ERC FUNDED PROJECTS

State-of-the-art microscopy and diffraction imaging provides insight into the atomic and sub-atomic structure of matter. They permit determination of the positions of atoms in a crystal lattice or in a molecule as well as the distribution of electrons inside atoms. State-of-the-art time-resolved spectroscopy with femtosecond and attosecond resolution provides access to dynamic changes in the atomic and electronic structure of matter. Our proposal aims at combining these two frontier techniques of XXI century science to make a long-standing dream of scientist come true: the direct observation of atoms and electrons in their natural state: in motion. Shifts in the atoms positions by tens to hundreds of picometers can make chemical bonds break apart or newly form, changing the structure and/or chemical composition of matter. Electronic motion on similar scales may result in the emission of light, or the initiation of processes that lead to a change in physical or chemical properties, or biological function. These motions happen within femtoseconds and attoseconds, respectively. To make them observable, we need a 4-dimensional (4D) imaging technique capable of recording freeze-frame snapshots of microscopic systems with picometer spatial resolution and femtosecond to attosecond exposure time. The motion can then be visualized by slow-motion replay of the freeze-frame shots. The goal of this project is to develop a 4D imaging technique that will ultimately offer picometer resolution is space and attosecond resolution in time.

2 500 000 €

Start date: 2010-03-01, End date: 2015-02-28

Some of the most extreme tests of physical law come from its manifestations in the behaviour of black holes and neutron stars, and as such these objects should be used as fundamental physics labs. Due to advances in both theoretical work and observational techniques, I have a major opportunity now to significantly push this agenda forward and get better answers to questions like: How are black holes born? How can energy be extracted from black holes? What is the origin of magnetic fields and cosmic rays in jets and shocks? Is their primary energy stream hadronic or magnetic? I propose to do this by exploiting the advent of wide-field radio astronomy: extreme objects are very rare and usually transient, so not only must one survey large areas of sky, but also must one do this often. I propose to form and shape a group that will use the LOFAR wide-field radio telescope to hunt for these extreme transients and systematically collect enough well-documented examples of the behaviour of each type of transient. Furthermore, I propose to expand LOFAR with a true 24/7 all-sky monitor to catch and study even the rarest of events. Next, I will use my experience in gamma-ray burst followup to conduct a vigorous multi-wavelength programme of study of these objects, to constrain their physics from as many angles as possible. This will eventually include results from multi-messenger astrophysics, in which we use neutrinos, gravity waves, and other non-electromagnetic messengers as extra diagnostics of the physics of these sources. Finally, I will build on my experience in modelling accretion phenomena and relativistic explosions to develop a theoretical framework for these phenomena and constrain the resulting models with the rich data sets we obtain.

3 499 128 €

Start date: 2010-10-01, End date: 2016-09-30

A significant advance in the field of development has been the appreciation that radial glial cells are progenitors and give birth to neurons in the brain. In order to advance this exciting area of biology, we need approaches that combine structural and functional studies of these cells. This is reflected by the emerging realisation that dynamic interactions involving radial glia may be critical for the regulation of their proliferative behaviour. It has been observed that radial glia experience transient elevations in intracellular Ca2+ but the nature of these signals, and the information that they convey, is not known. The inability to observe these cells in vivo and over the course of their development has also meant that basic questions remain unexplored. For instance, how does the behaviour of a radial glial cell at one point in development, influence the final identity of its progeny? I propose to build a research team that will capitalise upon methods we have developed for observing individual radial glia and their progeny in an intact vertebrate nervous system. The visual system of Xenopus Laevis tadpoles offers non-invasive optical access to the brain, making time-lapse imaging of single cells feasible over minutes and weeks. The system s anatomy lends itself to techniques that measure the activity of the cells in a functional sensory network. We will use this to examine signalling mechanisms in radial glia and how a radial glial cell s experience influences its proliferative behaviour and the types of neuron it generates. We will also examine the interactions that continue between a radial glial cell and its daughter neurons. Finally, we will explore the relationships that exist within neuronal progeny derived from a single radial glial cell.

