ERC FUNDED PROJECTS

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

This proposal wishes to fundamentally improve our understanding of the role of tropical freshwater ecosystems in carbon (C) cycling on the catchment scale. It uses an unprecedented combination of state-of-the-art proxies such as stable isotope, 14C and biomarker signatures to characterize organic matter, radiogenic isotope signatures to determine particle residence times, as well as field measurements of relevant biogeochemical processes. We focus on tropical systems since there is a striking lack of data on such systems, even though riverine C transport is thought to be disproportionately high in tropical areas. Furthermore, the presence of landscape-scale contrasts in vegetation (in particular, C3 vs. C4 plants) are an important asset in the use of stable isotopes as natural tracers of C cycling processes on this scale. Freshwater ecosystems are an important component in the global C cycle, and the primary link between terrestrial and marine ecosystems. Recent estimates indicate that ~2 Pg C y-1 (Pg=Petagram) enter freshwater systems, i.e., about twice the estimated global terrestrial C sink. More than half of this is thought to be remineralized before it reaches the coastal zone, and for the Amazon basin this has even been suggested to be ~90% of the lateral C inputs. The question how general these patterns are is a matter of debate, and assessing the mechanisms determining the degree of processing versus transport of organic carbon in lakes and river systems is critical to further constrain their role in the global C cycle. This proposal provides an interdisciplinary approach to describe and quantify catchment-scale C transport and cycling in tropical river basins. Besides conceptual and methodological advances, and a significant expansion of our dataset on C processes in such systems, new data gathered in this project are likely to provide exciting and novel hypotheses on the functioning of freshwater systems and their linkage to the terrestrial C budget.

1 745 262 €

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

In this project, innovative techniques to reconstruct ancient economies are developed and new insights in the trade and processing of mineral raw materials are gained based on interdisciplinary archaeological and archaeometrical research. An innovative methodology for and a practical provenance database of the primary origin of natron glass from the Hellenistic-Roman world will be established. The project investigates both production and consumer sites of glass raw materials using both typo-chronological and archaeometrical (isotope geochemical) study of finished glass artefacts at consumer sites as well as mineralogical and chemical characterisation of raw glass and mineral resources at primary production sites. Suitable sand resources in the locations described by ancient authors will be identified through geological prospecting on the basis of literature review and field work. Sand and flux (natron) deposits will be mineralogically and geochemically characterised and compared to the results of the archaeological and geochemical investigations of the glass. Through integrated typo-chronological and archaeometrical analysis, the possible occurrence of primary production centres of raw glass outside the known locations in Syro-Palestine and Egypt, particularly in North-Africa, Italy, Spain and Gaul will be critically studied. In this way, historical, archaeological and archaeometrical data are combined, developing new interdisciplinary techniques for innovative archaeological interpretation of glass trade in the Hellenistic-Roman world.

954 960 €

Start date: 2009-11-01, End date: 2014-10-31

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

Bioinorganic chemistry is a rapidly expanding area of research, but the potential for the therapeutic application of metal complexes is highly underdeveloped. The basic principles required to guide the development of metal-containing therapeutic agents are lacking, despite the unique therapeutic opportunities which they offer. It is the goal of the proposed research to establish basic principles of medicinal coordination chemistry of metals that will allow the rational screening of future metallopharmaceuticals. We propose to utilize the power of inorganic chemistry to provide new knowledge of and new approaches for intervention in biological systems. This will be based on improved understanding of reactions of metal complexes under physiological conditions, on improving the specificity of their interactions, and gaining control over the potential toxicity of synthetic metal complexes. The research programme is highly interdisciplinary involving chemistry, physics, biology and pharmacology, with potential for the discovery of truly novel medicines, especially for the treatment of diseases and conditions which are currently intractable, such as cancer. The challenging and ambitious goals of the present work involve transition metal complexes with novel chemical and biochemical mechanisms of action. They will contain novel features which allow them (i) to be selectively activated by light in cells, or (ii) to be activated by a structural transition, or (ii) exhibit catalytic activity in cells. This ground-breaking research potentially has a very high impact and is based on recent discoveries in the applicant s laboratory. A feature of the programme is the use of state-of-the-art-and-beyond methodology to advance knowledge of medicinal metal coordination chemistry.

