades, many of the underlying molecular processes remain unclear, largely due to the lack of biochemical studies. I have recently made important progress by, for the first time, successfully purifying proteins involved in two aspects of meiotic recombination: DSB formation and the final stage of formation of the crossovers that are a central raison-d’être of meiotic recombination. This has opened new avenues for future research that I intend to pursue in my own laboratory. Here, I propose a set of biochemical approaches, complemented by molecular genetics methods, to gain insights into four central problems: (i) How meiotic proteins collaborate to induce DSBs; (ii) How DSB proteins interact with components that form the axes of meiotic chromosomes; (iii) How proteins involved at later stages of recombination form crossovers; and (iv) How crossover proteins interact with components of synapsed chromosomes. For each problem, I will set up in vitro systems to probe the activities of the players involved, their interactions with DNA, and their assembly into macromolecular complexes. In addition, I propose to develop new methodology for identifying proteins that are associated with DNA that has undergone recombination-related DNA synthesis. My goal is to gain insights into the mechanisms that govern meiotic recombination. Importantly, these mechanisms are intimately linked not only to gamete formation, but also to the general recombination pathways that all cells use to maintain genome stability. In both contexts, our findings will be relevant to the development and avoidance of disease states.

1 499 075 €

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

This project proposes an analysis of the reconfigurations established in the socio-political vocabulary of the western Saharan region – southern Morocco, Western Sahara and Mauritania – from the “post-empire” to the contemporary period. The project should produce an analysis of 1) the social and political structures shared in the region, 2) the local variations of those structures, based on case studies, 3) their specific configurations, based on social markers such as gender, age, and class, 4) the use of those structures in different historical periods. All these will be under theoretical and ethnographic scrutiny in order to achieve its main goal: 5) to understand the recent articulation of the social and political structures of the Western Saharan region, with broader and often exogenous political vocabularies. The methodology used in this project is based on readings associated with different social sciences, with a particular focus on anthropology, history, and political science. The members of the research team, with experience and linguistic competence in the different geographies involved in this project, are expected to conduct original field enquiries, enabling a significant enhancement of the theoretical and ethnographic knowledge associated with this region. The project’s main goal is to analyse the types of interplay established between pre-modern socio-political traditions and contemporary political expression and activism, in a particularly sensitive – and academically disregarded – region. Its effort to integrate a context that is usually compartmentalized, as well as to put together a group of researchers generally “isolated” in their particular areas of expertise, geographies, or nations, should also be valued. The project’s results should enable the different contexts under study to be integrated into the wider maps of current scientific research, providing, at the same time a dissemination of its outputs to an extended audience.

1 192 144 €

Start date: 2017-04-01, End date: 2021-03-31

Genome stability relies on accurate partition of the genome during nuclear division. Proper mitosis, in turn, depends on changes in chromosome organization, such as chromosome condensation and sister chromatid cohesion. Despite the importance of these structural changes, chromatin itself has been long assumed to play a rather passive role during mitosis and chromosomes are usually compared to a “corpse at a funeral: they provide the reason for the proceedings but do not take an active part in them.” (Mazia, 1961). Recent evidence, however, suggests that chromosomes play a more active role in the process of their own segregation. The present proposal tests the “active chromosome” hypothesis by investigating how chromosome morphology influences the fidelity of mitosis. I will use innovative methods for acute protein inactivation, developed during my postdoctoral studies, to evaluate the role of two key protein complexes involved in mitotic chromosome architecture - Condensins and Cohesins. Using a multidisciplinary approach, combining acute protein inactivation, 3D-live cell imaging and quantitative methods, I propose to investigate the role of mitotic chromosomes in the fidelity of mitosis at three different levels. The first one will use novel approaches to uncover the process of mitotic chromosome assembly, which is still largely unknown. The second will explore how mitotic chromosomes take an active part in mitosis by examining how chromosome condensation and cohesion influence chromosome movement and the signalling of the surveillance mechanisms that control nuclear division. Lastly we will evaluate how mitotic errors arising from abnormal chromosome structure impact on development. We aim to evaluate, at the cellular and organism level, how the cell perceives such errors and how (indeed if) they tolerate mitotic abnormalities. By conceptually challenging the passive chromosome view this project has the potential to redefine the role of chromatin during mitosis.

1 492 000 €

Start date: 2015-10-01, End date: 2020-09-30

"In the past few decades, the disciplines of textual scholarship and genetic criticism have insisted on their respective differences. Nonetheless, a rapprochement would be mutually beneficial. The proposed research endeavours to innovate scholarly editing with the combined forces of these two disciplines. Since genetic criticism has objected to the subservient role of manuscript research in textual criticism, the proposed research suggests a reversal of roles: instead of employing manuscript research with a view to making an edition, an electronic edition can be designed in such a way that it becomes a tool for manuscript research and genetic criticism. The research hypothesis is that such a rapprochement can be achieved by means of an approach to textual variants that values creative undoing (ways of de-composing a text as an integral part of composition and literary invention) more than has hitherto been the case in textual scholarship. This change of outlook will be tested by means of the marginalia, notes and manuscripts of an author whose work is paradigmatic for genetic criticism: Samuel Beckett. His manuscripts will serve as a case study to determine the functions of creative undoing in the process of literary invention and its theoretical and practical implications for electronic scholarly editing and the genetic analysis of modern manuscripts. Extrapolating from this case study, the results are employed to tackle a topical issue in European textual scholarship. The envisaged rapprochement between the disciplines of genetic criticism and textual scholarship is the core of this proposal’s endeavour to advance the state of the art in these disciplines by giving shape to a new orientation within scholarly editing."

1 147 740 €

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