1 284 808 €

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

The aim of this project is the realisation of efficient mid-infrared and THz optoelectronic emitters. This work is motivated by the fact that the spontaneous emission in this frequency range is characterized by an extremely long lifetime when compared to non-radiative processes, giving rise to devices with very low quantum efficiency. To this end we want to develop hybrid light-matter systems, already well known in quantum optics, within optoelectronics devices, that will be driven by electrical injection. With this project we want to extend the field of optoelectronics by introducing some of the concepts of quantum optic, particularly the light-matter strong coupling, into semiconductor devices. More precisely this project aims at the implementation of novel optoelectronic emitters operating in the strong coupling regime between an intersubband excitation of a two-dimensional electron gas and a microcavity photonic mode. The quasiparticles issued from this coupling are called intersubband polaritons. The major difficulties and challenges of this project, do not lay in the observation of these quantum effects, but in their exploitation for a specific function, in particular an efficient electrical to optical conversion. To obtain efficient quantum emitters in the THz frequency range we will follow two different approaches: - In the first case we will try to exploit the additional characteristic time of the system introduced by the light-matter interaction in the strong (or ultra-strong) coupling regime. - The second approach will exploit the fact that, under certain conditions, intersubband polaritons have a bosonic character; as a consequence they can undergo stimulated scattering, giving rise to polaritons lasers as it has been shown for excitonic polaritons.

1 761 000 €

Start date: 2010-05-01, End date: 2015-04-30

The role of the African continent in the global carbon cycle, and therefore in climate change, is increasingly recognised. Despite the increasingly acknowledged importance of Africa in the global carbon cycle and its high vulnerability to climate change there is still a lack of studies on the carbon cycle in representative African ecosystems (in particular tropical forests), and on the effects of climate on ecosystem-atmosphere exchange. In the present proposal we want to focus on these spoecifc objectives : 1. Understand the role of African tropical rainforest on the GHG balance of the atmosphere and revise their role on the global methane and N2O emissions. 2. Determine the carbon source/sink strength of African tropical rainforest in the pre-industrial versus the XXth century by temporal reconstruction of biomass growth with biogeochemical markers 3. Understand and quantify carbon and GHG fluxes variability across African tropical forests (west east equatorial belt) 4.Analyse the impact of forest degradation and deforestation on carbon and other GHG emissions

2 406 950 €

Start date: 2010-04-01, End date: 2014-12-31

Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.

1 727 920 €

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

Understanding the molecular mechanisms underlying adipose blood vessel growth or regression opens new fundamentally insight into novel therapeutic options for the treatment of obesity and its related metabolic diseases such as type 2 diabetes and cancer. Unlike any other tissues in the body, the adipose tissue constantly experiences expansion and shrinkage throughout the adult life. Adipocytes in the white adipose tissue have the ability to switch into metabolically highly active brown-like adipocytes. Brown adipose tissue (BAT) contains significantly higher numbers of microvessels than white adipose tissue (WAT) in order to adopt the high rates of metabolism. Thus, an angiogenic phenotype has to be switched on during the transition from WAT into BAT. We have found that acclimation of mice in cold could induce transition from inguinal and epidedymal WAT into BAT by upregulation of angiogenic factor expression and down-regulations of angiogenesis inhibitors (Xue et al, Cell Metabolism, 2009). The transition from WAT into BAT is dependent on vascular endothelial growth factor (VEGF) that primarily targets on vascular endothelial cells via a tissue hypoxia-independent mechanism. VEGF blockade significantly alters adipose tissue metabolism. In another genetic model, we show similar findings that angiogenesis is crucial to mediate the transition from WAT into BAT (Xue et al, PNAS, 2008). Here we propose that the vascular tone determines the metabolic switch between WAT and BAT. Characterization of these novel angiogenic pathways may reveal new mechanisms underlying development of obesity- and metabolism-related disease complications and may define novel therapeutic targets. Thus, the benefit of this research proposal is enormous and is aimed to treat the most common and highly risk human health conditions in the modern time.

