ERC FUNDED PROJECTS

For over a century it was believed that ammonium could only be oxidized by microbes in the presence of oxygen. The possibility of anaerobic ammonium oxidation (anammox) was considered impossible. However, about 10 years ago the microbes responsible for the anammox reaction were discovered in a wastewater plant. This was followed by the identification of the responsible bacteria. Recently, the widespread environmental occurrence of the anammox bacteria was demonstrated leading to the realization that anammox bacteria may play a major role in biological nitrogen cycling. The anammox bacteria are unique microbes with many unusual properties. These include the biological turn-over of hydrazine, a well known rocket fuel, the biological synthesis of ladderane lipids, and the presence of a prokaryotic organelle in the cytoplasma of anammox bacteria. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the anammox bacteria. Such understanding contributes directly to our environment and economy because the anammox bacteria form a new opportunity for nitrogen removal from wastewater, cheaper, with lower carbon dioxide emissions than existing technology. Scientifically the results will contribute to the understanding how hydrazine and dinitrogen gas are made by the anammox bacteria. The research will show which gene products are responsible for the anammox reaction, and how their expression is regulated. Furthermore, the experiments proposed will show if the prokaryotic organelle in anammox bacteria is involved in energy generation. Together the environmental and metabolic data will help to understand why anammox bacteria are so successful in the biogeochemical nitrogen cycle and thus shape our planets atmosphere. The different research lines will employ state of the art microbial and molecular methods to unravel the exceptional properties of these highly unusual and important anammox bacteria.

2 500 000 €

Start date: 2009-01-01, End date: 2013-12-31

Bacteria in nature exhibit remarkable capacity to sense their surroundings and rapidly adapt to diverse conditions by gaining new beneficial traits. This extraordinary feature facilitates their survival when facing extreme environments. Utilizing Bacillus subtilis as our primary model organism, we propose to study two facets of this vital bacterial attribute: communication via extracellular nanotubes, and persistence as resilient spores while maintaining the potential to revive. Exploring these fascinating aspects of bacterial physiology is likely to change our view as to how bacteria sense, respond, endure and communicate with their extracellular environment. We have recently discovered a previously uncharacterized mode of bacterial communication, mediated by tubular extensions (nanotubes) that bridge neighboring cells, providing a route for exchange of intracellular molecules. Nanotube-mediated molecular sharing may represent a key form of bacterial communication in nature, allowing for the emergence of new phenotypes and increasing survival in fluctuating environments. Here we propose to develop strategies for observing nanotube formation and molecular exchange in living bacterial cells, and to characterize the molecular composition of nanotubes. We will explore the premise that nanotubes serve as a strategy to expand the cell surface, and will determine whether nanotubes provide a conduit for phage infection and spreading. Furthermore, the formation and functionality of interspecies nanotubes will be explored. An additional mode employed by bacteria to achieve extreme robustness is the ability to reside as long lasting spores. Previously held views considered the spore to be dormant and metabolically inert. However, we have recently shown that at least one week following spore formation, during an adaptive period, the spore senses and responds to environmental cues and undergoes corresponding molecular changes, influencing subsequent emergence from quiescence.

1 497 800 €

Start date: 2014-04-01, End date: 2019-03-31

"The goal of this project is to achieve breakthroughs in a few fundamental questions in 2D statistical physics, using techniques from complex analysis, probability, dynamical systems, geometric measure theory and theoretical physics. Over the last decade, we significantly expanded our understanding of 2D lattice models of statistical physics, their conformally invariant scaling limits and related random geometries. However, there seem to be serious obstacles, preventing further development and requiring novel ideas. We plan to attack those, in particular we intend to: (A) Describe new scaling limits by Schramm’s SLE curves and their generalizations, (B) Study discrete complex structures and use them to describe more 2D models, (C) Describe the scaling limits of random planar graphs by the Liouville Quantum Gravity, (D) Understand universality and lay framework for the Renormalization Group Formalism, (E) Go beyond the current setup of spin models and SLEs. These problems are known to be very difficult, but fundamental questions, which have the potential to lead to significant breakthroughs in our understanding of phase transitions, allowing for further progresses. In resolving them, we plan to exploit interactions of different subjects, and recent advances are encouraging."

1 995 900 €

Start date: 2014-01-01, End date: 2018-12-31

In the last decade, the fields of nanoplasmonics and photonic crystals have opened up the nanoscale for optical control. Both the flow and emission of light can be controlled at these small length scales, giving rise to new science and applications. Interestingly, freely propagating light beams can already contain nanoscale features, i.e. optical singularities. Little is known about this nanoscale structure of light. I propose to (1) reveal the structure of light at the nanoscale and its interaction with geometrical structures or other light structures; and (2) achieve full spatio-temporal control of the nanoscale structure of light. Crucial to achieving these goals are technological innovations, which will be crosscutting objectives. These include the first nonlinear vectorial scanning near-field microscope and novel near-field probes allowing access to new combinations of vector fields. This next step in the field of nano-optics is possible due to recent breakthroughs in the control and visualization of light at the nanoscale obtained in my group. I will combine newly acquired access to the vectorial nature of light with its active control to investigate how (deep-) subwavelength structures of light of different frequencies affect each other when coupled through a nonlinear interaction in a nanostructured material. In parallel I will focus on optical singularities. Because of their extreme size, small changes in their position will lead to huge effects in the local light fields, opening up potential for all-optical and therefore ultrafast control. The research will lead to innovations in the visualization and control of light at the nanoscale, access to the magnetic component of light, nanoscale nonlinear optics and coherent control of light fields. The knowledge gain will be crucial for applications like ultrasensitive biosensors based on superchiral light, ultrafast magneto-optics and nanoscale quantum optics.

