ERC FUNDED PROJECTS

This project proposes an analysis of the reconfigurations established in the socio-political vocabulary of the western Saharan region – southern Morocco, Western Sahara and Mauritania – from the “post-empire” to the contemporary period. The project should produce an analysis of 1) the social and political structures shared in the region, 2) the local variations of those structures, based on case studies, 3) their specific configurations, based on social markers such as gender, age, and class, 4) the use of those structures in different historical periods. All these will be under theoretical and ethnographic scrutiny in order to achieve its main goal: 5) to understand the recent articulation of the social and political structures of the Western Saharan region, with broader and often exogenous political vocabularies. The methodology used in this project is based on readings associated with different social sciences, with a particular focus on anthropology, history, and political science. The members of the research team, with experience and linguistic competence in the different geographies involved in this project, are expected to conduct original field enquiries, enabling a significant enhancement of the theoretical and ethnographic knowledge associated with this region. The project’s main goal is to analyse the types of interplay established between pre-modern socio-political traditions and contemporary political expression and activism, in a particularly sensitive – and academically disregarded – region. Its effort to integrate a context that is usually compartmentalized, as well as to put together a group of researchers generally “isolated” in their particular areas of expertise, geographies, or nations, should also be valued. The project’s results should enable the different contexts under study to be integrated into the wider maps of current scientific research, providing, at the same time a dissemination of its outputs to an extended audience.

1 192 144 €

Start date: 2017-04-01, End date: 2021-03-31

During the human lifetime 10000 trillion cell divisions take place to ensure tissue homeostasis and several vital functions in the organism. Mitosis is the process that ensures that dividing cells preserve the chromosome number of their progenitors, while deviation from this, a condition known as aneuploidy, represents the most common feature in human cancers. Here we will test two original concepts with strong implications for chromosome segregation fidelity. The first concept is based on the “tubulin code” hypothesis, which predicts that molecular motors “read” tubulin post-translational modifications on spindle microtubules. Our proof-of-concept experiments demonstrate that tubulin detyrosination works as a navigation system that guides chromosomes towards the cell equator. Thus, in addition to regulating the motors required for chromosome motion, the cell might regulate the tracks in which they move on. We will combine proteomic, super-resolution and live-cell microscopy, with in vitro reconstitutions, to perform a comprehensive survey of the tubulin code and the respective implications for motors involved in chromosome motion, mitotic spindle assembly and correction of kinetochore-microtubule attachments. The second concept is centered on the recently uncovered chromosome separation checkpoint mediated by a midzone-associated Aurora B gradient, which delays nuclear envelope reformation in response to incompletely separated chromosomes. We aim to identify Aurora B targets involved in the spatiotemporal regulation of the anaphase-telophase transition. We will establish powerful live-cell microscopy assays and a novel mammalian model system to dissect how this checkpoint allows the detection and correction of lagging/long chromosomes and DNA bridges that would otherwise contribute to genomic instability. Overall, this work will establish a paradigm shift in our understanding of how spatial information is conveyed to faithfully segregate chromosomes during mitosis.

2 323 468 €

Start date: 2016-07-01, End date: 2021-06-30

Interspecific competition is arguably the best interaction to address how individual trait variation and eco-evolutionary feedbacks shape species distributions and trait evolution, due to its indirect effects via the shared resource. However, a clear understanding of such feedbacks is only possible if each contributing factor can be manipulated independently. With COMPCON, we will address how individual variation, niche width, niche construction and the presence of competitors shape species distributions and trait evolution, using a system amenable to manipulation of all these variables. The system is composed of two spider mite species, Tetranychus urticae and T. ludeni, that up- and down-regulate plant defences (i.e., negative and positive niche construction, respectively). Tomato mutant plants with low defences will be used as an environment in which niche construction is not expressed. Furthermore, tomato plants will be grown under different cadmium concentrations, allowing quantitative variation of available niches. Using isogenic lines, we will measure individual variation in niche width, niche construction and competitive ability. Different combinations of lines will then be used to test key predictions of recent theory on how such variation affects coexistence with competitors. Subsequently, mite populations will evolve in environments with either one or more potential niches, in plants where niche construction is possible or not, and in presence or absence of competitors (coevolving or not). We will test how these selection pressures affect niche width, niche construction and competitive ability, as well as plant damage. Finally, we will re-derive isogenic lines from these treatments, to test how evolution under different scenarios affects individual variation in niche width. COMPCON will shed new light on the role of competition in shaping eco-evolutionary communities, with bearings on disciplines ranging from macro-ecology to evolutionary genetics

1 999 275 €

Start date: 2017-05-01, End date: 2022-04-30

Sugars, aminoacids or organic acids are typically solid at room temperature. Nonetheless when combined at a particular molar fraction they present a high melting point depression, becoming liquids at room temperature. These are called Natural Deep Eutectic Solvents – NADES. NADES are envisaged to play a major role on different chemical engineering processes in the future. Nonetheless, there is a significant lack of knowledge on fundamental and basic research on NADES, which is hindering their industrial applications. For this reason it is important to extend the knowledge on these systems, boosting their application development. NADES applications go beyond chemical or materials engineering and cover a wide range of fields from biocatalysis, extraction, electrochemistry, carbon dioxide capture or biomedical applications. Des.solve encompasses four major themes of research: 1 – Development of NADES and therapeutic deep eutectic solvents – THEDES; 2 – Characterization of the obtained mixtures and computer simulation of NADES/THEDES properties; 3 – Phase behaviour of binary/ternary systems NADES/THEDES + carbon dioxide and thermodynamic modelling 4 – Application development. Starting from the development of novel NADES/THEDES which, by different characterization techniques, will be deeply studied and characterized, the essential raw-materials will be produced for the subsequent research activities. The envisaged research involves modelling and molecular simulations. Des.solve will be deeply engaged in application development, particularly in extraction, biocatalysis and pharmaceutical/biomedical applications. The knowledge that will be created in this proposal is expected not only to have a major impact in the scientific community, but also in society, economy and industry.