2 411 547 €

Start date: 2010-03-01, End date: 2015-02-28

RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA (dsRNA). One of the functions of this pathway is the defense against parasitic nucleic acids: transposons and viruses. Previous results demonstrated that viral infections in Drosophila melanogaster are fought by an antiviral RNAi response and that components of the endocytic pathway are required for dsRNA entry to initiate the RNAi response. Recently we have shown that infected insect cells spread a systemic silencing signal that elicits a protective RNAi-dependent immunity throughout the organism. This suggests that the cell-autonomous RNAi response is insufficient to control a viral infection and that flies also rely on systemic immune response to fight against such infections. As a junior group leader, I will study the mechanisms that mediate the RNAi-based antiviral response in insects. By combining biochemical, cellular, molecular and genomic approaches, both in vivo and in cell culture, I will analyze the mechanisms underlying viral tropism, systemic propagation of the antiviral signal and the basis of the persistence of the antiviral state. Furthermore, I will examine whether the dsRNA-uptake pathway is conserved in mosquitoes and its relationship with viral immunity in that host. This comprehensive approach will tackle how this nucleic acid-based immunity works in insects to generate an anti-viral stage. A better understanding of the role of RNA silencing in insects during virus infection will allow the exploitation of this pathway for improvement of public health related problems such as arbovirus infection and disease.

1 900 000 €

Start date: 2009-10-01, End date: 2014-12-31

The goal of this project is to prepare in a deterministic way, and then to characterize, various entangled states of up to 25 individual atoms held in an array of optical tweezers. Such a system provides a new arena to explore quantum entangled states of a large number of particles. Entanglement is the existence of quantum correlations between different parts of a system, and it is recognized as an essential property that distinguishes the quantum and the classical worlds. It is also a resource in various areas of physics, such as quantum information processing, quantum metrology, correlated quantum systems and quantum simulation. In the proposed design, each site is individually addressable, which enables single atom manipulation and detection. This will provide the largest entangled state ever produced and fully characterized at the individual particle level. The experiment will be implemented by combining two crucial novel features, that I was able to demonstrate very recently: first, the manipulation of quantum bits written on long-lived hyperfine ground states of single ultra-cold atoms trapped in microscopic optical tweezers; second, the generation of entanglement by using the strong long-range interactions between Rydberg states. These interactions lead to the so-called dipole blockade , and enable the preparation of various classes of entangled states, such as states carrying only one excitation (W states), and states analogous to Schrödinger s cats (GHZ states). Finally, I will also explore strategies to protect these states against decoherence, developed in the framework of fault-tolerant and topological quantum computing. This project therefore combines an experimental challenge and the exploration of entanglement in a mesoscopic system.

1 449 600 €

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

Our aim is to provide a theoretical framework for studies of dynamical aspects of magnetic materials and magnetisation reversal, which has potential for applications for magnetic data storage and magnetic memory devices. The project focuses on developing and using an atomistic spin dynamics simulation method. Our goal is to identify novel materials and device geometries with improved performance. The scientific questions which will be addressed concern the understanding of the fundamental temporal limit of magnetisation switching and reversal, and the mechanisms which govern this limit. The methodological developments concern the ability to, from first principles theory, calculate the interatomic exchange parameters of materials in general, in particular for correlated electron materials, via the use of dynamical mean-field theory. The theoretical development also involves an atomistic spin dynamics simulation method, which once it has been established, will be released as a public software package. The proposed theoretical research will be intimately connected to world-leading experimental efforts, especially in Europe where a leading activity in experimental studies of magnetisation dynamics has been established. The ambition with this project is to become world-leading in the theory of simulating spin-dynamics phenomena, and to promote education and training of young researchers. To achieve our goals we will build up an open and lively environment, where the advances in the theoretical knowledge of spin-dynamics phenomena will be used to address important questions in information technology. In this environment the next generation research leaders will be fostered and trained, thus ensuring that the society of tomorrow is equipped with the scientific competence to tackle the challenges of our future.