2 493 600 €

Start date: 2014-03-01, End date: 2019-02-28

Discrete Mathematics is a fundamental mathematical discipline as well as an essential component of many mathematical areas, and its study has experienced an impressive growth in recent years. Some of the main reasons for this growth are the broad applications of tools and techniques from extremal and probabilistic combinatorics in the rapid development of theoretical Computer Science, in the spectacular recent results in Additive Number Theory and in the study of basic questions in Information Theory. While in the past many of the basic combinatorial results were obtained mainly by ingenuity and detailed reasoning, the modern theory has grown out of this early stage, and often relies on deep, well developed tools, like the probabilistic method, algebraic, topological and geometric techniques. The work of the principal investigator, partly jointly with several collaborators and students, and partly in individual efforts, has played a significant role in the introduction of powerful algebraic, probabilistic, spectral and geometric techniques that influenced the development of modern combinatorics. In the present project he aims to try and further develop such tools, trying to tackle some basic open problems in Combinatorics, as well as significant questions in Additive Combinatorics, Information Theory, and theoretical Computer Science. Progress on the problems mentioned in this proposal, and the study of related ones, is expected to provide new insights on these problems and to lead to the development of novel fruitful techniques that are likely to be useful in Discrete Mathematics as well as in related areas.

1 061 300 €

Start date: 2008-12-01, End date: 2013-11-30

The world is seasonal and organisms’ adjustment of their seasonal timing to this environmental variation is crucial for their fitness. Climate change is strongly impacting seasonal timing which makes a better understanding of the potential for micro-evolution of timing in natural populations essential. As any phenotypic change ultimately involves changes in the physiological mechanism underlying timing, we need to unravel the genetics of these mechanisms. I will carry out a highly integrated eco-evo-devo project on the causes and consequences of genetic variation in timing of reproduction in great tits (Parus major), an ecological model species for that we recently developed state-of-the-art genomic tools. I will develop a powerful instrument to study this timing mechanism by creating selection lines of early and late reproducing birds using genome-wide, rather than phenotypic, selection. The phenotypic response of selection lines birds will be assessed both in controlled environment aviaries and in birds introduced to the wild. To unravel how selection has altered the birds’ physiology I will measure key components of the physiological mechanism at the central, peripheral and egg production levels. As a unique next step I will then introduce selection line birds into a wild population to assess the fitness of these extreme phenotypes. This will enable me, for the first time, to estimate the selection on timing without confounds, which I will compare with traditional estimates using observational data. Finally, I will integrate genetics, physiology and ecology to hindcast the rate of genetic change in our wild population and validate this rate using DNA sampled over a 20-year period. This innovative project integrates state of the art developments in ecology, genetics and physiology (eco-evo-devo) will set new standards for future studies in other wild species and will be of key importance for our predictions of evolutionary responses to a warming world.

2 495 808 €

Start date: 2014-01-01, End date: 2018-12-31

For over a century it was believed that methane (CH4) could only be oxidized by micro-organisms in the presence of oxygen. The possibility of nitrate-dependent or metal-dependent anaerobic oxidation of CH4 (AOM) was generally dismissed. However, about 6 years ago the microbes responsible for the nitrate-AOM reaction were discovered. This was followed by molecular approaches that resulted in the identification of the responsible Methylomirabilis oxyfera bacteria. Recently, the widespread environmental occurrence of these bacteria was demonstrated leading to the realization that AOM may play a significant role in the CH4 and nitrogen cycles. M. oxyfera is a unique microbe with unusual properties that we only begin to understand: the production of oxygen from NO by a putative NO dismutase and a very unusual polygonal cell shape. Even less is known about metals (Fe3+ or Mn4+) as electron acceptors for AOM. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the M. oxyfera bacteria, and to enrich new metal-dependent AOM microbes. Such understanding contributes directly to our environment and economy because AOM is a new sustainable opportunity for nitrogen removal from wastewater. The results will show how the CH4, nitrogen and iron cycles are connected and may lead to new ways of mitigating methane emission. The biodiversity and contribution of AOM-microbes to the biogeochemical cycles in oxygen-limited ecosystems will be investigated, and new metal-AOM enrichments will be performed. Together the environmental and metabolic data will help to understand how and to what extent AOM-microbes contribute to the biogeochemical cycles and thus shape atmosphere of our planet. The research lines will employ state-of-the- art methods to unravel the exceptional properties of these highly unusual and important microbes. The experiments will be performed in one of the world best equipped laboratories for microbial ecology.

