ERC FUNDED PROJECTS

This proposal brings together two fields in biology, namely the emerging field of phase-separated assemblies in cell biology and state-of-the-art cellular cryo-electron tomography, to advance our understanding on a fundamental, yet illusive, question: the molecular organization of the cytoplasm. Eukaryotes organize their biochemical reactions into functionally distinct compartments. Intriguingly, many, if not most, cellular compartments are not membrane enclosed. Rather, they assemble dynamically by phase separation, typically triggered upon a specific event. Despite significant progress on reconstituting such liquid-like assemblies in vitro, we lack information as to whether these compartments in vivo are indeed amorphous liquids, or whether they exhibit structural features such as gels or fibers. My recent work on sample preparation of cells for cryo-electron tomography, including cryo-focused ion beam thinning, guided by 3D correlative fluorescence microscopy, shows that we can now prepare site-specific ‘electron-transparent windows’ in suitable eukaryotic systems, which allow direct examination of structural features of cellular compartments in their cellular context. Here, we will use these techniques to elucidate the structural principles and cytoplasmic environment driving the dynamic assembly of two phase-separated compartments: Stress granules, which are RNA bodies that form rapidly in the cytoplasm upon cellular stress, and centrosomes, which are sites of microtubule nucleation. We will combine these studies with a quantitative description of the crowded nature of cytoplasm and of its local variations, to provide a direct readout of the impact of excluded volume on molecular assembly in living cells. Taken together, these studies will provide fundamental insights into the structural basis by which cells form biochemical compartments.

1 228 125 €

Start date: 2018-02-01, End date: 2023-01-31

Pharaonic Egypt is commonly known for its pyramids and tomb treasures. The present knowledge of Egyptian everyday life and social structures derives mostly from mortuary records associated with the upper classes, whereas traces of ordinary life from domestic sites are generally disregarded. Settlement archaeology in Egypt and Nubia (Ancient North Sudan) is still in its infancy; it is timely to strenghten this field. Responsible for the pottery at three major settlement sites (Abydos and Elephantine in Egypt; Sai Island in Sudan), the PI is in a unique position to co-ordinate a research project on settlement patterns in Northeast Africa of the 2nd millennium BC based on the detailed analysis of material remains. The selected case studies situated across ancient and modern borders and of diverse environmental and cultural preconditions, show very similar archaeological remains. Up to now, no attempt has been made to explain this situation in detail. The focus of the project is the well-preserved, only partially explored site of Sai Island, seemingly an Egyptian microcosm in New Kingdom Upper Nubia. Little time is left to conduct the requisite large-scale archaeology as Sai is endangered by the planned high dam of Dal. With the application of microarchaeology we will introduce an approach that is new in Egyptian settlement archaeology. Our interdisciplinary research will result in novel insights into (a) multifaceted lives on Sai at a micro-spatial level and (b) domestic life in 2nd millennium BC Egypt and Nubia from a macroscopic view. The present understanding of the political situation in Upper Nubia during the New Kingdom as based on written records will be significantly enlarged by the envisaged approach. Furthermore, in reconstructing Sai Island as “home away from home”, the project presents a showcase study of what we can learn about acculturation and adaptation from ancient cultures, in this case from the coexistence of Egyptians and Nubians

1 497 460 €

Start date: 2012-12-01, End date: 2018-04-30

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

Primary energy conversion in nature is powered by highly efficient enzymes that capture chemical or light energy and transduce it into other energy forms. These processes are catalyzed by coupled transfers of protons and electrons (PCET), but their fundamental mechanistic principles are not well understood. In order to obtain a molecular-level understanding of the functional elements powering biological energy conversion processes, we will study the catalytic machinery of one of the largest and most intricate enzymes in mitochondria and bacteria, the respiratory complex I. This gigantic redox-driven proton-pump functions as the entry point for electrons into aerobic respiratory chains, and it employs the energy released from a chemical reduction process to transport protons up to 200 Å away from its active site. Its molecular structure from bacteria and eukaryotes was recently resolved, but the origin of this remarkable action-at-a-distance effect still remains unclear. We employ and develop multi-scale quantum and classical molecular simulation techniques in combination with de novo-protein design methodology to identify and isolate the functional elements that catalyze the long-range PCET reactions in complex I. To fully understand the natural PCET-elements, we will further engineer central parts of this machinery into artificial protein frameworks, with the goal of designing modules for redox-driven proton pumps from first principles. The project aims to establish a fundamental understanding of nature's toolbox of catalytic elements, to elucidate how the complex biochemical environment contributes to the catalytic effects, and to provide blueprints that can guide the design of man-made enzymes for sustainable energy technology.

1 494 368 €

Start date: 2017-02-01, End date: 2022-01-31