2 130 000 €

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

Atherosclerosis is characterized by chronic inflammation of the arterial wall. Mononuclear cell recruitment is driven by chemokines that can be deposited e.g. by activated platelets on inflamed endothelium. Chemokines require oligomerization and immobilization for efficient function, and recent evidence supports the notion that heterodimer formation between chemokines constitutes a new regulatory principle amplifying specific chemokine activities while suppressing others. Although crucial to inflammatory disease, this has been difficult to prove in vivo, primarily as chemokine heterodimers exist in equilibrium with their homodimer counterparts. We introduce the paradigm that heteromerization of chemokines provides the combinatorial diversity for functional plasticity and fine-tuning, coining this interactome. Given the relevance of chemokine heteromers in vivo, we aim to exploit this in an anti-inflammatory approach to selectively target vascular disease. In a multidisciplinary project, we plan to generate covalently-linked heterodimers to establish their biological significance. Obligate heterodimers of CC and CXC chemokines will be designed using computer-assisted modeling, chemically synthesized and cross-linked, structurally assessed using NMR spectroscopy and crystallography, and subjected to functional characterization in vitro and reconstitution in vivo. Conversely, we will develop cyclic beta-sheet-based peptides binding chemokines to specifically disrupt heteromers and we will generate mice with conditional deletion or knock-in of chemokine mutants with defects in heteromerization or proteoglycan binding to be analyzed in models of atherosclerosis. Peptides will be used for molecular imaging and chemokine heteromers will be quantified in cardiovascular patients.

2 500 000 €

Start date: 2010-04-01, End date: 2016-03-31

We propose to investigate a new frontier in Physics: the study of Magnetic systems using attosecond laser pulses. The main disciplines concerned are: Ultrafast laser sciences, Magnetism and Spin-Photonics, Relativistic Quantum Electrodynamics. Three issues of modern magnetism are addressed. 1. How fast can one modify and control the magnetization of a magnetic system ? 2. What is the role and essence of the coherent interaction between light and spins ? 3. How far spin-photonics can bring us to the real world of data acquisition and storage ? - We want first to provide solid ground experiments, unravelling the mechanisms involved in the demagnetization induced by laser pulses in a variety of magnetic materials (ferromagnetic nanostructures, aggregates and molecular magnets). We will explore the ultrafast magnetization dynamics of magnets using an attosecond laser source. - Second we want to explore how the photon field interacts with the spins. We will investigate the dynamical regime when the potential of the atoms is dressed by the Coulomb potential induced by the laser field. A strong support from the relativistic Quantum Electro-Dynamics is necessary towards that goal. - Third, even though our general approach is fundamental, we want to provide a benchmark of what is realistically possible in ultrafast spin-photonics, breaking the conventional thought that spin photonics is hard to implement at the application level. We will realize ultimate devices combining magneto-optical microscopy with the conventional magnetic recording. This new field will raise the interest of a number of competitive laboratories at the international level. Due to the overlapping disciplines the project also carries a large amount of educational impact both fundamental and applied.

2 492 561 €

Start date: 2010-05-01, End date: 2015-04-30

This project has the potential to radically change current understanding of cultic and social transformation in the post-exilic temple community of Jerusalem (c. 6th-4th centuries BCE), an important formative phase of ancient Judaism. “BABYLON” draws on recent, ground-breaking advances in the study of cuneiform texts to illuminate the Babylonian environment of the Judean exile, the socio-historical context which gave rise to the transformative era in Second Temple Judaism. In particular, these new data show that the parallels between Babylonian and post-exilic forms of cultic and social organization were substantially more far-reaching than presently recognized in Biblical scholarship. “BABYLON” will study the extent of these similarities and explore the question how Babylonian models could have influenced the restoration effort in Jerusalem. This goal will be achieved through four sub-projects. P1 will study the social dynamics and intellectual universe of the Babylonian priesthood. P2 will finalize the publication of cuneiform archives of Babylonian priests living in the time of the exile. P3 will identify the exact areas of change in the post-exilic temple community of Jerusalem. P4, the synthesis, will draw from each of these sub-projects to present a comparative study of the Second Temple and contemporary Babylonian models of cultic and social organization, and to propose a strategy of research into the possible routes of transmission between Babylonia and Jerusalem. The research will be carried out by three team members: the PI (P1 and P4), a PhD in Assyriology (P2) and a post-doctoral researcher in Biblical Studies specialized in the Second Temple period (P3 and P4). The participation of the wider academic community will be invited at two moments in the course of the project, in the form of a workshop and an international conference. “BABYLON” will adopt an interdisciplinary approach by bringing together Assyriologists and Biblical scholars for a much-needed dialogue, thereby exploding the artificial boundaries that currently exist in the academic landscape between these two fields.

