ERC FUNDED PROJECTS

This project aims at a better understanding of the philosophical richness of ninth century thought using the unprecedented and highly innovative method of the synchronic approach. The hypothesis directing this synchronic approach is that studying together in parallel the four main philosophical traditions of the century – i.e. Latin, Greek, Syriac and Arabic – will bring results that the traditional enquiry limited to one tradition alone can never reach. This implies pioneering a new methodology to overcome the compartmentalization of research which prevails nowadays. Using this method is only possible because the four conditions of applicability – comparable intellectual environment, common text corpus, similar methodological perspective, commensurable problems – are fulfilled. The ninth century, a time of cultural renewal in the Carolingian, Byzantine and Abbasid empires, possesses the remarkable characteristic – which ensures commensurability – that the same texts, namely the writings of Aristotelian logic (mainly Porphyry’s Isagoge and Aristotle’s Categories) were read and commented upon in Latin, Greek, Syriac and Arabic alike. Logic is fundamental to philosophical enquiry. The contested question is the human capacity to rationalise, analyse and describe the sensible reality, to understand the ontological structure of the world, and to define the types of entities which exist. The use of this unprecedented synchronic approach will allow us a deeper understanding of the positions, a clear identification of the a priori postulates of the philosophical debates, and a critical evaluation of the arguments used. It provides a unique opportunity to compare the different traditions and highlight the heritage which is common, to stress the specificities of each tradition when tackling philosophical issues and to discover the doctrinal results triggered by their mutual interactions, be they constructive (scholarly exchanges) or polemic (religious controversies).

1 998 566 €

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

The emergence of life is one of the most fascinating and yet largely unsolved questions in the natural sciences, and thus a significant challenge for scientists from many disciplines. There is growing evidence that ribonucleic acid (RNA) polymers, which are capable of genetic information storage and self-catalysis, were involved in the early forms of life. But despite recent progress, RNA synthesis without biological machineries is very challenging. The current project aims at understanding how to synthesize RNA in abiotic conditions. I will solve problems associated with three critical aspects of RNA formation that I will rationalize at a molecular level: (i) accumulation of precursors, (ii) formation of a chemical bond between RNA monomers, and (iii) tolerance for alternative backbone sugars or linkages. Because I will study problems ranging from the formation of chemical bonds up to the stability of large biopolymers, I propose an original computational multi-scale approach combining techniques that range from quantum calculations to large-scale all-atom simulations, employed together with efficient enhanced-sampling algorithms, forcefield improvement, cutting-edge analysis methods and model development. My objectives are the following: 1 • To explain why the poorly-understood thermally-driven process of thermophoresis can contribute to the accumulation of dilute precursors. 2 • To understand why linking RNA monomers with phosphoester bonds is so difficult, to understand the molecular mechanism of possible catalysts and to suggest key improvements. 3 • To rationalize the molecular basis for RNA tolerance for alternative backbone sugars or linkages that have probably been incorporated in abiotic conditions. This unique in-silico laboratory setup should significantly impact our comprehension of life’s origin by overcoming major obstacles to RNA abiotic formation, and in addition will reveal significant orthogonal outcomes for (bio)technological applications.

1 497 031 €

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

From medieval times, Arabic as well as European music was analysed in terms that were inherited from Classical Antiquity and had thus developed in a very different music culture. In spite of recent breakthroughs in the understanding of the latter, whose technicalities we access not only through texts and iconography, but also through instrument finds and surviving notated melodies, its relation to music traditions known from later periods and different places is almost uncharted territory. The present project explores relations between Hellenic/Hellenistic music as pervaded the theatres and concert halls throughout and beyond the Roman empire, Near Eastern traditions – from the diatonic system emerging from cuneiform sources to the flourishing musical world of the caliphates – and, as far as possible, African musical life south of Egypt as well – a region that maintained close ties both with the Hellenised culture of its northern neighbours and with the Arabian Peninsula. On the one hand, this demands collaboration between Classical Philology and Arabic Studies, extending methods recently developed within music archaeological research related to the Classical Mediterranean. Arabic writings need to be examined in close reading, using recent insights into the interplay between ancient music theory and practice, in order to segregate the influence of Greek thinking from ideas and facts that must relate to contemporaneous ‘Arabic’ music-making. In this way we hope better to define the relation of this tradition to the ‘Classical world’, potentially breaking free of Orientalising bias informing modern views. On the other hand, the study and reconstruction, virtual and material, of wind instruments of Hellenistic pedigree but found outside the confinements of the Hellenistic ‘heartlands’ may provide evidence of ‘foreign’ tonality employed in those regions – specifically the royal city of Meroë in modern Sudan and the Oxus Temple in modern Tajikistan.

775 959 €

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

Interferons (IFNs), which are signalling proteins produced by infected cells, are the first line of defence against viral infections. IFNs induce, in infected and neighbouring cells, the expression of hundreds of IFN-stimulated genes (ISGs). The ISGs in turn induce in cells a potent antiviral state, capable of preventing replication of most viruses, including Human Immunodeficiency Virus type 1 (HIV-1) and influenza A virus (FLUAV). Identifying the antiviral ISGs and understanding their mechanisms of action is therefore crucial to progress in the fight against viruses. ISGs playing a role in the antiviral state have been identified, such as human MX1, a well-known antiviral factor able to restrict numerous viruses including FLUAV, and MX2, an HIV-1 inhibitor. Both proteins bind to viral components but their detailed mechanisms of action, as well as the consequences of restriction on the activation of the innate immune system, remain unclear. Moreover, our preliminary work shows that additional anti-HIV-1 and anti-FLUAV ISGs remain to identify. In this context, this proposal seeks an ERC StG funding to explore 3 major aims: 1) unravelling the mechanisms of antiviral action of MX proteins, by taking advantage of their similar structure and engineered chimeric proteins, and by using functional genetic screens to identify their cofactors; 2) investigating the consequences of incoming virus recognition by MX proteins on innate immune signalling, by altering their expression in target cells and measuring the cell response in terms of gene induction and cytokine production; 3) identifying and characterizing new ISGs able to inhibit viral replication with a combination of powerful approaches, including a whole-genome CRISPR/Cas9 knock-out screen. Overall, this proposal will provide a better understanding of the molecular mechanisms involved in the antiviral effect of IFN, and may guide future efforts to identify novel therapeutic targets against major pathogenic viruses.

1 499 794 €

Start date: 2017-12-01, End date: 2022-11-30