2 500 000 €

Start date: 2014-01-01, End date: 2018-12-31

The purpose of this proposal is to investigate from various perspectives some equidistribution problems associated with homogeneous spaces of arithmetic type: a typical problem (basically solved) is the distribution of the set of representations of a large integer by an integral quadratic form. Another harder problem is the study of the distribution of special points on Shimura varieties. In a different direction (linked with quantum chaos), the study of the concentration of Laplacian (Maass) eigenforms or of sections of holomorphic bundles is related to similar problems. Given X such a space and G>L the underlying algebraic group and its corresponding lattice L, the above questions boil down to studying the distribution of H-orbits x.H (or more generally H-invariant measures)on the quotient L\G for some subgroups H. This question may be studied different methods: Harmonic Analysis (HA): given a function f on L\G one studies the period integral of f along x.H. This may be done by automorphic methods. In favorable circumstances, the above periods are related to L-functions which one may hope to treat by methods from analytic number theory (the subconvexity problem). Ergodic Theory (ET): one studies the properties of weak*-limits of the measures supported by x.H using rigidity techniques: depending on the nature of H, one might use either rigidity of unipotent actions or the more recent rigidity results for torus actions in rank >1. In fact, HA and ET are intertwined and complementary : the use of ET in this context require a substantial input from number theory and HA, while ET lead to a soft understanding of several features of HA. In addition, the Langlands correspondence principle make it possible to pass from one group G to another. Based on earlier experience, our goal is to develop these interactions systematically and to develop new approaches to outstanding arithmetic problems :eg. the subconvexity problem or the Andre/Oort conjecture.

866 000 €

Start date: 2008-12-01, End date: 2013-11-30

Expander graphs are finite graphs which play a fundamental role in many areas of computer science such as: communication networks, algorithms and more. Several areas of deep mathematics have been used in order to give explicit constructions of such graphs e.g. Kazhdan property (T) from representation theory of semisimple Lie groups, Ramanujan conjecture from the theory of automorphic forms and more. In recent years, computer science has started to pay its debt to mathematics: expander graphs are playing an increasing role in several areas of pure mathematics. The goal of the current research plan is to deepen these connections in both directions with special emphasis of the more recent and surprising application of expanders to group theory, the geometry of 3-manifolds and number theory.

1 082 504 €

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

The ubiquitous FIC domain catalyzes post-translational modifications (PTMs) of target proteins; i.e. adenylylation (=AMPylation) and, more rarely, uridylylation and phosphocholination. Fic proteins are thought to play critical roles in intrinsic signaling processes of prokaryotes and eukaryotes; however, a subset encoded by bacterial pathogens is translocated via dedicated secretion systems into the cytoplasm of mammalian host cells. Some of these host-targeted Fic proteins modify small GTPases leading to collapse of the actin cytoskeleton and other drastic cellular changes. Recently, we described a large set of functionally diverse homologues in pathogens of the genus Bartonella that are required for their “stealth attack” strategy and persistent course of infection [1, 2]. Our preliminary functional analysis of some of these host-targeted Fic proteins of Bartonella demonstrated adenylylation activity towards novel host targets (e.g. tubulin and vimentin). Moreover, in addition to the canonical adenylylation activity they may also display a competing kinase activity resulting from altered ATP binding to the FIC active site. Finally, we described a conserved mechanism of FIC active site auto- inhibition that is relieved by a single amino acid exchange [1], thus facilitating functional analysis of any Fic protein of interest. Despite this recent progress only a few Fic proteins have been functionally characterized to date; our understanding of the functional plasticity of the FIC domain in mediating diverse target PTMs and their specific roles in infection thus remains limited. In this project, we aim to study the vast repertoire of host-targeted Fic proteins of Bartonella to: 1) identify novel target proteins and types of PTMs; 2) study their physiological consequences and molecular mechanisms of action; and 3) analyze structure-function relationships critical for FIC-mediated PTMs and infer from these data determinants of target specificity, type of PTM and mode of regulation. At the forefront of infection biology research, this project is ground-breaking as (i) we will identify a plethora of novel host target PTMs that are critical for a “stealth attack” infection strategy and thus will open new avenues for investigating fundamental mechanisms of persistent infection; and (ii), we will unveil the molecular basis of the remarkable functional versatility of the structurally conserved FIC domain.

1 699 858 €

Start date: 2014-02-01, End date: 2019-01-31

The discovery of the fractional quantum Hall effect created a revolution in solid state research by introducing a new state of matter resulting from strong electron interactions. The new state is characterized by excitations (quasi-particles) that carry fractional charge, which are expected to obey fractional statistics. While odd denominator fractional states are expected to have an abelian statistics, the newly discovered 5/2 even denominator fractional state is expected to have a non-abelian statistics. Moreover, a large number of emerging proposals predict that the latter state can be employed for topological quantum computing ( Station Q was founded by Microsoft Corp. in order to pursue this goal). This proposal aims at studying the abelian and non-abelian fractional charges, and in particular to observe their peculiar statistics. While charges are preferably determined by measuring quantum shot noise, their statistics must be determined via interference experiments, where one particle goes around another. The experiments are very demanding since the even denominator fractions turn to be very fragile and thus can be observed only in the purest possible two dimensional electron gas and at the lowest temperatures. While until very recently such high quality samples were available only by a single grower (in the USA), we have the capability now to grow extremely pure samples with profound even denominator states. As will be detailed in the proposal, we have all the necessary tools to study charge and statistics of these fascinating excitations, due to our experience in crystal growth, shot noise and interferometry measurements.

