ERC FUNDED PROJECTS

This proposal intends to develop and apply a new-generation theoretical toolbox for understanding the rich dynamics of strongly-interacting many-body quantum sytems subjected to destabilizing manipulations bringing them very far from equilibrium. In atomic systems, condensed matter and nanophysics settings, quantum matter is nowadays routinely pushed beyond the traditional low-energy/linear response/thermal equilibrium paradigms. Some experiments even clearly highlight the need to revise basic fundamental quantum statistical mechanics notions such as ergodicity, relaxation and thermalization in order to explain their behaviour. Theory must thus urgently revise its textbooks and develop new interpretations and capabilities for offering concrete, quantitative phenomenology. This proposal is focused on a set of systems at the very center of this strongly-correlated, experimentally realizable far-from-equilibrium spectacle: integrable models of quantum spin chains, interacting gases confined to one spatial dimension, and quantum dots. Building up on recent theoretical breakthroughs in dynamical correlations and post-quench steady states, this proposal aims to shed a new light on the fundamental principles at the heart of many-body quantum dynamics. It will implement a broad and ambitious research agenda consisting of synergetic projects from mathematically formal thought experiments all the way to phenomenologically applied practical calculations. The types of protocols to be studied include probes creating high-energy excitations, pulses inducing changes beyond linear response, quenches causing sudden global reorganizations, all the way to drivings completely metamorphozing the physical states. The result will be to provide reliable, experimentally relevant and urgently-needed theoretical `anchoring points' in our general understanding of the physics underlying far-from-equilibrium strongly-interacting quantum matter.

2 444 446 €

Start date: 2017-09-01, End date: 2022-08-31

Holography is by now a fundamental tool in the understanding of both strongly coupled conformal field theories (CFTs) and quantum theories of gravity. While holography in Anti de Sitter (AdS) space-times is rather well understood, we currently lack a basic picture of what it means in non-AdS space-times. Considering non-AdS space-times is an essential and urgent next step in the study of quantum gravity as we seem to live in a universe with a positive cosmological constant that is approaching de Sitter (dS) in the far future. Also, the near-horizon geometries of black holes are typically described by more exotic geometries that need to be understood on their own right. I propose to address this and study the physics of holographic systems on non-AdS space-times and their connection to generalized geometric structures that naturally arise in these setups. In order do this I will use both conventional field theory techniques and new holographic tools, some of which I have developed recently. The relevance of GenGeoHol is illustrated by universal properties of black holes, e.g. their area-law entropy. These are independent of AdS, pointing towards the existence of a more general holographic principle that generalizes the usual symmetries and geometric notions. A great deal of evidence has accumulated recently indicating that this is indeed the case. The physics of extremal black holes and non relativistic systems are clear examples. GenGeoHol will impact a wide range of fields. As one moves away from AdS Einstein gravity, the dual quantum-field theories present different symmetries from that of usual relativistic systems. These systems couple naturally to generalized background geometries which are of intrinsic interest and key to a range of concepts extending from Newton-Cartan geometry in non-relativistic systems to higher-spin geometries for so-called W_N CFTs. Given my experience and track record, I am uniquely positioned to attack this problem successfully.

1 300 775 €

Start date: 2017-09-01, End date: 2022-08-31

“Equipped with his five senses, man explores the universe around him and calls the adventure science” E.P. Hubble It is amazing how much we have learned about the working of our universe by using our five senses and how little we still know about the working of these senses themselves! Even though the molecular mechanism of sight, taste, and smell is known, we still don’t know how the mechanical sensations of touch and hearing function at the molecular level. Mechanosensitive (MS) ion channels, present in membranes, are the molecules that sense membrane tension in all species ranging from bacteria to man. They stay functional even in artificial membranes, indicating that mechanosensation occurs at the protein-lipid interface. In an effort to understand the mechanism of force sensation, the major limitation has been the inability to ‘observe’ the molecular changes occurring in MS channels from the onset of the force. The aim of this proposal is to understand how channel proteins sense mechanical force at the molecular level. A bacterial channel, MscL, will be used as a model for its natural function to couple tension in the membrane to protein conformational changes. Here, on the basis of my recent findings, I propose to build on synthetic biology approaches to develop unique tools to specifically address the MS channel, allowing controlling its activity extrinsically and reversibly. In combination with the spectroscopic techniques, I want to elucidate the mechanism of mechanosensation in MscL by measuring structural changes in the protein and its interaction with the surrounding lipids, starting from the onset of the force. The research will clarify not only the long-standing question of how MscL senses tension, but it will also shed light on the common property of mechanosensitivity among nature’s sensors in higher organisms; transient receptor-potential (TRP) channels, which are involved in hearing, touching and other sensory actions.