1 200 000 €

Start date: 2009-09-01, End date: 2015-08-31

The proposed research entails an ethnographic study of two contemporary cases of post-conflict reconciliation: one, the Bosnian case, where international intervention ended conflict in a stalemate and went on to instigate a decade-long process of transition; and the other, the Spanish case, where a nationally-contrived pact of silence introduced an overnight transition after Franco's death a pact now being broken nearly seventy years after the country's civil war concluded. Both societies witnessed massive violations of international humanitarian law. Both societies are presently exhuming, identifying and re-burying their dead. But their trajectories of transitional justice could not have been more different. This project will investigate how Law shapes cultural memories of wartime atrocity in these contrasting scenarios. How do criminal prosecutions, constitutional reforms, and international rights mechanisms, provide or obfuscate the scales into which histories of violent conflict are framed? Does the systematic re-structuring of legislative and judicial infrastructure stifle recognition of past abuses or does it create the conditions through which such pasts can be confronted? How does Law shape or inflect the cultural politics of memory and memorialisation? And most importantly, how should legal activity be weighted, prioritised and sequenced with other, extra-legal components of peace-building initiatives? The ultimate goal of this project will be to mobilise the findings from the two field-sites to suggest a more nuanced assessment of Law s place in transitional justice. Arguing that disparate historical, cultural and legal contexts require equally distinct approaches towards social healing, the research aims to produce a Post-Conflict Action Framework an architecture of questions and concerns, which, once answered, would point towards context-specific designs for transitional justice programmes in the future.

1 420 000 €

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

Telomeres are heterochromatic nucleoprotein complexes located at the end of linear eukaryotic chromosomes. Contrarily to a longstanding dogma, we have recently demonstrated that mammalian telomeres are transcribed into TElomeric Repeat containing RNA (TERRA) molecules. TERRA transcripts contain telomeric RNA repeats and are produced at least in part by DNA-dependent RNA polymerase II-mediated transcription of telomeric DNA. TERRA molecules form discrete nuclear foci that co-localize with telomeric heterochromatin in both interphase and transcriptionally inactive metaphase cells. This indicates that TERRA is an integral component of telomeres and suggests that TERRA might participate in maintaining proper telomere heterochromatin. We will use a variety of biochemistry, cell biology, molecular biology and microscopy based approaches applied to cultured mammalian cells and to the yeast Schizosaccharomyces pombe, to achieve four distinct major goals: i) We will over-express or deplete TERRA in mammalian cells in order to characterize the molecular details of putative TERRA-associated functions in maintaining normal telomere structure and function; ii) We will locate TERRA promoter regions on different human chromosome ends; iii) We will generate mammalian cellular systems in which to study artificially seeded telomeres that can be transcribed in an inducible fashion; iv) We will identify physiological regulators of TERRA by analyzing it in mammalian cultured cells where the functions of candidate factors are compromised. In parallel, taking advantage of the recent discovery of TERRA also in fission yeast, we will systematically analyze TERRA levels in fission yeast mutants derived from a complete gene knockout collection. The study of TERRA regulation and function at chromosome ends will strongly contribute to our understanding of how telomeres are maintained and will help to clarify the general functions of mammalian non-coding RNAs.

