The formation of all carbon-based materials in nature starts with fixation and transformation of carbon dioxide (CO2) into useful chemical compounds. Such reactions are enabled by enzymes which often contain highly active metals as reaction centers that are deeply buried in a protein. In contrast, fine chemical production in industry is nowadays still mainly dependent on fossil fuels as carbon feedstock. Since fossil fuels are a limited resource there is an urgent need for alternative strategies. MOCCA (= Metal Organic Cages for Catalysis Applications) aims for the direct use of CO2 to functionalize olefins and produce higher carbon compounds. Principles from nature will be applied such as incorporation of metal catalysts inside a discrete cavity that allows specific substrate binding and activation. The process is divided into two steps: (1) CO2 reduction and (2) insertion of reaction products into the double bond of olefins, for example by hydroformylation. Both reactions are of high interest in chemical research and industry; several metal complexes have been reported as catalysts. Metal complexes are easily tunable via ligand design and molecular catalysts featuring active site mimics have been prepared. However, the current generation of these systems cannot compete with the efficiency of enzymes. Today it is clear that drastically simplified active site mimics do not fulfill all necessary conditions for keeping up with their natural paradigms, but also the outer shell plays an important role. Thus, the need for wrapping catalytic sites in a tunable chemical environment is evident. The nowadays available toolbox of design-driven supramolecular self-assembly allows the construction of such tailored environments, while investigation of encapsulated catalysts is still in its infancy. MOCCA will demonstrate the first example of molecular coordination cages containing catalysts as linkers that efficiently reduce CO2 and use the reaction products directly for the pro

My objective is to establish methodology expanding the detailed characterization and exploitation of backbone dynamics in complex proteins up to 80-100 kDa monomer molecular weight. Experimental elucidation of protein motion is imperative for fundamental understanding of enzymatic and regulatory features. However, with a limit of regularly around 40-50 kDa maximum total mass, the more complex targets of current scientific interest usually evade solution NMR backbone resonance assignment and remain inaccessible for the majority of sophisticated methods for protein dynamics. This paradigmatic shortcoming has led to serious limitations in the understanding and exploitation of protein dynamics. Here I aim to achieve a two-fold expansion of the accessible molecular-weight range by an unprecedented hybrid strategy. Based on the unmatched prospects of 4D and 5D solid-state NMR (ssNMR) assignment data for a 2x72 kDa protein, I will establish proton-detected, higher-dimensionality ssNMR methodology as a powerful framework for NMR assignment in an unprecedented size range. Subsequently, developing strategies utilizing ssNMR assignments as a springboard to solution NMR will enable detailed characterization of those targets under close-to-physiological conditions. This fundamentally new BYPASS strategy will allow understanding of intramolecular regulatory circuits and coupled motional networks in innumerable, previously inaccessible complex proteins, with a transformative impact for dynamics, in particular allosteric regulation, in structural biology. Fueled by my role as a key player in revolutionizing solid-state NMR via proton-detected, fast magic-angle spinning NMR methodology, my achievements will be paradigmatic for the accessibility and utility of dynamics for the structure-dynamics-function relationship of proteins and will have widespread consequences for a wide range of structural biology and downstream applications such as pharmacology and biotechnology.

The Standard Model of particle physics successfully describes all known particles and their interactions. However, questions like the nature of dark matter or the hierarchy of masses and couplings of quarks and leptons remain to be understood. Hence, one searches for new phenomena that will lead to a superior theory that can explain these questions. All such theories introduce additional quantum corrections. Decay rates of processes which are strongly suppressed in the Standard Model are highly sensitive to these corrections. The LHCb experiment at CERN has recorded the world’s largest sample of beauty mesons. In the five years of this proposal, this sample will be enlarged by more than a factor of five. This sets an optimal environment for precision tests for new phenomena in strongly suppressed beauty decays. This proposal aims to discover new scalar or vector particles in precision measurements of leptonic and semi-leptonic beauty decays. These new particles are not predicted by the Standard Model of particle physics, a potential discovery would mark the most important finding in High Energy Physics of the last decades. Some existing anomalies in flavour data can be interpreted as hints for the particles searched for in this proposal. Two classes of measurements are planned within this proposal: the complete scan of purely leptonic beauty decays which include flavour changing neutral current as well as lepton flavour violating modes. Lepton flavour universality is tested in loop decays through a novel inclusive strategy. All proposed measurements will advance the world’s knowledge significantly and have a large discovery potential.

In mammalian genomes, epigenetic modifications of the nucleobase cytosine occur in both strands of the DNA duplex in the sequence “CpG”, and they are central regulators of gene expression as well as important cancer biomarkers. However, current analytical techniques cannot reveal the combination in that these modifications occur in the two strands of a DNA duplex. The resulting inability to create genomic maps of these “CpG duplex modifcations” represents a major roadblock for future developments in epigenetics research and cancer diagnosis. We have engineered the first affinity enrichment probes for selectively analysing novel CpG duplex modifications, and integrated them into user-friendly and cost-effective kits for genomic mapping. In this project, we will develop and commercialize two kits for mapping of the most important novel CpG duplex modification consisting of 5-methylcytosine and 5-hydroxymethylcytosine for the epigenetics research and the liquid biopsy markets. This will provide decisive new impulses for epigenetics research as well as for cancer biomarker discovery and liquid biopsy, both large and rapidly growing markets.

The study of non-equilibrium dynamics of magnetic degrees of freedom has shown remarkable progress over the past two decades. This is in particular true concerning the understanding of ultrafast magnetization dynamics in classical magnets. In contrast, the field of non-equilibrium spin dynamics of many-body quantum magnetic systems is still in its infancy. Despite a number of ground-breaking recent theoretical proposals, experimental studies in this direction are truly scarce and this research field is a largely unexplored territory. Here I propose to study non-equilibrium dynamics in a number of well-selected quantum spin systems, utilizing a novel and powerful experimental technique – time-resolved terahertz spectroscopy under extreme conditions. By carrying out the here proposed program of non-equilibrium and nonlinear studies on low-dimensional and/or frustrated quantum magnets, I aim to explore and reveal novel physics and the governing fundamental principles for the non-equilibrium quantum spin dynamics. Firstly, I aim to realize novel quantum phenomena and quantum effects, which are difficult to be detected in the equilibrium state, such as complex many-body bound states. Secondly, I will explore novel characteristics for exotic quantum states like quantum spin liquids and quantum critical phases in the nonlinear response regime, by driving the quantum disordered states far from equilibrium. Thirdly, I aim to tune and control the non-equilibrium and nonlinear response of the quantum spin states either by the terahertz electromagnetic fields directly or via coupling to other degrees of freedom, such as phonons. Gaining momentum from the on-going intensive theoretical studies and based on my previous work in the field of quantum spin systems, I anticipate a productive, impactful, and successful research project exploring the new physics offered by non-equilibrium quantum spin systems.