ERC FUNDED PROJECTS

Nature has evolved ultimate chemical functions based on controlling and altering conformation of its molecular machinery. Prominent examples include enzyme catalysis and information storage/duplication in nucleic acids. These achievements are based on large and complex yet remarkably defined structures obtained through folding of polymeric chains and a subtle interplay of non-covalent forces. Nature uses a limited set of building blocks – e.g. twenty amino-acids and four nucleobases – with specific abilities to impart well-defined folds. In the last decade, chemists have discovered foldamers: non-natural oligomers and polymers also prone to adopt folded structures. The emergence of foldamers has far reaching implications. A new major long term prospect is open to chemistry: the de novo synthesis of artificial objects resembling biopolymers in terms of their size, complexity, and efficiency at achieving defined functions, yet having chemical structures beyond the reach of biopolymers amenable to new properties and functions. The PI of this project has shown internationally recognized leadership in the development of a class of foldamers, aromatic oligoamides, whose features arguably make them the most suitable candidates to systematically explore what folded structures beyond biopolymers give access to. This project aims at developing methods to allow the routine fabrication of 20-40 units long aromatic oligoamide foldamers (6-15 kDa) designed to fold into artificial molecular containers having engineerable cavities and surfaces for molecular recognition of organic substrates, in particular large peptides and saccharides, polymers, and proteins. The methodology rests on modelling based design, multistep organic synthesis of heterocyclic monomers and their assembly into long sequences, structural elucidation using, among other techniques, x-ray crystallography, and the physico-chemical characterization of molecular recognition events.

2 496 216 €

Start date: 2013-06-01, End date: 2018-05-31

The numerical simulation of complex compressible flow problem is still a challenge nowaday even for simple models. In our opinion, the most important hard points that need currently to be tackled and solved is how to obtain stable, scalable, very accurate, easy to code and to maintain schemes on complex geometries. The method should easily handle mesh refinement, even near the boundary where the most interesting engineering quantities have to be evaluated. Unsteady uncertainties in the model, for example in the geometry or the boundary conditions should represented efficiently.This proposal goal is to design, develop and evaluate solutions to each of the above problems. Our work program will lead to significant breakthroughs for flow simulations. More specifically, we propose to work on 3 connected problems: 1-A class of very high order numerical schemes able to easily deal with the geometry of boundaries and still can solve steep problems. The geometry is generally defined by CAD tools. The output is used to generate a mesh which is then used by the scheme. Hence, any mesh refinement process is disconnected from the CAD, a situation that prevents the spread of mesh adaptation techniques in industry! 2-A class of very high order numerical schemes which can utilize possibly solution dependant basis functions in order to lower the number of degrees of freedom, for example to compute accurately boundary layers with low resolutions. 3-A general non intrusive technique for handling uncertainties in order to deal with irregular probability density functions (pdf) and also to handle pdf that may evolve in time, for example thanks to an optimisation loop. The curse of dimensionality will be dealt thanks Harten's multiresolution method combined with sparse grid methods. Currently, and up to our knowledge, no scheme has each of these properties. This research program will have an impact on numerical schemes and industrial applications.

1 432 769 €

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

This project focuses on one of the most fascinating events of the long history of the human species: the origins and spread of agriculture. Research over the past 40 years has provided an invaluable dataset on crop domestication and the spread of agriculture into Europe. However, despite the enormous advances in research there are important areas that remain almost unexplored, some of immense interest. This is the case of the western Mediterranean region from where our knowledge is still limited (Iberian Peninsula) or almost inexistent (northern Morocco). The last few years have witnessed a considerable increase in archaeobotany and the effort of a group of Spanish researchers working together in different aspects of agriculture has started to produce the first results. My proposal will approach the study of the arrival of agriculture to the western Mediterranean by exploring different interrelated research areas. The project involves the application of different techniques (analysis of charred plant remains, pollen and non-pollen microfossils, phytoliths, micro-wear analyses, isotopes, soil micromorphology, genetics, and ethnoarchaeology) which will help to define the emergence and spread of agriculture in the area, its likely place of origin, its main technological attributes as well as the range crop husbandry practices carried out. The interaction between the different approaches and the methodologies involved will allow achieving a greater understanding of the type of agriculture that characterized the first farming communities in the most south-western part of Europe.