1 602 600 €

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

This interdisciplinary proposal has the objective to greatly enhance our understanding of fundamental biomineralization processes involved in the formation of calcium carbonates by marine organisms, such as corals, foraminifera and bivalves, in order to better understand vital effects. This is essential to the application of these carbonates as proxies for global (paleo-) environmental change. The core of the proposal is an experimental capability that I have pioneered during 2008: Dynamic stable isotopic labeling during formation of carbonate skeletons, tests, and shells, combined with NanoSIMS imaging. The NanoSIMS ion microprobe is a state-of-the-art analytical technology that allows precise elemental and isotopic imaging with a spatial resolution of ~100 nanometers. NanoSIMS imaging of the isotopic label(s) in the resulting biocarbonates and in associated cell-structures will be used to uncover cellular-level transport processes, timescales of formation of different biocarbonate components, as well as trace-elemental and isotopic fractionations. This will uncover the origin of vital effects. With this proposal, I establish a new scientific frontier and guarantee European leadership. The technical and scientific developments resulting from this work are broadly applicable and will radically change scientific ideas about marine carbonate biomineralization and compositional vital effects.

2 182 000 €

Start date: 2010-07-01, End date: 2015-06-30

One of the most fundamental issues in evolutionary biology is the nature of transitions from single cell organisms to multicellular ones, with accompanying cellular differentiation and specialization. Not surprisingly for microscopic life in fluid environments, many of the relevant physical considerations involve diffusion, mixing, and sensing, for the efficient exchange of nutrients and metabolites with the environment is one of the most basic features of life. This proposal describes a combination of experimental and theoretical research aimed at some of the key mysteries surrounding transport and sensing by and in complex, multicellular organisms, and the implications of those findings for the explanation of driving forces behind transitions to multicellularity. There are two main components of the research. The first involves studies of single and multicellular algae which serves as model systems for allometric scaling laws in evolution. Of particular importance are the synchronization dynamics of the eukaryotic flagella that provide motility, enhance nutrient transport, and allow phototaxis in these organisms. The second thrust involves investigation of the ubiquitous phenomenon of cytoplasmic streaming in aquatic and terrestrial plants. Despite decades of research, there is no clear consensus on the metabolic role of this persistent circulation of the fluid contents of cell. Building on recent theoretical developmnts we will study its implications for internal transport and mixing, homeostasis, and development in large cells. In each case, state-of-the art experimental methods from physics, fluid dynamics, and cell biology will be used in combination with advanced theoretical methods for the study of the stochastic nonlinear PDEs that form the natural description of these systems.

2 500 000 €

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

The biomembrane is a prerequisite of life. It enables the cell to maintain a controlled environment and to establish electrochemical gradients as rapidly accessible energy stores. Biomembranes also provide scaffold for organisation and spatial definition of signal transmission in the cell. Crystal structures of membrane proteins are determined with an increasing pace. Along with functional studies integral studies of individual membrane proteins are now widely implemented. The BIOMEMOS proposal goes a step further and approaches the function of the biomembrane at the higher level of membrane protein complexes. Through a combination of X-ray crystallography, electrophysiology, general biochemistry, biophysics and bioinformatics and including also the application of single-particle cryo-EM and small-angle X-ray scattering, the structure and function of membrane protein complexes of key importance in life will be investigated. The specific targets for investigation in this proposal include: 1) higher-order complexes of P-type ATPase pumps such as signalling complexes of Na+,K+-ATPase, and 2) development of methods for structural studies of membrane protein complexes Based on my unique track record in structural studies of large, difficult structures (ribosomes and membrane proteins) in the setting of a thriving research community in structural biology and biomembrane research in Aarhus provides a critical momentum for a long-term activity. The activity will take advantage of the new possibilities offered by synchrotron sources in Europe. Furthermore, a single-particle cryo-EM research group formed on my initiative in Aarhus, and a well-established small-angle X-ray scattering community provides for an optimal setting through multiple cues in structural biology and functional studies

