ERC FUNDED PROJECTS

Crucial processes within cells depend on specific non-covalent interactions which mediate the assembly of proteins and other biomolecules. Deriving structural information to understand the function of these complex systems is the primary goal of Structural Biology. In this application, the recently developed LILBID method (Laser Induced Liquid Bead Ion Desorption) will be optimized for investigation of macromolecular complexes with a mass accuracy two orders of magnitude better than in 1st generation spectrometers. Controlled disassembly of the multiprotein complexes in the mass spectrometric analysis while keeping the 3D structure intact, will allow for the determination of complex stoichiometry and connectivity of the constituting proteins. Methods for such controlled disassembly will be developed in two separate units of the proposed LILBID spectrometer, in a collision chamber and in a laser dissociation chamber, enabling gas phase dissociation of protein complexes and removal of excess water/buffer molecules. As a third unit, a chamber allowing determination of ion mobility (IM) will be integrated to determine collisional cross sections (CCS). From CCS, unique information regarding the spatial arrangement of proteins in complexes or subcomplexes will then be obtainable from LILBID. The proposed design of the new spectrometer will offer fundamentally new possibilities for the investigation of non-covalent RNA, soluble and membrane protein complexes, as well as broadening the applicability of non-covalent MS towards supercomplexes.

1 264 477 €

Start date: 2014-02-01, End date: 2019-01-31

The goal of the research program, ASTROROT, is to significantly advance the knowledge of astrochemistry by exploring its molecular complexity and by discovering new molecule classes and key chemical processes in space. So far, mostly physical reasons were investigated for the observed variations in molecular abundances. We here propose to study the influence of chemistry on the molecular composition of the universe by combining unprecedentedly high-quality laboratory spectroscopy and pioneering telescope observations. Array telescopes provide new observations of rotational molecular emission, leading to an urgent need for microwave spectroscopic data of exotic molecules. We will use newly developed, unique broadband microwave spectrometers with the cold conditions of a molecular jet and the higher temperatures of a waveguide to mimic different interstellar conditions. Their key advantages are accurate transition intensities, tremendously reduced measurement times, and unique mixture compatibility. Our laboratory experiments will motivate and guide astronomic observations, and enable their interpretation. The expected results are • the exploration of molecular complexity by discovering new classes of molecules in space, • the detection of isotopologues that provide information about the stage of chemical evolution, • the generation of abundance maps of highly excited molecules to learn about their environment, • the identification of key intermediates in astrochemical reactions. The results will significantly foster and likely revolutionize our understanding of astrochemistry. The proposed research will go far beyond the state-of-the-art: We will use cutting-edge techniques both in the laboratory and at the telescope to greatly improve and speed the process of identifying molecular fingerprints. These techniques now enable studies at this important frontier of physics and chemistry that previously would have been prohibitively time-consuming or even impossible.

1 499 904 €

Start date: 2015-05-01, End date: 2020-04-30

Biomimetic Organocatalysis – Development of Novel Synthetic Catalytic Methodology and Technology The objective of the proposed research is the design and development of unprecedented preassembled, modular, molecular factories. Inspiration comes from nature’s non-ribosomal peptide synthetases (NRPSs) and polyketide synthetases (PKSs). These large multifunctional enzymes possess catalytic modules with the capacity for recognition, activation and modification required for sequential biosynthesis of complex peptides and polyketides. Using nature as a role model we intend to design and prepare such catalyst “factories” synthetically and apply them in novel cascade reaction sequences. The single catalytic modules employed will be based on organocatalytic procedures, including enamine-, iminium-, as well as hydrogen bonding activation processes, but the potential scope is limitless. Organocatalysts have so far never been applied in a combined fashion utilizing their different activation mechanisms in multiple reaction cascades. Therefore, it is our intention to firstly demonstrate that such a production line approach is feasible and that these new catalyst systems can be applied in the synthesis of valuable enantiopure, biologically active, building blocks and natural products. Additionally, the extensive possibilities to vary organocatalyst modules in sequence will lead to science mimicking nature in its diversity.

999 960 €

Start date: 2008-09-01, End date: 2012-08-31

Combinatorial Computational Chemistry is developed as a standard tool to tackle complex problems in chemistry and materials science. The method employs a series of state-of-the-art methods, ranging from empirical molecular mechanics to first principles calculations, as well as of mathematical (graph theoretical and combinatorial) methods. The process is similar as in experimental combinatorial chemistry: First, a large set of candidate structures is generated which is complete in the sense that the best possible structure for a particular purpose must be found among the set. This structure is then identified using computational chemistry. We will apply methodologies at different stages in hierarchical order and successively screen the set of candidate structures. Screening criteria are based on the computer simulations and include geometry, stability and properties of the candidate structures. Detailed characteristics of the final materials will be simulated, including the X-ray diffraction pattern, the electronic structure, and the target properties. We will apply C3 to two important problems of environmental science. (i) We will optimise nanoporous materials to act as molecular sieves to separate water from ethanol, an important task for the production of biofuels. Here, materials are optimised to transport ethanol, but not water (or vice versa). The tuning parameters are the channel size of the material and its polarity. (ii) We will optimise nanoporous materials to transport protons, an important task for the design of energy-efficient fuel cells, by distributing flexible functional groups, acting as hopping sites for the protons, in the framework.

1 500 000 €

Start date: 2011-02-01, End date: 2016-04-30