1 545 169 €

Start date: 2009-04-01, End date: 2013-03-31

This project focuses on two questions about host/parasite interactions: how do biotrophic plant pathogens suppress host defence? and, what is the basis for pathogen specialization on specific host species? A broadly accepted model explains resistance and susceptibility to plant pathogens. First, pathogens make conserved molecules ( PAMPS ) such as flagellin, that plants detect via cell surface receptors, leading to PAMP-Triggered Immunity (PTI). Second, pathogens make effectors that suppress PTI. Third, plants carry 100s of Resistance (R) genes that detect an effector, and activate Effector-Triggered Immunity (ETI). One effector is sufficient to trigger resistance. Albugo candida (Ac) (white rust) strongly suppresses host defence; Ac-infected Arabidopsis are susceptible to pathogen races to which they are otherwise resistant. Ac is an oomycete, not a fungus. Arabidopsis is resistant to races of Ac that infect brassicas. The proposed project involves three programs. First ( genomics, transcriptomics and bioinformatics ), we will use next-generation sequencing (NGS) methods (Solexa and GS-Flex), and novel transcriptomics methods to define the genome sequence and effector set of three Ac strains, as well as carrying out >40- deep resequencing of 7 additional Ac strains. Second, ( effectoromics ), we will carry out functional assays using Effector Detector Vectors (Sohn Plant Cell 19:4077 [2007]), with the set of Ac effectors, screening for enhanced virulence, for suppression of defence, for effectors that are recognized by R genes in disease resistant Arabidopsis and for host effector targets. Third, ( resistance diversity ), we will characterize Arabidopsis germplasm for R genes to Ac, both for recognition of Arabidopsis strains of Ac, and for recognition in Arabidopsis of effectors from Ac strains that infect brassica. This proposal focuses on Ac, but will establish methods that could discover new R genes in non-hosts against many plant diseases.

2 498 923 €

Start date: 2009-01-01, End date: 2014-06-30

The aim of this proposal is to understand a novel regulatory signaling network controlling insulin secretion, fat accumulation and energy balance centered around selected components of the TGF-² signaling system, including Activins A and B, GDF-3 and their receptors ALK7 and ALK4. Recent results from my laboratory indicate that these molecules are part of paracrine signaling networks that control important functions in pancreatic islets and adipose tissue through feedback inhibition and feed-forward regulation. These discoveries have open up a new research area with important implications for the understanding of metabolic networks and the treatment of human metabolic syndromes, such as diabetes and obesity. To drive progress in this new research area beyond the state-of-the-art it is proposed to: i) Elucidate the molecular mechanisms by which Activins regulate Ca2+ influx and insulin secretion in pancreatic ²-cells; ii) Elucidate the molecular mechanisms underlying the effects of GDF-3 on adipocyte metabolism, turnover and fat accumulation; iii) Investigate the interplay between insulin levels and fat deposition in the development of insulin resistance using mutant mice lacking Activin B and GDF-3; iv) Investigate tissue-specific contributions of ALK7 and ALK4 signaling to metabolic control by generating and characterizing conditional mutant mice; v) Investigate the effects of specific and reversible inactivation of ALK7 and ALK4 on metabolic regulation using a novel chemical-genetic approach based on analog-sensitive alleles. This is research of a high-gain/high-risk nature. It is posed to open unique opportunities for further exploration of complex metabolic networks. The development of drugs capable of enhancing insulin secretion, limiting fat accumulation and ameliorating diet-induced obesity by targeting components of the ALK7 signaling network will find a strong rationale in the results of the proposed work.

2 462 154 €

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

Attosecond light pulses are generated when an intense laser interacts with a gas target. These pulses are not only short, enabling the study of electronic processes at their natural time scale, but also coherent. The vision of this proposal is to extend temporal coherent control concepts to a completely new regime of time and energy, combining (i) ultrashort pulses (ii) broadband excitation (iii) high photon energy, allowing scientists to reach not only valence but also inner shells in atoms and molecules, and, when needed, (iv) high spatial resolution. We want to explore how elementary electronic processes in atoms, molecules and more complex systems can be controlled by using well designed sequences of attosecond pulses. The research project proposed is organized into four parts: 1. Attosecond control of light leading to controlled sequences of attosecond pulses We will develop techniques to generate sequences of attosecond pulses with a variable number of pulses and controlled carrier-envelope-phase variation between consecutive pulses. 2. Attosecond control of electronic processes in atoms and molecules We will investigate the dynamics and coherence of phenomena induced by attosecond excitation of electron wave packets in various systems and we will explore how they can be controlled by a controlled sequence of ultrashort pulses. 3. Intense attosecond sources to reach the nonlinear regime We will optimize attosecond light sources in a systematic way, including amplification of the radiation by injecting a free electron laser. This will open up the possibility to develop nonlinear measurement and control schemes. 4. Attosecond control in more complex systems, including high spatial resolution We will develop ultrafast microscopy techniques, in order to obtain meaningful temporal information in surface and solid state physics. Two directions will be explored, digital in line microscopic holography and photoemission electron microscopy.

