ERC FUNDED PROJECTS

The role of children's behavior and temperament is increasingly acknowledged in family research. Gene-environment Correlation (rGE) processes may account for some child effects, as parents react to children s behavior which is in part genetically influenced (evocative rGE). In addition, passive rGE, in which parenting and children s behavior are correlated through overlapping genetic influences on family members behavior may account in part for the parenting-child behavior relationships. The proposed project will be the first one to directly address these issues with DNA information on family members and quality observational data on parent and child behaviors, following children through early development. Two separate longitudinal studies will investigate the paths from children s genes to their behavior, to the way parents react and modify their parenting towards the child, affecting child development: Study 1 will follow first-time parents from pregnancy through children s early childhood, decoupling parent effect and child effects. Study 2 will follow dizygotic twins and their parents through middle childhood, capitalizing on genetic differences between twins reared by the same parents. We will test the hypothesis that parents' characteristics, such as parenting style and parental attitudes, are associated with children's genetic tendencies. Both parenting and child behaviors will be monitored consecutively, to investigate the co-development of parents and children in an evocative rGE process. Child and parent candidate genes relevant to social behavior, notably those from the dompaminergic and serotonergic systems, will be linked to parents behaviors. Pilot results show children s genes predict parenting, and an important task for the study will be to identify mediators of this effect, such as children s temperament. We will lay the ground for further research into the complexity of gene-environment correlations as children and parents co-develop.

1 443 687 €

Start date: 2010-01-01, End date: 2015-12-31

We plan to investigate the strong coherent interaction of light and matter on the level of individual photons and atoms or atom-like systems. In particular, we will explore large dipole moment superconducting artificial atoms and natural Rydberg atoms interacting with radiation fields contained in quasi-one-dimensional on-chip microwave frequency resonators. In these resonators photons generate field strengths that exceed those in conventional mirror based resonators by orders of magnitude and they can also be stored for long times. This allows us to reach the strong coupling limit of cavity quantum electrodynamics (QED) using superconducting circuits, an approach known as circuit QED. In this project we will explore novel approaches to perform quantum optics experiments in circuits. We will develop techniques to generate and detect non-classical radiation fields using nonlinear resonators and chip-based interferometers. We will also further advance the circuit QED approach to quantum information processing. Our main goal is to develop an interface between circuit and atom based realizations of cavity QED. In particular, we will couple Rydberg atoms to on-chip resonators. To achieve this goal we will first investigate the interaction of ensembles of atoms in a beam with the coherent fields in a transmission line or a resonator. We will perform spectroscopy and we will investigate on-chip dispersive detection schemes for Rydberg atoms. We will also explore the interaction of Rydberg atoms with chip surfaces in dependence on materials, temperature and geometry. Experiments will be performed from 300 K down to millikelvin temperatures. We will realize and characterize on-chip traps for Rydberg atoms. Using trapped atoms we will explore their coherent dynamics. Finally, we aim at investigating the single atom and single photon limit. When realized, this system will be used to explore the first quantum coherent interface between atomic and solid state qubits.

1 954 464 €

Start date: 2009-09-01, End date: 2014-08-31

Cell adhesions play an important role in the organization, growth, maturation, and function of living cells. Interaction of cells with the extracellular matrix (ECM) plays an essential role in a variety of disease states , inflammation, and repair of damaged tissues. At the cellular level, many of the biological responses to external stimuli originate at adhesion loci, such as focal adhesions (FA), which link cells to the ECM . Cell adhesion is mediated by receptor proteins such as cadherins and integrins. The precise molecular composition, dynamics and signalling activity of these adhesion assemblies determine the specificity of adhesion-induced signals and their effects on the cell. However, characterization of the molecular architecture of FAs is highly challenging, and it thus remains unclear how these molecules function together, how they are recruited to the adhesion site, how they are turned over, and how they function in vivo. In this project, I aim to conduct an interdisciplinary study that will provide a quantum step forward in the understanding of the functional organization of FAs. We will analyze, for the first time, the three-dimensional structure of FAs in wild-type cells and in cells deficient in the specific proteins involved in the cell-adhesion machinery. We will study the effect of specific geometries on the functional architecture of focal adhesions in 3D. A combination of state-of-the-art technologies, such cryo-electron tomography of intact cells, gold cluster chemistry for in situ labeling, and modulation of the underlying matrix using micro- and nano-patterned adhesive surfaces, together with correlative light, atomic force and electron microscopy, will provide a hybrid approach for dissecting out the complex process of cell adhesion.In summary, this project addresses the properties of FAs across a wide range of complexities and dimensions, from macroscopic cellular phenomena to the physical nature of these molecular assemblies