2 444 180 €

Start date: 2010-04-01, End date: 2015-03-31

This project addresses a key issue in fundamental research - one that has challenged ecologists ever since Darwin s time that is why some species are common, and others rare, and why, despite marked turnover at the level of individual species abundances, the structure of a community is generally conserved through time. Its aim is to examine the temporal dynamics of species abundance distributions (SADs), and to assess the capacity of these distributions to withstand change (resistance) and to recover from change (resilience). These are topical and important questions given the increasing impact that humans are having on the natural world. There are three components to the research. First, we will model SADs and predict responses to a range of events including climate change and the arrival of invasive species. A range of modeling approaches (including neutral, niche and statistical) will be adopted; by incorporating temporal turnover in hitherto static models we will advance the field. Second, we will test predictions concerning the resistance and resilience of SADs by a comparative analysis of existing data sets (that encompass communities in terrestrial, freshwater and marine environments for ecosystems extending from the poles to the tropics) and through a new field experiment that quantifies temporal turnover across a community (unicellular organisms to vertebrates) in relation to factors both natural (dispersal limitation) and anthropogenic (human disturbance) thought to shape SADs. In the final part of the project we will apply these new insights into the temporal dynamics of SADs to two important conservation challenges. These are 1) the conservation of biodiversity in a heavily utilized European landscape (Fife, Scotland) and 2) the conservation of biodiversity in Mamirauá and Amaña reserves in Amazonian flooded forest. Taken together this research will not only shed new light on the structure of ecological communities but will also aid conservation.

1 812 782 €

Start date: 2010-08-01, End date: 2016-01-31

The aim of the proposed project is to shed light on early childhood gender-differentiated socialization and gender-specific susceptibility to parenting within families in relation to disruptive behaviour in boys and girls in the first four years of life. The popular saying boys will be boys refers to the observation that boys show more disruptive behaviours (e.g., noncompliance or aggression) than girls, a pattern that has been confirmed frequently in scientific research. There is also evidence that parents treat boys differently from girls in ways that are likely to foster boys disruptive behaviour, and that boys are more susceptible to problematic family functioning than girls. The crucial question is whether gender differences in socialization, susceptibility to socialization, and children s behavioural outcomes are also salient when the same parents are doing the parenting of both a boy and a girl. Within-family comparisons are necessary to account for structural differences between families. To this end, families with two children born 22-26 months apart will be recruited from the general population. To account for birth order and gender-combination effects, the sample includes four groups of 150 families each, with the following sibling combinations: girl-boy, boy-girl, girl-girl, and boy-boy. The study has a four-wave longitudinal design, based on the youngest sibling with assessments at ages 12, 24, 36, and 48 months, because gender differences in disruptive behaviour develop during the toddler years. Each assessment consists of two home visits: one with mother and one with father, including observations of both children and of the children separately. Parenting behaviours will be studied in reaction to specific child behaviours, including aggression, noncompliance, and prosocial behaviours.

1 611 970 €

Start date: 2010-02-01, End date: 2015-03-31

Energy, supplied in the form of oxygen and glucose in the blood, is essential for the brain s cognitive power. Failure of the energy supply to the nervous system underlies the mental and physical disability occurring in a wide range of economically important neurological disorders, such as stroke, spinal cord injury and cerebral palsy. Using a combination of two-photon imaging, electrophysiological, molecular and transgenic approaches, I will investigate the control of brain energy supply at the vascular level, and at the level of individual neurons and glial cells, and study the deleterious consequences for the neurons, glia and vasculature of a failure of brain energy supply. The work will focus on the following fundamental issues: A. Vascular control of the brain energy supply (1) How important is control of energy supply at the capillary level, by pericytes? (2) Which synapses control blood flow (and thus generate functional imaging signals) in the cortex? B. Neuronal and glial control of brain energy supply (3) How is grey matter neuronal activity powered? (4) How is the white matter supplied with energy? C. The pathological consequences of a loss of brain energy supply (5) How does a fall of energy supply cause neurotoxic glutamate release? (6) How similar are events in the grey and white matter in energy deprivation conditions? (7) How does a transient loss of energy supply affect blood flow regulation? (8) How does brain energy use change after a period without energy supply? Together this work will significantly advance our understanding of how the energy supply to neurons and glia is regulated in normal conditions, and how the loss of the energy supply causes disorders which consume more than 5% of the costs of European health services (5% of ~1000 billion euro/year).