1 449 236 €

Start date: 2008-09-01, End date: 2014-02-28

Optical switches are photoisomerizable compounds that allow to remotely controlling the activity of proteins, cells and entire organisms with light. These tools are revolutionizing research in biology with their high selectivity and spatiotemporal resolution. Here we propose to develop and apply optical switches to investigate the fundamental processes of secretion, exocytosis and endocytosis, in a way that is non-invasive, acute, and orthogonal to pharmacological and electrophysiological techniques. The optical control of exocytosis will be carried out by means of photoswitchable, Ca2+-permeable channels (LiGluR and Channelrhodopsin-2) which allow triggering vesicle fusion at single synaptic terminals. This procedure will allow studying vesicle release kinetics and the differences between synapses of the same neuron. The photocontrol of endocytosis will be carried out with: (1) inhibitory peptides of the clathrin pathway modified with an azobenzene crosslinker in order to photomodulate their structure and affinity, and (2) photoswitchable synthetic compounds based on chemical inhibitors of dynamin. Photomodulation of endocytosis in chromaffin cells and neurons will allow interfering with the internalisation of membrane receptors with an unprecedented spatial and temporal control. The use of photoswitchable inhibitors of endocytosis would allow for the first time to manipulate reversibly and with subcellular resolution, the vesicular trafficking of the endocytic pathway. In addition, these photoswitches could reveal how endocytosis regulates spatially receptor activation, controlling cell patterning and cell fate.

1 338 000 €

Start date: 2008-09-01, End date: 2013-08-31

Quantum communication networks consist of several nodes that are connected by quantum channels. By exchanging quantum particles, the nodes share quantum correlations, also know as entanglement. Essential for the future development of quantum communication is to understand the design of efficient protocols for the distribution of entanglement between arbitrarily distant nodes. The main objective of the present proposal is to construct the theory of entanglement distribution through quantum networks. At present, very little is known about this fundamental problem, namely about which properties of a quantum network are required to be able to establish entanglement over large distances. Very recently, we have proved that the distribution of entanglement through quantum networks defines a new type of critical phenomenon, an entanglement phase transition called entanglement percolation. These surprising effects do not appear in the standard repeater configuration previously considered. Crucial for the construction of these examples is the use of concepts already known in statistical mechanics, such as percolation. Our scope is to go far beyond these proof-of principle examples and derive the general theoretical framework describing entanglement percolation, exploiting the connection between statistical concepts and entanglement theory. The obtained framework will also be applied to other information resources, such as secret bits. Then, the ultimate aim of the project is to provide a global picture of the distribution of quantum information resources over realistic quantum communication networks.

699 600 €

Start date: 2008-11-01, End date: 2013-12-31

I propose to explore the properties of a novel state of matter, the Quark-Gluon Plasma (QGP), created by colliding atomic nuclei at the highest energy ever reached using triggered particle correlations. The QGP is predicted by the fundamental theory of strong interactions and is characterized by an equilibrated system of free quarks and gluons that are the constituents of atomic nuclei. My investigation of the QGP properties will give unique insights into the development of the early universe and the properties of matter under extreme conditions. Among other results, particle correlation measurements have revealed first compelling evidence for the existence of the QGP state. Due to the limited sensitivity of the used probes, the conclusions are to some extent qualitative rather than quantitative. To get a deeper understanding of the mechanisms at work I propose to study heavy-quark correlations and their in-medium modification in collisions of heavy nuclei by combining the information from different detection systems. I have verified the feasibility of this measurement at lower energies. I am currently one of the world’s experts in measuring heavy-quark correlations and I propose to perform such a measurement at the forefront particle accelerator, the Large Hadron Collider, located at the European Laboratory for Particle Physics CERN. My investigation will be done utilizing the dedicated ALICE (A Large Ion Collider Experiment) detector, which is most suited for measurements in heavy-ion collisions. I would like to do my project with one Postdoc and one Ph.D. student during a period of five years. My research team will be embedded in one of the leading institutes in the field of heavy-ion physics which provided a crucial hardware component to the ALICE experiment. My expertise and the outstanding working environment will guarantee high quality in performing my key measurement. The ALICE experiment will be the place of new discoveries.