2 000 000 €

Start date: 2009-01-01, End date: 2013-12-31

"In recent years, the research focus in signal processing has shifted away from the classical linear paradigm, which is intimately linked with the theory of stationary Gaussian processes. Instead of considering Fourier transforms and performing quadratic optimization, researchers are presently favoring wavelet-like representations and have adopted ”sparsity” as design paradigm. Our ambition is to develop a unifying operator-based framework for signal processing that would provide the ``sparse"" counterpart of the classical theory, which is currently missing. To that end, we shall specify and investigate sparse stochastic processes that are continuously-defined and ruled by differential equations, and construct corresponding wavelet-like sparsifying transforms. Our hope is to be able to rigorously connect non-quadratic regularization and sparsity-constrained optimization to well-defined continuous-domain statistical models. We also want to develop a novel Lie-group formalism for the design of steerable, signal-adapted wavelet transforms with improved invariance and sparsifying properties, both in 2-D and 3-D. We shall use these tools to define new reversible image representations in terms of singular points (contours and keypoints) and to develop novel algorithms for 3-D biomedical image analysis. In close collaboration with imaging scientists, we shall apply our framework to the development of new 3-D reconstruction algorithms for emerging bioimaging modalities such as fluorescence deconvolution microscopy, digital holography microscopy, X-ray phase-contrast microscopy, and advanced MRI."

2 106 994 €

Start date: 2011-04-01, End date: 2016-03-31

The gut is the major interface between microbes and their animal hosts and constitutes the main entry route for pathogens. As a consequence gut cells must be armed with efficient immune defenses to combat invasion and colonisation by pathogens. However, the gut also harbors a flora of commensal bacteria, with potentially beneficial effects for the host, which must be tolerated without a chronic, and harmful, immune response. In recent years Drosophila has emerged as a powerful model to dissect host-pathogen interactions, leading to the paradigm of antimicrobial peptide regulation by the Toll and Imd signaling pathways. The strength of this model derives from the availability of powerful and cost effective genetic and genomic tools as well as the high degree of similarities to vertebrate innate immunity. However, in spite of growing interest in gut mucosal immunity generally, very little is known about the immune response of the Drosophila gut. Using powerful new tools and those developed in the study of the systemic response, we propose to raise our understanding of Drosophila gut immunity to the same level as that of systemic immunity within the next five years. This project will involve integrated approaches to dissect not only the gut immune response but also gut homeostasis in the presence of commensal microbiota, as well as strategies used by entomopathogens to circumvent these defenses. We believe that the fundamental knowledge generated on Drosophila gut immunity will serve as a paradigm of epithelial immune reactivity and have a wider impact on our comprehension of animal defense mechanisms.

1 485 627 €

Start date: 2009-04-01, End date: 2014-03-31

This research program originates from a pressing practical need and from a purely new geometric perspective of discrete mathematics.. Graphs play a key role in many application areas of mathematics, providing the perfect mathematical description of all systems that are governed by pairwise interactions, in computer science, economics, biology and more. But graphs cannot fully capture scenarios in which interactions involve more than two agents. Since the theory of hypergraphs is still too under-developed, we resort to geometry and topology, which view a graph as a one-dimensional simplicial complex. I want to develop a combinatorial/geometric/probabilistic theory of higher-dimensional simplicial complexes. Inspired by the great success of random graph theory and its impact on discrete mathematics both theoretical and applied, I intend to develop a theory of random simplicial complexes. This combinatorial/geometric point of view and the novel high-dimensional perspective, shed new light on many fundamental combinatorial objects such as permutations, cycles and trees. We show that they all have high-dimensional analogs whose study leads to new deep mathematical problems. This holds a great promise for real-world applications, in view of the prevalence of such objects in application domains. Even basic aspects of graphs, permutations etc. are much more sophisticated and subtle in high dimensions. E.g., it is a key result that randomly evolving graphs undergo a phase transition and a sudden emergence of a giant component. Computer simulations of the evolution of higher-dimensional simplicial complexes, reveal an even more dramatic phase transition. Yet, we still do not even know what is a higher-dimensional giant component. I also show how to use simplicial complexes (deterministic and random) to construct better error-correcting codes. I suggest a new conceptual approach to the search for high-dimensional expanders, a goal sought by many renowned mathematicians.

1 754 600 €

Start date: 2013-10-01, End date: 2018-09-30

Conduction electrons in the carbon monolayer known as graphene have zero effective mass. This property offers unique opportunities for fast electronics, if we can somehow learn to control the dynamics of particles which have a charge but no mass. Fresh ideas are needed for this purpose, since an electric field is incapable of stopping a massless electron (its velocity being energy independent). The applicant and his group at the Lorentz Institute for Theoretical Physics in Leiden University have started exploring the new physics of graphene soon after the announcement two years ago of the discovery of massless electrons in this material. We have identified several promising control mechanisms, and are now ready to embark on a systematic search. Our objective is to discover ways to manipulate in a controlled manner three independent electronic degrees of freedom: charge, spin, and valley. The charge is the primary carrier of classical information, being strongly coupled to the environment, while the spin is the primary carrier of quantum information, in view of its weak coupling to the environment. The valley degree of freedom (which defines the chirality of the massless particles) is intermediate between charge and spin with regard to the coupling to the environment, and provides some unique opportunities for control. In particular, we have the idea that by acting on the valley rather than on the charge it would be possible to fully block the electronic current (something which an electric field by itself is incapable of). To study these effects we will need to develop new methodologies, since the established methods to model quantum transport in nanostructures are unsuitable for massless carriers.