2 250 000 €

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

This four-year interdisciplinary project addresses the question what has been learned through the use of better regulation ? Better regulation is a flagship policy on the Lisbon agenda for growth and jobs. Its aims are to provide new governance architectures for law-making, to increase the competitiveness of the regulatory environment, and to secure wide social legitimacy for multi-level systems of rules. Whilst most of the research has looked at how better regulation is changing, this project will produce findings on what has changed because of better regulation. Theoretically, the project will use (and significantly improve on) theories of policy learning. Empirically, it will cover Denmark, Italy, the Netherlands, Poland, the UK and the EU including multi-level analysis and analysis by sector of regulation. Methodologically, the project will draw on comparative analysis of types of learning, experiments with regulatory policy-makers in six countries and the European Commission, large-n analysis of impact assessments, backward-mapping of legislation (to appraise the role played by better regulation in the formulation or laws in the UK and the EU), meta-analysis of case-studies and co-production of knowledge with better regulation officers. Dissemination will target both stakeholders (i.e., policy officers, civil society organizations, and business federations) and academic conferences in political science, law, and risk analysis, with a major research monograph to be completed in year 4 and a final interdisciplinary conference.

948 448 €

Start date: 2009-09-01, End date: 2013-09-30

Applied mathematics is concerned with developing models with predictive capability, and with probing those models to obtain qualitative and quantitative insight into the phenomena being modelled. Statistics is data-driven and is aimed at the development of methodologies to optimize the information derived from data. The increasing complexity of phenomena that scientists and engineers wish to model, together with our increased ability to gather, store and interrogate data, mean that the subjects of applied mathematics and statistics are increasingly required to work in conjunction. This research proposal is concerned with a research program at the interface between these two disciplines, aimed at problems in differential equations where profusion of data and the sophisticated model combine to produce the mathematical problem of obtaining information from a probability measure on function space. Applications are far-reaching and include the atmospheric sciences, geophysics, chemistry, econometrics and signal processing. The objectives of the research are: (i) to create the systematic foundations for a range of problems at the applied mathematics and statistics interface which share the common mathematical structure underpinning the range of applications described above; (ii) to exploit this common mathematical structure to design effecient algorithms to sample probability measures on function space; (iii) to apply these algorithms to attack a range of significant problems arising in molecular dynamics and in the atmospheric sciences.

1 693 501 €

Start date: 2008-12-01, End date: 2014-11-30

Despite the discovery of amyloidosis more than a century ago, the molecular and cellular mechanisms of these devastating human disorders remain obscure. In addition to their involvement in disease, amyloid fibrils perform physiological functions, whilst others have potentials as biomaterials. To realise their use in nanotechnology and to enable the development of amyloid therapies, there is an urgent need to understand the molecular pathways of amyloid assembly and to determine how amyloid fibrils interact with cells and cellular components. The challenges lie in the transient nature and low population of aggregating species and the panoply of amyloid fibril structures. This molecular complexity renders identification of the culprits of amyloid disease impossible to achieve using traditional methods. Here I propose a series of exciting experiments that aim to cast new light on the molecular and cellular mechanisms of amyloidosis by exploiting approaches capable of imaging individual protein molecules or single protein fibrils in vitro and in living cells. The proposal builds on new data from our laboratory that have shown that amyloid fibrils (disease-associated, functional and created from de novo designed sequences) kill cells by a mechanism that depends on fibril length and on cellular uptake. Specifically, I will (i) use single molecule fluorescence and non-covalent mass spectrometry and to determine why short fibril samples disrupt biological membranes more than their longer counterparts and electron tomography to determine, for the first time, the structural properties of cytotoxic fibril ends; (ii) develop single molecule force spectroscopy to probe the interactions between amyloid precursors, fibrils and cellular membranes; and (iii) develop cell biological assays to discover the biological mechanism(s) of amyloid-induced cell death and high resolution imaging and electron tomography to visualise amyloid fibrils in the act of killing living cells.