850 000 €

Start date: 2008-09-01, End date: 2013-08-31

Rheumatoid Arthritis (RA) causes long lasting disability. At the time of clinically evident arthritis and diagnosis, the disease is already persisting, requiring long-term suppressive treatment. My overarching aim is to prevent chronic arthritis and RA by inhibiting the evolving auto-immune response in a pre-arthritis phase. Currently, identification of RA-patients before the classic presentation with clinically evident chronic arthritis is beyond the state of the art. I here aim to achieve this early recognition by increasing the mechanistic understanding of pre-arthritis phases. I intend to study RA-specific auto-immune responses at the cellular and humoral level as well as markers reflecting local and systemic inflammation. These aspects are selected based on my world-wide validated rule to predict RA-development in early arthritis and on recent work on progression from Clinically Suspect Arthralgia (CSA) to clinical arthritis. This project is now finally feasible, thanks to unique ‘pre-RA’ cohorts and cross-boundary preparatory work done with basic scientists, clinicians and engineers. My research concept is to integrate the products of separate trajectories in a longitudinal study and translate it to the clinic. Patients with CSA will be studied serially in time. Using validated methods and novel techniques and insights we will: delineate molecular and predictive features of RA-specific auto-antibodies and auto-antibody secreting B-cells, identify improved markers of systemic inflammation and test and validate a computer-aided image analysis system to detect subclinical joint inflammation on MRI. Serial data will be combined to reveal interactions between markers and time relationships. Lastly a prediction model identifying imminent RA will be developed. The forefront position of my group allows national and international validation. Together, this multidisciplinary and intersectorial project will open new horizons for preventive, targeted interventions.

1 500 000 €

Start date: 2017-10-01, End date: 2022-09-30

The overarching objective of STOP-HF is to generate human induced pluripotent stem cells (hiPSC) derived cardiomyocytes from two specific forms of heart failure (HF) with a clear trigger to unravel common pathophysiological mechanisms involved in the early development of HF. The project is focused on two specific forms of HF, both with a clear trigger: pregnancy and anthracyclines. Better understanding of early molecular pathways leading to HF and knowledge about inter-individual susceptibility is needed. For detection of early changes on a molecular level cardiac tissue is needed. Generation of patient specific cardiac cells from skin fibroblasts (hiPSC technology) is a novel and innovative approach. SPECIFIC OBJECTIVES 1. Fabrication and maturation of 3D cardiac tissue from hiPS derived cardiomyocytes. 2. Generate and characterize hiPS derived cardiomyocytes and endothelial cells from females with pregnancy induced HF and unravel differences on transcriptome level. 3. Generate and characterize hiPSC derived cardiomyocytes from patients with high susceptibility and resilience to develop anthracycline-induced HF and compare them on transcriptome level. 4. Integrate the results for coding and non-coding RNAs from objective 1+2 and identify overlapping pathways. 5. Validate discoveries on transcriptome level in vitro, in vivo and apply for the development of HF in the general population. WORKPACKAGES WP1: Optimize fabrication and maturation of 3D cardiac tissue from hiPS derived cardiomyocytes WP 2A:Validate the model and compare hiPS derived cardiomyocytes and endothelial cells from PPCM and healthy sisters on transcriptome level; WP 2B:Validate the model and compare hiPS derived cardiomyocytes from both patients with high susceptibility and resilience to develop HF after anthracyclins on transcriptome level; WP 3:Integration of transcriptome data from WP 2A+2B; WP 4:Validation of novel pathways in vitro, in vivo and new onset HF in the general population.

1 496 875 €

Start date: 2017-03-01, End date: 2022-02-28

In nature, molecular hydrogen is produced by the hydrogenase and the nitrogenase enzymes. Nitrogenase reduces dinitrogen to ammonia and, in this process, it evolves hydrogen. Nitrogenase and hydrogenase are oxygen-sensitive enzymes. We chose to optimize a hydrogen production system based on nitrogenase for four reasons: some organisms carrying nitrogenase simultaneously perform photosynthesis and hydrogen evolution by nitrogenase (direct biophotolysis), thus harvesting solar energy and autonomously converting it into chemical energy in a continuous process; cellular mechanisms exist to protect nitrogenase from oxygen but do not appear to exist for hydrogenase; because nitrogenase couples ATP hydrolysis to hydrogen evolution, this enzyme is able to generate hydrogen against a substantial gas pressure; finally, the biochemistry of the nitrogenase system is well known. The objective of our proposal is to provide new eco-efficient strategies for the biological production of hydrogen. Energy research is a priority theme under the Seventh Research Framework (FP7) cooperation program. The objective of energy research under FP7 is to adapt the current energy system into a more sustainable, competitive and secure one, with emphasis and support given to hydrogen research and renewable fuel production. Our proposal has three major components: (i) in vitro evolution of nitrogenase, in which we generate new nitrogenase variants by metagenomic gene shuffling and random mutagenesis, and select those with increased hydrogen production activity; (ii) the development of a genetic system to select for hydrogen overproducers; and (iii) a biochemical element designed to understand the biochemical requisites for efficient hydrogen production by the molybdenum nitrogenase as a basis for its re-engineering.

1 968 000 €

Start date: 2008-10-01, End date: 2014-09-30