ERC FUNDED PROJECTS

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

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 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

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

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

While heparin, a glacosaminoglycan (GAG) has served as an anticoagulant for more than 60 years, the structure-activity relationship of heparin and chondroitin sulfate for specific interactions with proteins are still poorly understood. It has become evident that defined lengths and sequences or patterns are responsible for binding to a particular protein and modulating its biological activity. Determination of the structure-activity relationships of heparins and chondroitins creates an opportunity to modulate processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. The isolation of pure GAGs is extremely tedious and chemical synthesis is often the only means to access defined oligosaccharides. Currently available synthetic methods for the preparation of heparins and chondroitins are time consuming and lack generality. Therefore, it is still impossible to create large collections of GAG oligosaccharides for systematic studies of GAG-protein interactions. The overall goal of the project is the development of all aspects of automated GAG synthesis, the procurement of a large collection of heparin and chondroitin oligosaccharides of 2-10 sugars in length with a linker for ready attachment to microarray surfaces and other tools. These molecular tools will be employed to study the interaction of GAGs with growth factors, chemokines and other proteins. The specific aims include: 1) Synthesis of uronic acid and galactosamine building blocks; 2) Development of a new linker for automated GAG solid phase synthesis; 3) Construction of a new automated oligosaccharide synthesizer; 4) Development of methods for the automated assembly of heparin and chondroitin sulfate oligosaccharides; 5) Synthesis of a collection of defined heparin and chondroitin sulfate oligosaccharides; 6) Construction of synthetic GAG microarrays and SPR; 7) Preparation of GAG dendrimers and quantum dots.

2 500 000 €

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