2 498 465 €

Start date: 2013-05-01, End date: 2019-04-30

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

Despite improved therapy, cardiovascular diseases remain the most prevalent diseases in the European Union and the incidence is rising due to increased obesity and ageing. The fine-tuned regulation of vascular functions is essential not only for preventing atherosclerotic diseases, but also after tissue injury, where the coordinated growth and maturation of new blood vessels provides oxygen and nutrient supply. On the other hand, excessive vessel growth or the generation of immature, leaky vessels contributes to pathological angiogenesis. Thus, the regulation of the complex processes governing vessel growth and maturation has broad impacts for several diseases ranging from tumor angiogenesis, diabetic retinopathy, to ischemic cardiovascular diseases. MicroRNAs (miRs) are small noncoding RNAs, which play a crucial role in embryonic development and tissue homeostasis. However, only limited information is available regarding the role of miRs in the vasculature. MiRs regulate gene expression by binding to the target mRNA leading either to degradation or to translational repression. Because miRs control patterns of target genes, miRs represent an attractive and promising therapeutic target to interfere with complex processes such as neovascularization and repair of ischemic tissues. Therefore, the present application aims to identify miRs in the vasculature, which regulate vessel growth and vessel remodelling and may, thus, serve as therapeutic targets in ischemic diseases. Since ageing critically impairs endothelial function, neovascularization and vascular repair, we will specifically identify miRs, which are dysregulated during ageing in endothelial cells and pro-angiogenic progenitor cells, in order to develop novel strategies to rescue age-induced impairment of neovascularization. Beyond the specific scope of the present application, the principle findings may have impact for other diseases, where deregulated vessel growth causes or accelerates disease states.

2 375 394 €

Start date: 2009-03-01, End date: 2014-02-28

Isoperimetric and Sobolev inequalities are the best known examples of geometric-functional inequalities. In recent years the PI and collaborators have obtained new and sharp quantitative versions of these and other important related inequalities. These results have been obtained by the combined use of classical symmetrization methods, new tools coming from mass transportation theory, deep geometric measure tools and ad hoc symmetrizations. The objective of this project is to further develop thes techniques in order to get: sharp quantitative versions of Faber-Krahn inequality, Gaussian isoperimetric inequality, Brunn-Minkowski inequality, Poincaré and Sobolev logarithm inequalities; sharp decay rates for the quantitative Sobolev inequalities and Polya-Szegö inequality.

600 000 €

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

T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory. I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.

2 500 000 €

Start date: 2013-08-01, End date: 2018-07-31

Our research interests lie in breaking new ground in studying mechanism-based functions of AP-1 (Fos/Jun) in vivo with the aim of obtaining a more global perspective on AP-1 in human physiology and disease/cancer. The unresolved issues regarding the AP-1 subunit composition will be tackled biochemically and genetically in various cell types including bone, liver and skin, the primary organs affected by altered AP-1 activity. I plan to utilize the knowledge gained on AP-1 functions in the mouse and transfer it to human disease. The opportunities here lie in exploiting the knowledge of AP-1 target genes and utilizing this information to interfere with pathways involved in normal physiology and disease/cancer. The past investigations revealed that the functions of AP-1 are an essential node at the crossroads between life and death in different cellular systems. I plan to further exploit our findings and concentrate on utilising better mouse models to define these connections. The emphasis will be on identifying molecular signatures and potential treatments in models for cancer, inflammatory and fibrotic diseases. Exploring genetically modified stem cell-based therapies in murine and human cells is an ongoing challenge I would like to meet in the forthcoming years at the CNIO. In addition, the mouse models will be used for mechanism-driven therapeutic strategies and these studies will be undertaken in collaboration with the Experimental Therapeutics Division and the service units such as the tumor bank. The project proposal is divided into 6 Goals (see also Figure 1): Some are a logical continuation based on previous work with completely new aspects (Goal 1-2), some focussing on in depth molecular analyses of disease models with innovative and unconventional concepts, such as for inflammation and cancer, psoriasis and fibrosis (Goal 3-5). A final section is devoted to mouse and human ES cells and their impact for regenerative medicine in bone diseases and cancer.