1 563 800 €

Start date: 2009-06-01, End date: 2013-10-31

T cells display many different phenotypes and functions, depending on the nature of previously encountered signals. If we want to understand how these different T cell subsets arise, we need to be able to follow individual T cells and their progeny through time. With the aim to map the life histories of individual T cells we have developed unique technologies that allow us to determine whether different T cell populations arise from common or distinct progenitors. Within this project we will utilize genetic reporter systems to determine: 1. How T cell recruitment, proliferation and death shape antigen-specific T cell responses 2. At which stage the resulting T cells commit to the effector or the memory T cell lineage 3. The self renewal potential of the tissue-resident memory T cells that remain after infection is cleared By following T cells and their progeny through time, this project will describe the regulation of cell fate in antigen-specific T cell responses. Furthermore, this project will lead to the creation of novel reporters of cellular history that will be of broad value to analyze cell fate and kinship for a variety of cell types.

2 499 640 €

Start date: 2011-05-01, End date: 2017-01-31

An important frontier in condensed matter physics is the understanding of quantum materials in which different ground states compete, leading to electronic inhomogeneity and the concept of ‘quantum electronic liquid crystals’. The challenge for experiments is to measure the local electrodynamic properties in materials, which are electronically inhomogeneous, but atomically homogeneous. I propose a new technique to determine these local variations of the electronic properties. The central objective is to measure with nanometer-scale spatial resolution the frequency-dependent electrodynamic properties, such as complex dielectric constant and complex conductivity of quantum materials at frequencies in the several hundreds of GHz range. The method is derived from the recent progress in astronomical instruments for the submillimeter (hundreds of GHz to THz) frequency band. This progress, to which I contributed extensively, is driven by the desire to study the universe. Now, with this technology and expertise in hand, the disciplinary boundaries can be crossed once more and directed to the other challenging frontier of quantum materials. With this instrument it will become possible to determine the local (and possibly frequency-dependent) electromagnetic properties, such as the dielectric constant and conductivity, for a range of materials. Through this technique, I will make it possible to study the local properties of new materials and even to get access to the local energy-scales of their excitations. It is clear that the program is ambitious and risky, but if successful it provides a major step forward in experiments to reveal the various electronic states of quantum materials and a new scanning-probe technique operating in a new frequency range.

2 451 266 €

Start date: 2014-05-01, End date: 2019-04-30

MicroRNAs (miRNAs) are important regulators of both innate and adaptive immunity. This is very much a frontier area since little is known about miRNA function in vivo, and there is still much discovery to be done. Their emerging functions indicate that they are as potent as cytokines in immunoregulation. We have found that Toll-like receptor (TLR) signaling is potently modulated by 2 particular miRNAs, miR-21 and miR-107. The programme will have 4 aspects which will build on this initial observation. 1. Extension of our observations on miR-21 and TLR signaling. We found that the translational repressor PDCD4 is a key target. We will study miR-21-deficient mice, construct a mouse model where the miR-21 seed sequence in the 3'UTR of PDCD4 is altered, and target miR-21 in vivo using antagomirs. We will also determine the mRNAs regulated by PDCD4 and examine the role of mTOR in PDCD4 control since PDCD4 is a possible substrate. 2. Examination of the role of miR-107 in TLR signaling. TLRs dramatically decrease it¿s expression. We have found that miR-107 has an inhibitory role in TNF secretion via the targeting of CDK6. Activation of PPAR-alpha increases expression of miR107, which could be part of the anti-inflammatory effect of PPAR-alpha ligands. We will explore miR-107-deficient mice and in vitro models of miR-107 function. 3. Exploring the targeting of miR-155 by IL10, which we have recently found. The miR-155 target SHIP1 may be important in this system. We will analyze this process in detail and determine other targets for miR-155 in IL10 action. 4. Perform a screen for novel regulators of the aforementioned miRNAs and screen for miRNAs as regulators of other innate immune pathways, including Nalp3 and RIG-I, about which little is known. These experiments will yield new insights and components The focus is the complex role miRNAs are playing in innate immunity and inflammation.

2 480 587 €

Start date: 2011-06-01, End date: 2016-05-31

Monocytes are central players in inflammation. Progress in understanding their differentiation in target tissues bears potential to manipulate their activities for therapeutic purposes. Here we propose to study the generation of intestinal macrophages (MΦs) as a paradigm, taking advantage of a unique experimental system to elucidate in vivo monocyte fates. The intestine hosts billions of bacteria that assist food uptake, but also pose a challenge, as we have to tolerate these beneficial commensals, yet rapidly mount immune responses to invading pathogens. Failure to maintain this balance causes inflammatory bowel disorders (IBD). Gut resident MΦs are key players in gut homeostasis and inflammation. Here we will study molecular parameters governing their generation from monocytes, as well as their interactions with the immediate tissue surrounding under pathological conditions. We focus on the molecular mechanisms leading to education of monocytes in small and large intestine using genome wide profiling of gene expression, chromatin state and transcription factor binding of monocytes and MΦs. Secondly, we will investigate epithelial and microflora-derived instructing cues, as well as sensory molecules on the MΦs that drive the education. Thirdly, we will study the impact of MΦs that fail to be trained and their role in the development of inflammation. Finally, we will use the insights gained to develop monocyte manipulation strategies that could aid the future development of IBD therapies. Our experimental system allows to follow the in vivo differentiation of engrafted monocytes, as physiological precursor cells, that acquire in a rapid synchronized development in the gut tissue physiologically relevant fates. Expected include (1) fundamental insight into the acquisition and maintenance of MΦ identities in a complex tissue context, (2) progress in our understanding of gut homeostasis and IBD, and (3) guiding insights for future monocyte-targeted therapy.

