ERC FUNDED PROJECTS

An animal’s decision on how to respond to the environment is based not only on the sensory information available, but further depends on internal factors such as stress, sleep / wakefulness, hunger / satiety and experience. Neurotransmitters and neuropeptides in the brain modulate neural circuits accordingly so that appropriate behaviors are generated. Aberrant neuromodulation is implicated in diseases such as insomnia, obesity or anorexia. Given the complexity of most neural systems studied, we lack good models of how neuromodulators systemically affect the activities of neural networks. To overcome this problem, I propose to study neural circuits in the nematode C. elegans, which is a genetically tractable model organism with a simple and anatomically defined nervous system. I will focus on the neural circuits involved in oxygen chemosensory behaviors. Worms can smell oxygen and they use this information to navigate through heterogeneous environments. This enables them to find food and to engage in social interactions. Oxygen chemosensory behaviors are highly modulated by experience and nutritional status, but the underlying mechanisms are not understood. I established behavioral assays that allow studying the modulation of oxygen behaviors in a rigorously quantifiable manner. I also acquired expertise in micro-fabrication technologies and developed imaging devices to measure the activity of neurons in live animals. The first two aims of this proposal focus on the application of these technologies to study (A) how neuropeptides mediate experience dependent modulation of oxygen chemosensory circuits; and (B) how food availability and nutritional status modulate the same neural circuits. Aim (C) is an innovative engineering approach in which I will develop new microfluidic technologies that allow the simultaneous recording of oxygen evoked behaviors and neural activity. This will be beneficial for aims A and B and will pave way for new future research directions.

1 500 000 €

Start date: 2012-01-01, End date: 2017-06-30

The theory of games played on graphs provides the mathematical foundations to study numerous important problems in branches of mathematics, economics, computer science, biology, and other fields. One key application area in computer science is the formal verification of reactive systems. The system is modeled as a graph, in which vertices of the graph represent states of the system, edges represent transitions, and paths represent behavior of the system. The verification of the system in an arbitrary environment is then studied as a problem of game played on the graph, where the players represent the different interacting agents. Traditionally, these games have been studied either with Boolean objectives, or single quantitative objectives. However, for the problem of verification of systems that must behave correctly in resource-constrained environments (such as an embedded system) both Boolean and quantitative objectives are necessary: the Boolean objective for correctness specification and quantitative objective for resource-constraints. Thus we need to generalize the theory of graph games such that the objectives can express combinations of quantitative and Boolean objectives. In this project, we will focus on the following research objectives for the study of graph games with quantitative objectives: (1) develop the mathematical theory and algorithms for the new class of games on graphs obtained by combining quantitative and Boolean objectives; (2) develop practical techniques (such as compositional and abstraction techniques) that allow our algorithmic solutions be implemented efficiently to handle large game graphs; (3) explore new application areas to demonstrate the application of quantitative graph games in diverse disciplines; and (4) develop the theory of games on graphs with infinite state space and with quantitative objectives. since the theory of graph games is foundational in several disciplines, new algorithmic solutions are expected.

1 163 111 €

Start date: 2011-12-01, End date: 2016-11-30

We propose to take the experimental investigation of strongly-correlated quantum matter in the context of ultracold gases to the next scientific level by applying “quantum gas microscopy” to quantum many-body systems with tunable interactions. Tunability, as provided near Feshbach resonances, has recently proven to be a key ingredient for a broad variety of strongly-correlated quantum gas phases with strong repulsive or attractive interactions and for investigating quantum phase transitions beyond the Mott-Hubbard type. Quantum gas microscopy, as recently demonstrated in two pioneering experiments, will be combined with tunability as given by bosonic Cs atoms to give direct access to spatial correlation functions in the strongly interacting regimes of e.g. the Tonks gases, to open up the atom-by-atom investigation of transport properties, and to allow the detection of entanglement. It will provide local control at the quantum level in a many-body system for entropy engineering and defect manipulation. It will allow the generation of random potentials that add to a periodic lattice potential for the study of glass phases and localization phenomena. In a second step, we will add bosonic and fermionic potassium (39-K and 40-K) to the apparatus to greatly enhance the capabilities of the tunable quantum gas microscope, opening up microscopy to fermionic and, in a third step, to fermionic dipolar systems of KCs polar ground-state molecules. In the case of atomic 40-K fermions with tunable contact interactions, the central goal will be to investigate magnetic systems, in particular to create anti-ferromagnetic many-body states. The Cs sample, for which we routinely achieve ultralow temperatures and extremely pure Bose-Einstein condensates, would serve as a perfect coolant and probe. With KCs, which is non-reactive and hence stable, we will enter a qualitatively new regime of fermionic systems with long-range dipolar interactions.

1 477 500 €

Start date: 2012-01-01, End date: 2016-12-31

Non-covalent protein-protein interactions underlie most of biological activity on the molecular level. A binding event between two proteins typically consists of two stages: 1) a diffusional, non-specific search of the binding partners for each other, and 2) specific recognition of the compatible contact surfaces followed by complex-formation. Despite significant progress in studying these processes, a number of open questions remain. How do partners find each other in the crowded and interaction-rich cellular environment? What are the exact mechanisms of the specific recognition of binding surfaces? What is the role of induced fit as opposed to conformational selection in the process? We propose to utilize atomistic-level and coarse-grained molecular dynamics simulations and advanced computational techniques in close collaboration with experiment to address these questions, with the ultimate goal of developing a unified picture combining both specific and non-specific contributions to protein-protein interactions. We will focus on several test-cases of broad biological significance, such as the ubiquitin system, to test two central ideas: 1) that protein dynamics is the principal determinant of specific molecular recognition in many systems, and 2) that co-localization, which non-specifically affects the binding process, is a direct consequence of the general physico-chemical properties of the binding partners, irrespective of the features of their binding sites. Methodologically, we will further develop and utilize distributed computing techniques on the world-wide-web and computation on streaming processors to meet the high demand for computational power, inherent in studying protein interactions in silico. In our work, we will closely collaborate with experimentalists, ranging from NMR and X-ray crystallography experts to molecular biologists to both validate our simulations and theoretical work as well as assist in interpreting experimental findings.

1 495 790 €

Start date: 2011-09-01, End date: 2017-03-31