2 500 000 €

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

The proposed project aims to create a center of excellence that aims at understanding the approximability of NP-hard optimization problems. In particular, for central problems like vertex cover, coloring of graphs, and various constraint satisfaction problems we want to study upper and lower bounds on how well they can be approximated in polynomial time. Many existing strong results are based on what is known as the Unique Games Conjecture (UGC) and a significant part of the project will be devoted to studying this conjecture. We expect that a major step needed to be taken in this process is to further develop the understanding of Boolean functions on the Boolean hypercube. We anticipate that the tools needed for this will come in the form of harmonic analysis which in its turn will rely on the corresponding results in the analysis of functions over the domain of real numbers.

2 376 000 €

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

The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.

2 422 271 €

Start date: 2013-05-01, End date: 2019-04-30

"Following the advent of graphene with its wide range of unique properties, several other one-atom-thick crystals have been isolated and their preliminary studies have been undertaken. They range from semiconducting monolayers of MoS2 and NbSe2, which similar to graphene exhibit the electric field effect and relatively high electronic quality, to wide-gap insulators such as boron-nitride monolayers that can serve as atomically-thin tunnel barriers. This library of two-dimensional crystals opens a possibility to construct various 3D structures with on-demand properties, which do not exist in nature but can be assembled in Lego style by stacking individual atomic planes on top of each other in a desired sequence. This project is to explore this new avenue. We will design, fabricate and study multilayer materials ranging from basic heterostructures that consist of a few alternating layers of graphene and boron nitride and already exhibit a rich spectrum of new phenomena, as recently demonstrated by the applicant’s group, to complex artificial materials containing many layers of different 2D crystals and mimicking, for example, layered superconductors. In a similar manner, various electronic, optoelectronic, micromechanical and other devices will be developed and investigated. The applicant’s aim is to search for new materials with unique properties, novel devices with better characteristics and new physics that is likely to emerge along the way. The proposed research offers many exciting opportunities and can lead to the development of a large unexplored field with impact exceeding even that of graphene research. This presents a unique, once-in-decade, opportunity to make a very significant breakthrough in condensed matter physics and materials science."

2 200 000 €

Start date: 2013-05-01, End date: 2018-04-30

Magnetic fields in stars, planets, accretion discs, and galaxies are believed to be the result of a dynamo process converting kinetic energy into magnetic energy. This work focuses on the solar dynamo, but dynamos in other astrophysical systems will also be addressed. In particular, direct high-resolution three-dimensional simulations are used to understand particular aspects of the solar dynamo and ultimately to simulate the solar dynamo as a whole. Phenomenological approaches will be avoided in favor of obtaining rigorous results. A major problem is catastrophic quenching, i.e. the decline of dynamo effects in inverse proportion to the magnetic Reynolds number, which is huge. Tremendous advances have been made in the last few years since the cause of catastrophic quenching in dynamos has been understood in terms of magnetic helicity evolution. The numerical tools are now in place to allow for magnetic helicity fluxes via coronal mass ejections, thus alleviating catastrophic quenching. This work employs simulations in spherical shells, augmented by Cartesian simulations in special cases. The roles of the near-surface shear layer, the tachocline, as well as pumping in the bulk of the convection zone are to be clarified. The Pencil Code will be used for most applications. The code is third order in time and sixth order in space and is used for solving the hydromagnetic equations. It is a public domain code developed by roughly 20 scientists world wide and maintained under an a central versioning system at Nordita. Automatic nightly tests of currently 30 applications ensure the integrity of the code. It is used for a wide range of applications and may include the effects of radiation, self-gravity, dust, chemistry, variable ionization, cosmic rays, in addition to those of magnetohydrodynamics. The code with its infrastructure offers a good opportunity for individuals within a broad group of people to develop new tools that may automatically be useful to others.

