ERC FUNDED PROJECTS

We aim to understand host cell entry of enveloped viruses at molecular level. A crucial step in this process is when the viral membrane fuses with the cell membrane. Similarly to cell–cell fusion, this step is mediated by fusion proteins (classes I–III). Several medically important viruses, notably dengue and many bunyaviruses, harbour a class II fusion protein. Class II fusion protein structures have been solved in pre- and post-fusion conformation and in some cases different factors promoting fusion have been determined. However, questions about the most important steps of this key process remain unanswered. I will focus on the entry mechanism of bunyaviruses by using cutting-edge, high spatial and temporal resolution bio-imaging techniques. These viruses have been chosen as a model system to maximise the significance of the project: they form an emerging viral threat to humans and animals, no approved vaccines or antivirals exist for human use and they are less studied than other class II fusion protein systems. Cryo-electron microscopy and tomography will be used to solve high-resolution structures (up to ~3 Å) of viruses, in addition to virus–receptor and virus–membrane complexes. Advanced fluorescence microscopy techniques will be used to probe the dynamics of virus entry and fusion in vivo and in vitro. Deciphering key steps in virus entry is expected to contribute to rational vaccine and drug design. During this project I aim to establish a world-class laboratory in structural and cellular biology of emerging viruses. The project greatly benefits from our unique biosafety level 3 laboratory offering advanced bio-imaging techniques. Furthermore it will also pave way for similar projects on other infectious viruses. Finally the novel computational image processing methods developed in this project will be broadly applicable for the analysis of flexible biological structures, which often pose the most challenging yet interesting questions in structural biology.

1 998 375 €

Start date: 2015-04-01, End date: 2020-03-31

The goal of this project is to explore the fundamental processes which trigger the nucleation and growth of solids. Condensed matter is formed by clustering of atoms, ions or molecules. This initial step is key for the onset of crystallization, condensation and precipitate formation. Yet, despite of the scientific and technological significance of these phenomena, on an atomistic level we merely have expectations on how atoms should behave rather than experimental evidence about how the growth of solid matter is initiated. The classical nucleation theory is commonly in agreement with experiments, provided the original and the final stages are inspected qualitatively. However, the classical theory does not define what fundamentally constitutes a pre-nucleation state or how a nucleus is formed at all. CLUSTER aims at investigating the very early stages of crystalline matter formation on an unprecedented length scale. It shall explore the atomic mechanisms which prompt the formation of solids. Complemented by density functional theory calculations and molecular dynamics simulations, in-situ high-resolution electron microscopy shall be used to investigate the formation, dynamics, stability and evolution of tiniest atomic clusters which represent the embryos of solid matter. Firstly, we investigate the 3D structure of clusters deposited on suspended graphene. Secondly, we focus on cluster formation, the evolution of sub-critical nuclei and the onset of particle growth by thermal activation. Thirdly, using a novel liquid-cell approach in the transmission electron microscope, we control and monitor in-situ cluster formation and precipitation in supersaturated solutions. The results of CLUSTER, which will advance the understanding of the birth of solid matter, are important for the controlled synthesis of (nano-)materials, for cluster science and catalysis and for the development of novel materials.

2 271 250 €

Start date: 2016-06-01, End date: 2021-05-31

It is a fundamental but still elusive question how nociceptive processing is performed in neuronal networks in the cortex for the conscious experience of pain. The objective of this project is to identify and characterize the cortical microcircuits in the anterior cingulate cortex (ACC) that are involved in pain processing with cellular resolution. The ACC is essential for evaluating the emotional/affective component of pain. Our research will investigate the elusive question if a dedicated pain circuit exists in the ACC. We will dissect the detailed structure and connectivity of this pain circuit and investigate how it generates affective behavioural responses related to pain. At the core of this project, we will characterize the neuronal networks in the ACC that are engaged in the processing of noxious stimuli. It will be highly interesting to determine the neuronal dynamics in the ACC during nociception and in chronic pain conditions on the cellular and network level. Furthermore, we will elucidate the downstream targets that are influenced by the pain circuits in the ACC to generate the appropriate behavioural responses. These aims will be achieved by a combination of electrophysiology, 2-photon Ca2+ imaging and pharmaco- and opto-genetic approaches both in vivo and in vitro and behavioural testing of pain affect in mice. This project will give a comprehensive picture of how a cortical microcircuit processes afferent noxious stimuli to generate an affective behavioural response. This study will give important insight into the fundamental question of cortical information processing and it is highly relevant to understand pain processing and the changes in the network dynamics that manifest the transition to chronic pain. Eventually this might contribute to the development of novel treatment strategies for this pathological condition.

1 928 125 €

Start date: 2016-09-01, End date: 2021-08-31

The oxygen evolution reaction (OER) is the key reaction to enable the storage of solar energy in the form of hydrogen fuel through water splitting. Efficient, Earth-abundant, and robust OER catalysts are required for a large-scale and cost-effective production of solar hydrogen. While OER catalysts based on metal oxides exhibit promising activity and stability, their rational design and developments are challenging due to the heterogeneous nature of the catalysts. Here I propose a project to (i) understand OER on metal oxides at the molecular level and engineer catalytic sites at the atomic scale; (ii) develop and apply practical OER catalysts for high-efficiency water splitting in electrochemical and photoelectrochemical devices. The first general objective will be obtained by using 2-dimensional metal oxide nanosheets as a platform to probe the intrinsic activity and active sites of metal oxide OER catalysts, as well as by developing sub-nanocluster and single-atom metal oxide OER catalysis. The second general objective will be obtained by establishing new and better synthetic methods, developing new classes of catalysts, and applying catalysts in innovative water splitting devices. The project employs methodologies from many different disciplines in chemistry and materials science. Synthesis is the starting point and the backbone of the project, and the synthetic efforts are complemented and valorised by state-of-the-art characterization and catalytic tests. The project will not only yield significant fundamental insights and knowledge in heterogeneous OER catalysis, but also produce functional and economically viable catalysts for solar fuel production.

2 199 983 €

Start date: 2016-07-01, End date: 2021-06-30