ERC FUNDED PROJECTS

With the advent of new sequencing technologies, population geneticists now have access to more data than ever before. We have access to thousands of human genomes from a diverse set of populations around the globe, and, thanks to advances in DNA extraction and library preparation, we now are beginning to have access to ancient DNA sequence data. These data have greatly improved our knowledge of human history, human adaptation to different environments and human disease. Genome-wide studies have highlighted many genes or genomic loci that may play a role in adaptive or disease related phenotypes of biological importance. With these collections of modern and ancient sequence data we want to answer a key evolutionary question: how do human adaptations arise? We strongly believe that the state-of-the-art methodologies for uncovering signatures of adaptation are blind to potential modes of adaptation because they are lacking two critical components – more complete integration of multiple population haplotype data (including archaic, ancient and modern samples), and an account of population interactions that facilitate adaptation. Therefore I plan to develop new methods to detect shared selective events across populations by creating novel statistical summaries, and to detect admixture-facilitated adaptation which we believe is likely a common mode of natural selection. We will apply these tools to new datasets to characterize the interplay of natural selection, archaic and modern admixture in populations in the Americas and make a comparative analysis of modern and ancient European samples to understand the origin and changing profile of adaptive archaic alleles. As a result our work will reveal evolutionary processes that have played an important role in human evolution and disease.

1 500 000 €

Start date: 2020-12-01, End date: 2025-11-30

Embedded Control software plays a critical role in many safety-critical applications. For instance, modern vehicles use interacting software and hardware components to control steering and braking. Control software forms the main core of autonomous transportation, power networks, and aerospace. These applications are examples of cyber-physical systems (CPS), where distributed software systems interact tightly with spatially distributed physical systems with complex dynamics. CPS are becoming ubiquitous due to rapid advances in computation, communication, and memory. However, the development of core control software running in these systems is still ad hoc and error-prone and much of the engineering costs today go into ensuring that control software works correctly. In order to reduce the design costs and guaranteeing its correctness, I aim to develop an innovative design process, in which the embedded control software is synthesized from high-level correctness requirements in a push-button and formal manner. Requirements for modern CPS applications go beyond conventional properties in control theory (e.g. stability) and in computer science (e.g. protocol design). Here, I propose a compositional methodology for automated synthesis of control software by combining compositional techniques from computer science (e.g. assume-guarantee rules) with those from control theory (e.g. small-gain theorems). I will leverage decomposition and abstraction as two key tools to tackle the design complexity, by either breaking the design object into semi-independent parts or by aggregating components and eliminating unnecessary details. My project is high-risk because it requires a fundamental re-thinking of design techniques till now studied in separate disciplines. It is high-gain because a successful method for automated synthesis of control software will make it finally possible to develop complex yet reliable CPS applications while considerably reducing the engineering cost.

1 470 800 €

Start date: 2019-02-01, End date: 2024-01-31

Biomolecules exist in an aqueous environment of dipolar water molecules and solvated ions. Their structure and biological function are strongly influenced by electric interactions with the fluctuating water shell and ion atmosphere. Understanding such interactions at the molecular level is a major scientific challenge; presently, their strengths, spatial range and interplay with other non-covalent interactions are barely known. Going far beyond existing methods, this project introduces the new paradigm of a direct time-resolved mapping of molecular electric forces on sub-nanometer length scales and at the genuine terahertz (THz) fluctuation frequencies. Vibrational excitations of biomolecules at the interface to the water shell act as sensitive noninvasive probes of charge dynamics and local electric fields. The new method of time resolved vibrational Stark shift spectroscopy with THz external fields calibrates vibrational frequencies as a function of absolute field strength and separates instantaneous from retarded environment fields. Based on this knowledge, multidimensional vibrational spectroscopy gives quantitative insight in the biomolecular response to electric fields, discerning contributions from water and ions in a site-specific way. The experiments and theoretical analysis focus on single- and double-stranded RNA and DNA structures at different hydration levels and with ion atmospheres of controlled composition, structurally characterized by x-ray scattering. As a ground-breaking open problem, the role of magnesium and other ions in RNA structure definition and folding will be addressed by following RNA folding processes with vibrational probes up to milliseconds. The impact of site-bound versus outer ions will be dynamically separated to unravel mechanisms stabilizing secondary and tertiary RNA structures. Beyond RNA research, the present approach holds strong potential for fundamental insight in transmembrane ion channels and channel rhodopsins.

2 330 493 €

Start date: 2019-05-01, End date: 2024-04-30

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