2 220 000 €

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

Atmospheric aerosol particles and trace gases affect the quality of our life in many ways (e.g. health effects, changes in climate and hydrological cycle). Trace gases and atmospheric aerosols are tightly connected via physical, chemical, meteorological and biological processes occurring in the atmosphere and at the atmosphere-biosphere interface. One important phenomenon is atmospheric aerosol formation, which involves the production of nanometer-size particles by nucleation and their growth to detectable sizes. The main scientific objectives of this project are 1) to quantify the mechanisms responsible for atmospheric new particle formation and 2) to find out how important this process is for the behaviour of the global aerosol system and, ultimately, for the whole climate system. Our scientific plan is designed as a research chain that aims to advance our understanding of climate and air quality through a series of connected activities. We start from molecular simulations and laboratory measurements to understand nucleation and aerosol thermodynamic processes. We measure nanoparticles and atmospheric clusters at 15-20 sites all around the world using state of the art instrumentation and study feedbacks and interactions between climate and biosphere. With these atmospheric boundary layer studies we form a link to regional-scale processes and further to global-scale phenomena. In order to be able to simulate global climate and air quality, the most recent progress on this chain of processes must be compiled, integrated and implemented in Climate Change and Air Quality numerical models via novel parameterizations.

2 000 000 €

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

The overarching research question of this project is: how is authoritarian rule affected by and responding to globalisation of (a) information and communication, (b) association, and (c) people movement? The wholly unpredicted series of revolts that recently spread across the Arab world suggests that the nature and sustainability of contemporary authoritarian rule are not well-understood. Openness to global ICT and media, international NGOs, and inflow and outflow of people have thrown up new challenges for authoritarian rulers in terms of how to control citizens. This project investigates changes in both the nature and the sustainability of authoritarian rule in relation to the erosion of decision-making autonomy at the state level posited by globalisation theorists. In four sub-projects, this project will investigate: 1. Whether, how and to what extent globalisation of information and communication, association, and people movement affect authoritarian persistence (longitudinal quantitative study, 1970-2011) 2. How, i.e. with what policy mechanisms, authoritarian states respond to globalisation of information and communication, association, and people movement (qualitative multi-sited studies relating to Belarus, China, Iran and Zimbabwe) 3. How to understand the phenomenon of subnational authoritarianism in its engagement with the democratic state and the wider world in relation to information and communication, association, and people movement (mixed method subnational studies of states within India and Mexico) 4. What authoritarianism is in a global age: reconsidering authoritarianism’s defining characteristics of low accountability and high coercion, and whether these still relate exclusively to statehood (theory study) The project will transcend the theoretical and empirical separation between globalisation studies (which have neglected authoritarian contexts) and authoritarianism studies(which have taken relatively little notice of effects of globalisation)

2 451 179 €

Start date: 2013-10-01, End date: 2019-02-28

Neurons make long-distance connections with synaptic targets via axons. These axons survive throughout the lifetime of an organism, often many years in mammals, yet how axons are maintained is not fully understood. Recently, we provided in vivo evidence that local mRNA translation in mature axons is required for their maintenance. This new finding, along with in vitro work from other groups, indicates that promoting axonal protein synthesis is a key mechanism by which trophic factors act to prevent axon degeneration. Here we propose a program of research to investigate the importance of ribosomal proteins (RPs) in axon maintenance and degeneration. The rationale for this is fourfold. First, recent genome-wide studies of axonal transcriptomes have revealed that protein synthesis (including RP mRNAs) is the highest functional category in several neuronal types. Second, some RPs have evolved extra-ribosomal functions that include signalling, such as 67LR which acts both as a cell surface receptor for laminin and as a RP. Third, mutations in different RPs in vertebrates cause unexpectedly specific defects, such as the loss of optic axons. Fourth, preliminary results show that RP mRNAs are translated in optic axons in response to trophic factors. Collectively these findings lead us to propose that locally synthesized RPs play a role in axon maintenance through either ribosomal or extra-ribosomal function. To pursue this proposal, we will perform unbiased screens and functional assays using an array of experimental approaches and animal models. By gaining an understanding of how local RP synthesis contributes to axon survival, our studies have the potential to provide novel insights into how components conventionally associated with a housekeeping role (translation) are linked to axon degeneration. Our findings could provide new directions for developing therapeutic tools for neurodegenerative disorders and may have an impact on more diverse areas of biology and disease.