1 565 397 €

Start date: 2010-07-01, End date: 2015-12-31

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

China s economy has expanded at breakneck speed to become the 3rd largest trading country in the world and the largest recipient of foreign direct investment (FDI). Entry into the WTO in 2001 was a landmark event in this ongoing process and I propose to study several channels through which it spurred China s industrial development. Crucially, I will take an integrated view of the different ways in which Chinese and Western firms interact: through trade flows, as suppliers or competitors, FDI, or knowledge transfers. First, I investigate the existence and magnitude of a causal link from the trade reforms to productivity growth. Second, I look for evidence of capability upgrading, such as increased production efficiency, an ability to produce higher quality products, or introduce new products by innovating. Third, I study the mechanisms for the impact of trade and FDI on local firms, in particular assessing the relative importance of increased market competition and the transfer of know-how from foreign firms. For this analysis, I draw heavily on a unique data set. Information on the universe of Chinese manufacturing firms is being linked to the universe of Chinese trade transactions. These are unique research tools on their own, but as a linked data set, the only comparable one in the world is for the U.S. economy. The Chinese data has the advantage to contain detailed information on FDI, distinguishes between ordinary and processing trade, and contains information on innovation, such as R&D and sales of new goods. Answering the above questions is important for other developing countries wanting to learn from China s experience and for Western firms assessing how quickly Chinese firms will become viable suppliers of sophisticated inputs or direct competitors. By estimating models that are explicitly derived from new theories, I advance the literature at the interaction of international and development economics, industrial organization, economic geography.

944 940 €

Start date: 2010-02-01, End date: 2016-01-31

Eukaryotic cells inherit much of their genomic information in the form of chromosomes during cell division. Centimetre-long DNA molecules are packed into micrometer-sized chromosomes to enable this process. How DNA is organised within mitotic chromosomes is still largely unknown. A key structural protein component of mitotic chromosomes, implicated in their compaction, is the condensin complex. In this proposal, we aim to elucidate the molecular architecture of mitotic chromosomes, taking advantage of new genomic techniques and the relatively simple genome organisation of yeast model systems. We will place particular emphasis on elucidating the contribution of the condensin complex, and the cell cycle regulation of its activities, in promoting chromosome condensation. Our previous work has provided genome-wide maps of condensin binding to budding and fission yeast chromosomes. We will continue to decipher the molecular determinants for condensin binding. To investigate how condensin mediates DNA compaction, we propose to generate chromosome-wide DNA/DNA proximity maps. Our approach will be an extension of the chromosome conformation capture (3C) technique. High throughput sequencing of interaction points has provided a first glimpse of the interactions that govern chromosome condensation. The role that condensin plays in promoting these interactions will be investigated. The contribution of condensin s ATP-dependent activities, and cell cycle-dependent post-translational modifications, will be studied. This will be complemented by mathematical modelling of the condensation process. In addition to chromosome condensation, condensin is required for resolution of sister chromatids in anaphase. We will develop an assay to study the catenation status of sister chromatids and how condensin may contribute to their topological resolution.

2 076 126 €

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

Diffusive shock acceleration is widely acknowledged as the most likely source of cosmic rays and high energy particles. The basic macroscopic theory of how cosmic rays gain energy during multiple shock crossings is well known, but the microphysics of the interaction between cosmic rays (CR) and the MHD background fluid remained poorly understood before the recent discovery of a new non-resonant instability by which the CR precursor could greatly amplify the ambient magnetic field. The aims of the project are: 1) to develop the first self-consistent non-linear simulation of the CR/MHD interaction; to calculate the magnitude of the saturated magnetic field and the maximum energy to which CR are accelerated. We will characterise the structure of the amplified magnetic field and compare it with x-ray observations of the time-evolving outer shock of supernova remnants (SNR). We will investigate the effect of various orientations of the shock relative to the ambient magnetic field, the effect of non-diffusive transport on the energy spectrum and CR escape from the SNR, and how these match observation. 2) to extend the simulation to relativistic shocks as found in gamma-ray bursts (GRB) and active galactic nuclei (AGN); to establish whether the non-resonant instability operates effectively at relativistic shock velocities, whether it explains the large magnetic field found in GRB, and determine the maximum CR energy achieved by relativistic shocks. 3) to investigate high density shocks in GRB, x-ray flashes (XRF) and supernovae (SN) where radiative processes, pair production and other particle/photon and particle/particle interactions are important. We shall investigate CR acceleration on SN shock breakout and very young SNR as a possible source of very high energy CR.

900 024 €

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