1 294 000 €

Start date: 2009-11-01, End date: 2015-10-31

Data mining provides large benefits to the commercial, government and homeland security sectors, but the aggregation and storage of huge amounts of data about citizens inevitably leads to erosion of privacy. To achieve the benefits that data mining has to offer, while at the same time enhancing privacy, we need technological solutions that simultaneously enable data mining while preserving privacy. The current state of the art has focused on providing privacy-preserving solutions for very specific problems, and has thus taken a local perspective. Although this is an important first step in the development of privacy-preserving solutions, it is time for a global perspective on the problem that aims for providing full integrated solutions. Our goal in this research is to study privacy and develop comprehensive solutions for enhancing it in the digital era. Our proposed research project includes foundational research on privacy, an infrastructure level for achieving anonymity over the Internet, key cryptographic tools for constructing privacy-preserving protocols, and development of large-scale applications that are built on top of all of the above. The novelty of our research is in our focus on fundamental issues towards comprehensive solutions that are aimed for large-scale data sources. The project s outcome will allow migration from local solutions for specific problems that are suited for small to medium scale data sources to comprehensive privacy-preserving database and data mining solutions for large scale data warehouses. Achieving this great challenge carries immense scientific, technological and societal rewards.

1 921 316 €

Start date: 2009-10-01, End date: 2014-09-30

At a low temperature, nearly macroscopic quantum states can be sustained in superconducting (SC) Josephson junctions. Recently, these superconducting qubits have been coupled to electromagnetic resonators, in a manner analogous to cavity Quantum Electro Dynamics (QED) which describes the interaction between atoms and quantized oscillation modes in the quantum limit. On the other hand, there is yet no experimental evidence of a mode of a mechanical oscillator, such as that of a miniaturized vibrating string, to be chilled down to its quantum ground state. The main part of the proposal involves the use the coupling of Nanomechanical Resonators (NR) to SC qubits employed as artificial atoms in order to address the quantum-classical interface in mechanical motion. Similarly as the SC qubit can exchange quanta with electrical oscillators, it can, in principle, communicate with mechanical modes. The research will begin with demonstrating this kind of electromechanical interaction. In order to tackle experimental surprises, I plan on launching two parallel paths, one with a charge qubit, the other using a phase qubit. The formidable main goal is to experimentally reach the quantum ground state of a mechanical mode. I will investigate the following routes: Make a 1 GHz frequency NR, corresponding to 50 mK, which will reach the ground state at accessible temperatures. On the other hand, I propose to side-band cool a lower-frequency NR via the attached SC qubit. Near the quantum limit, I will start taking advantage of the NR as a building block of electromechanical quantum information. I also propose to push the QED setup of SC qubits coupled to electrical cavities towards more and more complicated states in order to test quantum mechanics in the nearly classical limit.

1 373 000 €

Start date: 2010-01-01, End date: 2014-12-31

To understand the molecular basis of any biological process, it is critical that one is not only able to visualize and monitor molecular events that underlie this process, but also to possess the tools to manipulate these events in a spatial and temporal fashion both in and out of the cell. The overall objective of this proposal is to apply chemical biology approaches to allow real time monitoring of protein aggregation and to dissect the role of specific disease-associated post-translational modifications, phosphorylation, nitration, and truncation on the structure, aggregation, and biochemical properties of monomeric a-syn in health and disease. To achieve these goals, we plan to use a combination of organic chemistry, molecular biology, proteomics, protein engineering, and semisynthetic strategies to facilitate site-specific introduction of post-translational modifications that can be masked and activated in a controllable manner, both inside and outside living cells. Modified synthetic ±-syn will be introduced into primary neurons and cellular models of synucleinopathies and the consequences of masking or activating specific modifications will be assessed using biochemical, immunofluorescence, and live imaging techniques (Specific Aim 1). The absence of specific molecular probes that allow in vivo monitoring and quantitative measurement of toxic misfolded and aggregation intermediates represents a major impediment to understanding the relationship among protein misfolding, post-translational modification, protein aggregation, neurodegeneration, and cell death in PD and other neurodegenerative disorders. To address this challenge, we plan to develop and characterize novel antibodies that target different species along the amyloid formation pathway of ±-syn (Specific Aim 2).

1 495 400 €

Start date: 2009-12-01, End date: 2014-11-30

The project described in this proposal studies formal proofs and their interaction with computation. The study of propositional proofs is connected to a spectrum of problems in our field, starting with the meta-mathematical quest to explain our failure to understand computation and make progress on the basic questions haunting our field (such as P vs. NP), and ending with the industry-driven quest for better algorithms for solving instances of the satisfiability problem. In a seemingly different direction, the recent introduction of magical probabilistically checkable proofs (PCPs) has opened new horizons in computer science, ranging from a deeper understanding of approximation algorithms and their limits to the construction of super-efficient protocols for the verification of proofs and computations. We suggest to study proofs and computation with three main objectives. First, to construct better SAT solvers via a better understanding of propositional proof systems. Second, to expand the range of applications of PCPs and transform them from the purely theoretical objects that they currently are to practical and accessible formats for use in all settings where proofs are encountered. Third, to expand our theoretical understanding of the intrinsic limits of proofs, with an eye towards explaining why we are unable to make significant progress on central questions in computational complexity. We believe this project can bridge across different regions of computer science such as SAT solving and proof complexity, theory and practice, propositional proofs and probabilistically checkable ones. And its expected impact will start on the theoretical mathematical level that forms the foundation of computer science and percolate to more practical areas of our field.