2 426 573 €

Start date: 2013-03-01, End date: 2018-09-30

NK cells that are well known by their ability to recognize and eliminate virus infected and tumor cells were also implicated in the defence against bacteria. However, the recognition of bacteria by NK cells is only poorly understood. we do not know how bacteria are recognized and the functional consequences of such recognition are also weakly understood. In the current proposal we aimed at determining the “NK cell receptor-bacterial interactome”. We will examine the hypothesis that NK inhibitory and activating receptors are directly involved in bacterial recognition. This ground breaking hypothesis is based on our preliminary results in which we show that several NK cell receptors directly recognize various bacterial strains as well as on a few other publications. We will generate various mice knockouts for NCR1 (a major NK killer receptor) and determine their microbiota to understand the physiological function of NCR1 and whether certain bacterial strains affects its activity. We will use different human and mouse NK killer and inhibitory receptors fused to IgG1 to pull-down bacteria from saliva and fecal samples and then use 16S rRNA analysis and next generation sequencing to determine the nature of the bacteria species isolated. We will identify the bacterial ligands that are recognized by the relevant NK cell receptors, using bacterial random transposon insertion mutagenesis approach. We will end this research with functional assays. In the wake of the emerging threat of bacterial drug resistance and the involvement of bacteria in the pathogenesis of many different chronic diseases and in shaping the immune response, the completion of this study will open a new field of research; the direct recognition of bacteria by NK cell receptors.

2 499 800 €

Start date: 2013-03-01, End date: 2018-02-28

The majority of the globe's population carries a mobile phone, but with the increasing proliferation of smart phones and tablet-computers the tele-traffic is predicted to grow 1000-fold over the next decade, especially, when aiming for creating the impression of ubiquitous and flawless 'tele-presence' based on crisp, three-dimensional (3D) video with its sense of joy and wonder. For tele-presence to become a reality requires a further quantum-leap from the popular 3G/4G smart phones and tablet-computers. This project will create the link-level enabling techniques of this transformational quantum leap to immersive Giga-bit 3D video communications, relying on Optical Wireless (OW) hotspots and their ad hoc networking. As a result, the Beam-Me-Up project will contribute to job- and wealth-creation in numeorus ways, as exemplified by the often-quoted economic benefits of 3G/4G phones on businesses. From an environmental perspective, flawless tele-presence has the potential of eliminating millions of flights/trips and hence will considerably reduce CO2 emissions, whilst reducing the related business-costs as well as saving precious time for the work-force. However, the transfiguration of the voice-only phone into today's intelligent smart phone was facilitated by a 1000-fold transmission-rate increase, which would result in a proportionally increased power consumption, CO2 emissions and in a soaring energy-bill. Tele-presence based on crisp Avatar-style 3D video has even higher bitrates and energy consumption. These radically new high-rate 3D tele-presence services can no longer be accommodated in the severely congested Radio Frequency (RF) band. Hence the project will create a suite of new OW system components, operating in the visible-light domain and will conceive low-power, low-complexity OW solutions to enable immersive Giga-bit 3D wireless video communications over heterogeneous networks.

2 470 416 €

Start date: 2013-03-01, End date: 2018-02-28

"We aim to establish a world-leading research capability in Europe for advancing novel models of asynchronous computation based upon principles inspired by brain function. This work will accelerate progress towards an understanding of how the potential of brain-inspired many-core architectures may be harnessed. The results will include new brain-inspired models of asynchronous computation and new brain- inspired approaches to fault-tolerance and reliability in complex computer systems. Many-core processors are now established as the way forward for computing from embedded systems to supercomputers. An emerging problem with leading-edge silicon technology is a reduction in the yield and reliability of modern processors due to high variability in the manufacture of the components and interconnect as transistor geometries shrink towards atomic scales. We are faced with the longstanding problem of how to make use of a potentially large array of parallel processors, but with the new constraint that the individual elements are the system are inherently unreliable. The human brain remains as one of the great frontiers of science – how does this organ upon which we all depend so critically actually do its job? A great deal is known about the underlying technology – the neuron – and we can observe large-scale brain activity through techniques such as magnetic resonance imaging, but this knowledge barely starts to tell us how the brain works. Something is happening at the intermediate levels of processing that we have yet to begin to understand, but the essence of the brain's massively-parallel information processing capabilities and robustness to component failure lies in these intermediate levels. These two issues draws us towards two high-level research questions: • Can our growing understanding of brain function point the way to more efficient parallel, fault-tolerant computing? • Can massively parallel computing resources accelerate our understanding of brain function"

2 399 761 €

Start date: 2013-03-01, End date: 2018-02-28