2 500 000 €

Start date: 2014-01-01, End date: 2018-12-31

Due to their mixed photon-electronic excitation character, cavity polaritons have highly interesting properties. Especially interesting is the so-called ultrastrong coupling regime, reached when the strength of the photon-two-level system coupling is larger than the energy of the resonant state. We have recently demonstrated that terahertz metamaterials coupled to high-mobility two-dimensional electron gases is an almost ideal, field-tunable system that enables the exploration of this ultra-strong coupling regime. In this project, we want to explore four key physical questions opened by this new approach. First we plan to explore the limit of ultra-strong coupling in our systems, including the emission of Casimir-like squeezed vacuum photons upon non-adiabatic change in the coupling energy and parametric generation of light. Secondly we would like to test a theoretical prediction anticipating, in the ultra-strong coupling regime, a quantum phase transition to a Dicke superradiant state upon substitution of the GaAs/AlGaAs two-dimensional electron gas by a graphene layer or multilayers. Thirdly, we claim that our metamaterial-based system also enables the study of coupled polaritons by either direct meta-atom electromagnetic coupling or using a waveguide bus and superconducting circuits. Finally, we want to explore polaritonic emitters and non-linear elements.

2 496 560 €

Start date: 2014-04-01, End date: 2019-03-31

At the boundaries of physics research it is constantly necessary to introduce new tools and methods to expand the horizons and address fundamental issues. In this proposal, we will develop and then apply radically new tools that will enable groundbreaking progress in the field of vortex matter in superconductors and will be of great importance to condensed matter physics and nanoscience. We propose a new scanning magnetic imaging method based on self-aligned fabrication of Josephson junctions with characteristic sizes of 10 nm and superconducting quantum interference devices (SQUID) with typical diameter of 100 nm on the end of a pulled quartz tip. Such nano-SQUID on a tip will provide high-sensitivity high-bandwidth mapping of static and dynamic magnetic fields on nanometer scale that is significantly beyond the state of the art. We will develop a new washboard frequency dynamic microscopy for imaging of site-dependent vortex velocities over a remarkable range of over six orders of magnitude in velocity that is expected to reveal the most interesting dynamic phenomena in vortex mater that could not be investigated so far. Our study will provide a novel bottom-up comprehension of microscopic vortex dynamics from single vortex up to numerous predicted dynamic phase transitions, including disorder-dependent depinning processes, plastic deformations, channel flow, metastabilities and memory effects, moving smectic, moving Bragg glass, and dynamic melting. We will also develop a hybrid technology that combines a single electron transistor with nano-SQUID which will provide an unprecedented simultaneous nanoscale imaging of magnetic and electric fields. Using these tools we will carry out innovative studies of additional nano-systems and exciting quantum phenomena, including quantum tunneling in molecular magnets, spin injection and magnetic domain wall dynamics, vortex charge, unconventional superconductivity, and coexistence of superconductivity and ferromagnetism.

2 000 000 €

Start date: 2008-12-01, End date: 2013-11-30

I propose to study ‘neutral excitations’ in 2d and 1d electronic systems. Such excitations, rarely studied, are unique since they are chargeless but may carry energy. Being byproducts of electron interaction, they come in a few flavors: (i) Downstream modes in composite edge channels of the integer quantum Hall effect (IQHE) regime; (ii) Upstream modes in the fractional quantum Hall effect (FQHE) regime; and (iii) Zero energy Majorana states (localized or propagating quasi-particles), in non-abelian FQHE states and in 1d topological P-wave superconductors. My main interests in neutral modes in the QHE regime are: (a) Their direct association with the nature of the wavefunction of the quantum state; (b) Being excited when a charge mode is being partitioned (say, by a quantum point contact), they may play a prime role in dephasing interference of quasi-particles due to the energy they rob (in the partitioning process). As for detecting Majorana quasi-particles, and aside from the exciting physics, their non-abelian nature makes them attractive as building blocks in ‘decoherence resistant’ systems. Based on our acquired abilities, such as material growth, processing techniques, and sensitive measurement techniques, I plan to perform experiments, which include: thorough studies of downstream and upstream neutral modes via shot noise and thermoelectric current measurements; proving (or disproving) their involvement in dephasing fractionally charged quasi-particles; growing and processing structures that harbor Majorana states (in 1d nano-wires and in 2d FQHE regime; and, possibly, eventually, manipulate Majorana states (by coupling and braiding). Experiments will employ, e.g., ultra-low temperatures, sensitive shot noise measurements, cross-correlation of current fluctuations, and interference of quasi-particles (charge and neutral) in novel interferometers.