1 743 676 €

Start date: 2009-12-01, End date: 2015-09-30

Each year 1.1 million new cases of breast cancer will occur among women worldwide and 400,000 women will die from this disease. Although progress has been made in understanding breast tumor biology, most of the relevant molecules and pathways remain undefined. Their delineation is critical to a rational approach to breast cancer therapy. This proposal focuses on the role of the under-explored family of protein-tyrosine phosphatases (PTPs) in the normal and neoplastic breast. Virtually all cell signaling pathways are modulated by reversible protein tyrosine phosphorylation, which is regulated by two classes of enzymes: protein-tyrosine kinases (PTKs) and PTPs. Not surprisingly, tyrosine phosphorylation has an important role in breast development and cancer. Whereas the role of specific PTKs, like the HER2 receptor, in breast cancer is well studied, almost nothing is known about the function of specific PTPs in this disease. Our preliminary data suggest that PTP1B has an important role in breast differentiation and that both PTP1B and SHP2 play positive roles in breast cancer. The two predominant goals of this proposal are: First, to delineate the role of PTP1B and other PTPs in normal breast development and differentiation; second, to address the roles of PTP1B and other PTPs in the maintenance of breast cancer and metastasis and to assess their merits as drug targets. These studies not only use state-of-the-art ex vivo and in vivo models for studying breast pathophysiology, but also cross the boundaries between the developmental and cancer research fields and between basic science and clinical applications. Our research should ultimately lead to the rational design of targeted therapies that will improve the clinical management of patients with breast cancer.

1 571 365 €

Start date: 2010-02-01, End date: 2015-01-31

Probabilistically Checkable Proofs (PCPs) encapsulate the striking idea that verification of proofs becomes nearly trivial if one is willing to use randomness. The PCP theorem, proven in the early 90's, is a cornerstone of modern computational complexity theory. It completely revises our notion of a proof, leading to an amazingly robust behavior: A PCP proof is guaranteed to have an abundance of errors if attempting to prove a falsity. This stands in sharp contrast to our classical notion of a proof whose correctness can collapse due to one wrong step. An important drive in the development of PCP theory is the revolutionary effect it had on the field of approximation. Feige et. al. [JACM, 1996] discovered that the PCP theorem is *equivalent* to the inapproximability of several classical optimization problems. Thus, PCP theory has resulted in a leap in our understanding of approximability and opened the gate to a flood of results. To date, virtually all inapproximability results are based on the PCP theorem, and while there is an impressive body of work on hardness-of-approximation, much work still lies ahead. The central goal of this proposal is to obtain stronger PCPs than currently known, leading towards optimal inapproximability results and novel notions of robustness in computation and in proofs. This study will build upon (i) new directions opened up by my novel proof of the PCP theorem [JACM, 2007]; and on (ii) state-of-the-art PCP machinery involving techniques from algebra, functional and harmonic analysis, probability, combinatorics, and coding theory. The broader impact of this study spans a better understanding of limits for approximation algorithms saving time and resources for algorithm designers; and new understanding of robustness in a variety of mathematical contexts, arising from the many connections between PCPs and stability questions in combinatorics, functional analysis, metric embeddings, probability, and more.

1 639 584 €

Start date: 2009-09-01, End date: 2016-06-30

The fabrication of textiles is one of the oldest cultural technologies. The objective of the proposed interdisciplinary research project is to investigate the historical meanings and functions of the textile medium in art and architecture from the Middle Ages to the present. The exploration of this specific art medium should result in a historical theory or iconology of the textile. The project focussed on the textile discourse engages in a new, complex, and challenging field of research situated between art and architectural history and within cultural and visual studies, involving also other disciplines such as literary studies and social history. Moreover, it aims at connecting the two scientific cultures of the universities and museums, and it draws transdisciplinary expertise from contemporary art. The framework of the project can be described by seven interconnected subject areas which are dedicated to specific questions and which share categories of objects such as figurative tapestries, installation art, literary texts, or architectural materials. This requires a variety of instrumental methods ranging from gender studies to textual analysis, from iconography to anthropological approaches. Two postdoctoral researchers and one doctoral candidate will work on a topic related to one or more of the subject areas. The team s aim is to perform basic research in an innovative and contemporary field, independently of traditional institutional constraints, in order to contribute to the establishment of the history of textile art as an academic discipline and to the advancement of art and architectural history towards a general history of images, media, and artefacts.

686 000 €

Start date: 2009-09-01, End date: 2013-08-31