ERC FUNDED PROJECTS

Accurate determination of physical conditions of interstellar molecular clouds is a crucial step to better understand the life cycle of the interstellar matter and particularly the formation of stars and planets as well as the synthesis of organic molecules that may lead to emergence of life in the universe. A key parameter for the determination of these conditions from interstellar spectra is the calculation of accurate collisional rate coefficients of interstellar molecules with the most abundant species (H, He, H2 and e-). Whereas the knowledge of collisional processes has reached a certain level of maturity for collisions involving non-reactive molecules, very few reliable data exist for collisions involving reactive radicals and ions. The computation of such data is a real challenge since inelastic and reactive processes compete during collisions. In this project, we plan to overcome this complex problem and to provide collisional data for these radicals and ions in order to derive as much information as possible from the molecular spectra collected by current telescopes. As it is hardly possible to consider both collisional and reactive processes simultaneously, we will set up a new methodology based on quantum approach that allows obtaining accurate data. We will focus on molecular hydrides that are good candidates because of both their astrophysical importance and their quantum accessibility. We will carry out the determination of interaction potentials using quantum chemistry ab initio methods while the treatment of the dynamics of the nuclei will primarily be done using quantum time-independent reactive and non-reactive approaches. When exact quantum calculations will not be usable, innovative statistical quantum mechanical methods will also be explored. The new data will then be used in radiative transfer models and the predictions will be finally compared to observations in order to derive the abundances of reactive radicals with unprecedented accuracy.

1 802 625 €

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

The CRISPR-Cas system has been extensively studied for its ability to cleave DNA. In contrast, studies of the ability of the system to acquire and integrate new DNA from invaders as a form of prokaryotic adaptive immunity, have lagged behind. This delay reflects the extreme enthusiasm surrounding the potential of using the system’s cleavage capabilities as a genome editing tool. However, the enormous potential of the adaptation process can and should arouse a similar degree of enthusiasm. My lab has pioneered studies on the CRISPR adaptation process by establishing new methodologies, and applying them to demonstrate the essential role of the proteins and DNA elements, as well as the molecular mechanisms, operating in this process. In this project, I will establish novel platforms for studying adaptation and develop them into biotechnological applications and research tools. These tools will allow me to identify the first natural and synthetic inhibitors of the adaptation process. This, in turn, will provide genetic tools to control adaptation, as well as advance the understanding of the arms race between bacteria and their invaders. I will also harness the adaptation process as a platform for diversifying genetic elements for phage display, and for extending phage recognition of a wide range of hosts. Lastly, I will provide the first evidence for an association between the CRISPR adaptation system and gene repression. This linkage will form the basis of a molecular scanner and recorder platform that I will develop and that can be used to identify crucial genetic elements in phage genomes as well as novel regulatory circuits in the bacterial genome. Together, my findings will represent a considerable leap in the understanding of CRISPR adaptation with respect to the process, potential applications, and the intriguing evolutionary significance.

2 000 000 €

Start date: 2019-12-01, End date: 2024-11-30

During gametogenesis, germ cells undergo profound chromatin reorganisation, condensation and transcriptional shutdown. Upon fertilization, gamete chromatin is epigenetically reprogrammed, generating a totipotent zygote that can give rise to all cell types of the adult organism. The maternal factors that reprogram gametes to totipotency are unknown. The current dogma suggests that the parental epigenetic information must be erased in order to establish totipotency. In contrast, we have recently discovered that maternal gametes transmit the epigenetic H3K27me3 histone modification to the next generation (Zenk et al., Science, 2017) adding to increasing evidence suggesting that gametes convey more than just DNA to the offspring. Nevertheless, the underlying mechanisms and the impact of epigenetic inheritance through the gametes are not yet fully resolved. Critically, the mechanisms and impact of (i) paternal gamete reprogramming, (ii) paternal epigenetic inheritance and (iii) de novo establishment of the zygotic epigenome remain essentially unknown. The objective of this proposal is to unravel the fundamental principles underlying these three major epigenetic transitions in vivo in Drosophila. We will achieve our objective via three aims: (i) We will investigate the mechanisms underlying the reprogramming of sperm chromatin at fertilization. Specifically, we will determine the nature and extent of the contributions of two proteins essential for sperm chromatin reprogramming (ii) We will examine the mechanism of histone H3K27me3 inheritance through the paternal germline (iii) We will genetically dissect the de novo establishment of constitutive heterochromatin in the newly formed zygote. Our investigations of these epigenetic transitions are expected to reveal novel insights into the first steps in the formation of life, and to ultimately advance reproductive and regenerative medicine.

1 997 500 €

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

‘Almost three centuries later, it is past time to rethink Montesquieu’s holy trinity’ (Ackerman, 2010). As Ackerman (and many others) have observed, political reality has long left the traditional model of the separation of powers behind. The problems posed by this gap between constitutional theory and political practice have recently acquired fresh urgency as developments in Hungary, Poland, Turkey, Russia, the UK, US, Bolivia and elsewhere place the separation of powers under strain. These include the emergence of authoritarian leaders; personalisation of political authority; recourse to non-legal plebiscites; and the capture or de-legitimisation of other constitutional bodies. This project argues that these difficulties are rooted in a deeper problem with constitutional thinking about institutional power: a constitution-as-law approach that equates the conferral of legal power with the authority to exercise it. This makes it possible for a gap to emerge between legal accounts of authority and its diverse –and potentially conflicting (Cotterrell)– sociological foundations. Where that gap exists, the practical authority of an institution (or constitution) may be vulnerable to challenge from rival and more socially-resonant claims (Scheppele (2017)). It is this gap between legal norms and social facts that the project aims to investigate – and ultimately bridge. How is authority established? How is it maintained? How might it fail? And how does the constitution (as rule? representation (Saward)? mission statement (King)?) shape, re-shape and come to be shaped by those processes? By investigating these questions across six case studies, the project will produce a multi-dimensional account of institutional authority that takes seriously the sociological influence of both law and culture. The results from these cases provide the evidential foundation for the project’s final outputs: a new model and new evaluative measures of the separation of powers.

1 997 628 €

Start date: 2020-01-01, End date: 2024-12-31