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.

Proteins, functioning as enzymes, receptors, nanomotors, and transporters, have inspired the creation of numerous artificial molecular systems and materials that mimic biological structures and behaviors. However, replicating their dynamic behaviors and intra-protein communication pathways, which are responsible for allosteric interactions and signal transduction, remains a significant challenge. The "CageComm" project aims to emulate protein-like allosteric interactions and intra-protein communication pathways using multicavity molecular coordination cages. To achieve this, "CageComm" will develop novel directional mechanisms for intra-cage communication, enabling control of one cavity's features through the remote stimulation of another, and integrate them into asymmetric multicavity palladium(II) coordination cages. Like proteins, these coordination cages will be capable of receiving a stimulus, directionally transmitting the signal, and generating outputs such as structural changes, guest binding, or alterations in photophysical and chiroptical properties. Two primary mechanisms for intra-cage communication will be established: guest-induced twisting motion transduction and stimuli-responsive expansion/contraction motion transmission via palladium(II) re-coordination on "gear-like" ligands. Implementing these mechanisms will provide access to advanced features and behaviors of the cages, including structural remote control, remote sensing, cage-to-cage transformations, signal transduction across phase interfaces, and non-linear responsiveness.

Cyber-physical real-time systems are information processing systems that require both functional as well as timing correctness and have interactions with the physical world. Since time naturally progresses in the physical world, safe bounds of deterministic or probabilistic timing properties are required. PropRT will explore the possibilities to construct timing analysis for complex cyber-physical real-time systems from formal properties. The target properties should be modular so that safe and tight analysis as well as optimization can be performed (semi-)automatically. New, mathematical, modulable, and fundamental properties for property-based (schedulability) timing analyses and scheduling optimizations are needed to capture the pivotal properties of cyber-physical real-time systems, and thus enable mathematical and algorithmic research on the topic. Different flexibility and tradeoff options to achieve real-time guarantees should be provided in a modularized manner to enable tradeoffs between execution efficiency and timing predictability. The success of this project will provide a comprehensive view of the landscape of design, analysis, and optimization options for timing properties in cyber-physical real-time systems. Advanced optimization and analytical frameworks based on the formal properties of scheduling algorithms and schedulability analysis will serve as new ingredients for designing predictable cyber-physical systems, which will trigger a revolution of computer architectures, system modeling, communication mechanisms, and synchronization designs in the near future. The results will bring a new design process to further allow control designers and system integrators in cyber-physical real-time systems to jointly explore different configurations of controllers, computation, and communication parameters for designing timing predictable cyber-physical system applications.

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.