2 428 042 €

Start date: 2014-03-01, End date: 2019-02-28

"Liquid-vapor phase transitions and boiling are omnipresent in science and technology, but, as far as basic understanding of the hydrodynamics, these phenomena remain ""terra incognita''. The objective of the proposed work is to achieve a fundamental understanding of the fluid dynamics and heat transfer of the liquid-vapor phase transition - in particular of boiling - both on a micro- and on a macro-scale, through experiments under well-defined and controlled conditions, accompanied by theoretical and numerical modeling. Up to now ""boiling'' has been nearly exclusively an engineering subject. We want to change this and make it a physics subject as we are convinced that boiling involves very interesting and practically relevant physics still in need of understanding. On the micro-scale the planned experiments include nucleation studies of individual and interacting vapor bubbles on superheated, geometrically and chemically micro- and nano-structured surfaces. In the bulk of the flow, nucleation will be achieved through laser heating, through local pressure gradients, and through acoustically triggered vaporization of metastable perfluorcarbon nanodroplets in a superheated liquid. The vapor bubbles will be monitored with ultra-high-speed digital imaging, micro particle velocimetry, infrared thermography, and heat flux measurements. On the theoretical side we will use molecular dynamics simulations and the level-set method. On the macro-scale the focus is on closed boiling turbulent flows, namely Rayleigh-Benard and Taylor-Couette flow. We will measure how the vapor bubble formation affects global quantities such as the heat flux and the angular momentum flux and thus the drag, and local flow properties such as the vapor bubble concentration. The numerical simulations, with one generic code for both geometries, will be based on discrete particle models."

2 108 000 €

Start date: 2011-03-01, End date: 2016-02-29

"The objective of this project is to control the dynamics of a nanoscale object with unprecedented precision and to study interactions on the mesoscale, - the grey zone between the discrete atomistic world and the continuous world of macroscopic objects. A single nanoparticle will be captured by the gradient force of a focused laser beam in ultrahigh vacuum and its center-of-mass motion will be controlled by optical back-action. To cool the nanoparticle to its quantum ground state we will explore active parametric feedback cooling in combination with passive cavity-based cooling. A laser-trapped nanoparticle is physically decoupled from its environment, which guarantees extremely long coherence times and quality factors as high as 10^11 in ultrahigh vacuum. Force sensitivities of 10^(-20) Newtons in a bandwidth of 1 Hz can be achieved, which outperforms other measurement techniques by orders of magnitude. In this project, we will use a laser-trapped nanoparticle as a local probe for measuring mesoscopic interactions, such as Casimir forces, vacuum friction, non-equilibrium dynamics and phase transitions, with unprecedented accuracy. We will also measure the dynamics of nanoparticles in double-well potentials created by two laser beams with closely spaced foci. A pair of trapped nanoparticles defines a highly controllable coupled-oscillator model, which can be used for studying strong coupling, level splitting, and adiabatic energy transfer at the quantum - classical barrier. A nanoparticle cooled to its quantum ground state opens up a plethora of fundamental studies, such as the collapse of quantum superposition states under the influence of noise and gravity-induced quantum state reduction. This project will also open up new directions for precision metrology and provide unprecedented control over the dynamics of matter on the nanometer scale."

2 499 471 €

Start date: 2013-10-01, End date: 2018-09-30

We propose to develop an opto-electronics interface between single-electron devices and single-photon optics. The ultimate limit in the miniaturization of electronics and photonics is at the nanometer scale. Here the signal level can be controlled at the fundamental level of a single electron for electricity and a single photon for light. These limits are actively being pursued for scientific interest with possible applications in the new area of quantum information science. Yet, these efforts occur separately in the distinct communities of solid state electronics and quantum optics. Here we propose to develop a toolbox for interfacing electronics and optics on the level of single electrons and photons. The basic building block is a nanoscale pn-junction defined in a semiconductor nanowire, which is the most versatile material system for single electron to single photon conversion. We will develop the following technology: (1) growth of complex semiconductor nanowires (2) quantum state transfer for copying the information stored in an electron quantum state onto a photon state (3) single-photon optical-chip with on-chip guiding via single plasmons and on-chip detection with a superconducting detector. Besides being fundamentally interesting by itself, this new toolbox opens a new area of experiments where qubits processed in solid state nano-devices are coupled quantum mechanically over long distances via photons as signal carriers to various kinds of other interesting quantum system (e.g. solid state quantum dots, confined nuclear spins and atomic vapours).

1 800 000 €

Start date: 2009-01-01, End date: 2013-10-31

"Our proposal has three components: 1. Unitarizable representations. 2. Spaces and groups of non-positive curvature. 3. Bounds for characteristic classes. The three parts are independent and each one is justified by major well-known conjectures and/or ambitious goals. Nevertheless, there is a unifying theme: Group Theory and its relations to Geometry, Dynamics and Analysis. In the first part, we study the Dixmier Unitarizability Problem. Even though it has remained open for 60 years, it has witnessed deep results in the last 10 years. More recently, the PI and co-authors have obtained new progress. Related questions include the Kadison Conjecture. Our methods are as varied as ergodic theory, random graphs, L2-invariants. In the second part, we study CAT(0) spaces and groups. The first motivation is that this framework encompasses classical objects such as S-arithmetic groups and algebraic groups; indeed, the PI obtained new extensions of Margulis' superrigidity and arithmeticity theorems. We are undertaking an in-depth study of the subject, notably with Caprace, aiming at constructing the full ""semi-simple theory"" in the most general setting. This has many new consequences even for the most classical objects such as matrix groups, and we propose several conjectures as well as the likely methods to attack them. In the last part, we study bounded characteristic classes. One motivation is the outstanding Chern Conjecture, according to which closed affine manifolds have zero Euler characteristic. We propose a strategy using a range of techniques in order to either attack the problem or at least obtain new results on simplicial volumes."