2 499 947 €

Start date: 2010-04-01, End date: 2016-03-31

Predation plays a major role in energy and nutrient flow in the biological food chain. Carnivory is best known from the animal kingdom, but the plant kingdom has flesh eaters as well. This field has attracted much interest since Darwin s time, but many fundamental properties of the carnivorous life style remain largely unexplored. This project will close this gap by a multidisciplinary approach based on state-of-art bioinformatics, molecular biology, chemistry and biophysics. It will focus on 1. Genome/Transcriptome Profiling to study the genetic make-up of carnivorous plants (CPs) and the evolution of carnivory 2. Origin of Excitability to investigate whether CPs gained the inventory to fire action potentials from captured animals or rather evolved excitability independently 3. Prey Recognition on the basis of mechanical- and chemical senses 4. Endocrinology Structure and function of exocrine glands - CPs offer a unique system to study the biology of digestive glands (exo-/endocytosis) in plants. Over 600 plant species use special structures to capture animals such as insects. The genome/transcriptome of major trap types such as snap traps, tentacles traps, suction traps, corkscrew traps, and pitfall traps will be compared and trap-specific genes identified. Among them those giving rise to membrane excitation, excitation-contraction coupling and exocrine systems (glands) will be functionally characterized in detail. Using loss-of-function mutants and transformed plants with respect to CP-specific the role of CP-specific in electrical signalling, excitation contraction coupling, and excretion will be unravelled. The evolution of electrical activity and carnivory of plants is worth being examined not only for its importance in general, but also as a model for understanding the evolution of the human nervous and endocrine system.

2 481 057 €

Start date: 2010-03-01, End date: 2015-02-28

Dikes and sills are large sheet-like intrusions transporting and storing magma in the Earth’s crust. When propagating, they generate seismicity and deformation and may lead to volcanic eruption. The physics of magma-filled structures is similar to that of any fluid-filled reservoir, such as oil fields and CO2 reservoirs created by sequestration. This project aims to address old and new unresolved challenging questions related to dike propagation, sill emplacement and in general to the dynamics of fluid and gas-filled reservoirs. I propose to focus on crustal deformation, induced seismicity and external stress fields to study the signals dikes and sills produce, how they grow and why they reactivate after years of non-detected activity. I will combine experimental, numerical and analytical techniques, in close cooperation with volcano observatories providing us with the data necessary to validate our models. In the lab, I will simulate magma propagation injecting fluid into solidified gelatin. I will also contribute to a project, currently under evaluation, on the monitoring of a CO2 sequestration site. At the same time, I will address theoretical aspects, extending static models to dynamic cases and eventually developing a comprehensive picture of the multi faceted interaction between external stress field, magma and rock properties, crustal deformation and seismicity. I also plan, besides presenting my team’s work in the major national and international geophysical conferences, to produce, with technical support from the media services of DKRZ (Deutsches Klimarechenzentrum), an audiovisual teaching DVD illustrating scientific advances and unresolved issues in magma dynamics, in the prediction of eruptive activity and in the physics of reservoirs.

1 507 679 €

Start date: 2010-07-01, End date: 2015-06-30

Vitamin A supplementation (VAS) and vaccines are the most powerful tools to reduce child mortality in low-income countries. However, we may not use these interventions optimally because we disregard that the interventions may have immunomodulatory effects which differ for boys and girls and which may interact with the effects of other interventions. I have proposed the hypothesis that VAS and vaccines interact. This hypothesis is supported by randomised and observational studies showing that the combination of VAS and DTP may be harmful. I have furthermore proposed that VAS has sex-differential effects. VAS seems beneficial for boys but may not carry any benefits for girls. These findings challenge the current understanding that VAS and vaccines have only targeted effects and can be given together without considering interactions. This is of outmost importance for policy makers. The global trend is to combine health interventions for logistic reasons. My research suggests that this may not always be a good idea. Furthermore, the concept of sex-differential response to our common health interventions opens up for a completely new understanding of the immunology of the two sexes and may imply that we need to treat the two sexes differently in order to treat them optimally possibly also in high-income countries. In the present proposal I outline a series of inter-disciplinary epidemiological and immunological studies, which will serve to determine the overall and sex-differential effects of VAS and vaccines, the mechanisms behind these effects, and the basis for the immunological difference between boys and girls. If my hypotheses are true we can use the existing tools in a more optimal way to reduce child mortality without increasing costs. Thus, the results could lead to shifts in policy as well as paradigms.

1 686 043 €

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