1 332 710 €

Start date: 2011-03-01, End date: 2016-02-29

Today superconducting electronic circuits are one of the prime physical systems to explore both foundations and technological applications of quantum mechanics.The concept of processing information more efficiently using quantum mechanics has stimulated enormous progress in control and measurement of quantum electronic circuits. Now such circuits are one of the prime contenders for realizing a viable quantum information processor. Similarly, the realization of strong coherent interactions between superconducting quantum bits and individual photons has stimulated a wide range of research exploring quantum optics in these systems. In this project we plan to investigate quantum communication using superconducting circuits, an area altogether unexplored in this domain. For this purpose we will develop both hardware and experimental techniques to realize superconducting quantum networks across distances of tens of meters. In contrast to existing experiments in which quantum information is distributed over millimeter distances only, realizing such networks will allow us to address both fundamental and practical questions. In particular, we will create and test networking architectures for superconducting quantum information processors, we will create entanglement over distances on meter length-scales and perform Bell-tests of space-like separated objects with high detection efficiency. We also plan to realize and test elements for quantum repeaters and to explore ideas of blind quantum computation. The remarkable progress in quantum technologies based on superconducting circuits, including more than 5 orders of magnitude improvement in coherence over the last 13 years, contributes to the great potential of these systems for applications. The challenging realization of quantum networks covering larger distances will contribute to expand the range of fundamental questions addressable and applications conceivable in superconducting quantum technologies.

3 242 977 €

Start date: 2014-09-01, End date: 2019-08-31

The number one question in ecology is why certain organisms occur where they do, and what the traits are which make them successful. This project aims at arriving at a functional explanation of the climatic limits of major European broad leaved tree taxa. It will focus on and explore their temperature-related limits and aims at reviving Europe's traditional strength in physiology based ecology by training a group of young scientists to answer such questions. The project builds upon many years of the PIs experience in mechanism oriented ecology (e.g. synthesis in Körner 2003) and should help trading those rapidly disappearing skills to a next generation of experimental ecologists. The project adopts a three-step approach: (1) Assess the current extreme postions of tree taxa along thermal gradients, using existing data bases and site visits (data mining, biogeography). (2) Associate those patterns with bioclimatic information, both available and newly acquired (climatology). (3) Empirically test hypotheses of causes of growth limitation and stress survival, both in the field and in the laboratory (eco-physiology). The project will account for ecotypic differentiation by using the uppermost (marginal) and central (optimal) positions of taxa and will explore plant establishment as well as adult plant performance. It will use in situ measurements, transplant and common gardens as well as phytotron testing. Genotypic control of phenology, frost hardiness, thermal constraints of growth and reproduction (fitness) will play a central role. The results will, for the first time, offer a mechanistic (rather then correlative) explanation for broad leaf tree species distribution in Europe and thus, will provide a basis for improved parameterization and evaluation of species distribution models in a climate change context.

1 249 198 €

Start date: 2009-04-01, End date: 2014-03-31

Viruses are simple, obligatory, intracellular parasites that depend on the host cell for most of the steps in the replication cycle. Not only do they rely on the cells biosynthetic machinery, they exploit cellular processes for signaling, membrane trafficking, intra-cellular transport, nuclear import and export, molecular sorting, transcriptional regulation, etc. To access the full spectrum of host cell functions in the infection of three different viruses in an unbiased and systematic fashion, we will identify the critical host cell proteins needed by monitoring infection in human tissue culture cells after silencing individual genes using genome-wide siRNA libraries and large sub-libraries based on the human genome. The three viruses are vaccinia virus (a poxvirus), human papilloma virus 16, and Uukuniemi virus (a bunyavirus). They are members of important but poorly analyzed pathogen families representing enveloped and nonenveloped viruses, RNA and DNA viruses, viruses that replicate in the nucleus and in the cytosol. The infection assays to be used are fully automated, and make use of high-content microscopic read-outs for infection and virus production. Identification of the viral infectomes , in this way, offers a valuable, new perspective into the complexities of the infection process, and opens wide new areas of basic and applied research. After validation of hits , extensive biochemical and cell biological analysis will be performed on a selected set of host proteins and pathways identified through the infectome analysis. We will determine which steps in the replication cycle are affected, which mechanisms are involved, and which cellular pathways play a role. For detailed analysis, we will focus on mechanisms in entry, uncoating, and early intracellular events. A large spectrum of techniques including live cell imaging and single particle tracking will be used to follow up the screening results with functional and mechanistic studies.

2 498 400 €

Start date: 2009-02-01, End date: 2014-01-31