1 877 006 €

Start date: 2017-03-01, End date: 2022-02-28

It has been recognized that growing cells within 3D structures reduces the gap between 2D in vitro cell cultures and native tissue physiology. This has been paving the way for the development of reliable 3D in vitro cell-based platforms with major impact in the reduction/elimination of animal experimentation, diseases modelling and drug development. So far, the many strategies that have been followed to bioengineer in vitro 3D human tissue models mostly rely on the random culture of cells within a 3D structure without reflecting the compositional and structural complexity of the native tissues. Recently proposed bioprinting technologies that allow accurate and high speed deposition of various cells and matrices at high resolution, have therefore great potential in the development of physiologically reliable 3D in vitro tissue models by recreating the different microenvironments/microfunctionalities found in each tissue. Nonetheless, among the components required for bioprinting, bioinks in particular have demanding requirements and much has still to be done regarding their intrinsic formulation to lead cell behaviour and support specific functionalities. ECM_INK intends to tackle this issue by developing cells-self extracellular matrices-based bioinks to create accurate and pathophysiological relevant 3D in vitro diseased skin tissue models. The development of cell phenotype-driven bioinks will generate complex microenvironments comprising varied cell types within matrices that were specifically designed to attain a particular response from each one of those cell types. The use of cells from patients suffering from chronic, genetic and neoplastic skin diseases represents a major advantage that will be reflected in the accuracy and functionality of the respective 3D in vitro models. The ultimate confirmation of their potential will be complete after validation using animal-free approaches reinforcing the intrinsic relationship of ECM_INK with the 3Rs policy.

1 998 939 €

Start date: 2017-05-01, End date: 2022-04-30

THE OBJECTIVE of this project is to explore the various ways in which the histories of the Balkan peoples were shared, connected and entangled, and in some cases became structurally inter-dependent in the course of the nineteenth and the twentieth centuries; also to explore transfers and crossings within the region and from Western Europe and Russia. What is offered is a provisional open-ended and long-term research program guided by a general paradigm , frame of reference and key concepts. I would rather keep the project open and flexible with regard to substantial issues, though with a clear vision of the general (transnational) perspective. A list of topics includes national and social movements, disputed territories, minorities and refugees, cultural and political transfers. The variegated topics demand expertise in different areas and a trans-disciplinary and inter-disciplinary treatment without regard to established disciplinary boundaries. Systematically applying the transnational and relational perspective to the study of a region as complex as the Balkans has huge cognitive potential and innovative power. The new perspective and cutting-edge methodologies will reveal fresh vistas and bring insights to a number of topics that cannot be restricted in advance. Older research objects will look different and acquire new meanings in the new context and entirely new historical objects will be constituted. The national paradigm of self-contained national histories will be challenged. Such a project may well have wider social and political relevance. There is a positive and integrative value in showing how entangled the histories of the present-day Balkan nations and states were and still are. I would like to imagine such research as promoting good relations rather than fostering divisiveness and separation. This project will also be an input to the European integration of the region, which will hopefully involve the rest of the Balkans in the near future.

1 560 000 €

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

How do extreme electromagnetic fields modify the dynamics of matter? Will quantum electrodynamics effects be important at the focus of an ultra intense laser? How are the magnetospheres of compact stellar remnants formed, and can we capture the physics of these environments in the laboratory? These are all longstanding questions with an overarching connection to extreme plasma physics. Electron-positron pair plasmas are pervasive in all these scenarios. Highly nonlinear phenomena such as QED processes, magnetogenesis, radiation, field dynamics in complex geometries, and particle acceleration, are all linked with the collective dynamics of pair plasmas through mechanisms that remain poorly understood. Building on our state-of-the-art models, on the availability of enormous computational power, and on our recent transformative discoveries on ab initio modelling of plasmas under extreme conditions, the time is ripe to answer these questions in silico. InPairs aims to understand the multidimensional dynamics of electron-positron plasmas under extreme laboratory and astrophysical fields, to determine the signatures of the radiative processes on pair plasmas, and to identify the physics of the magnetospheres of compact stellar remnants, focusing on the electrodynamics of pulsars, that can be mimicked in laboratory experiments using ultra high intensity lasers and charged particle beams. This proposal relies on massively parallel simulations to bridge the gap, for the first time, between the pair plasma creation mechanisms, the collective multidimensional microphysics, and their global dynamics in complex geometries associated with laboratory and astrophysical systems. Emphasis will be given to detectable signatures e.g. radiation and accelerated particles, with the ultimate goal of solving some of the central questions in extreme plasma physics, thus opening new connections between computational studies, laboratory experiments, and relativistic plasma astrophysics.

1 951 124 €

Start date: 2016-09-01, End date: 2021-08-31

The Eurozone crisis forces us to reconsider the conventional wisdom that “Europe” has little effect on national electoral politics. MAPLE’s central goal is to analyse the degree of politicisation the European issue has acquired following the Eurozone crisis, in Belgium, Germany, Greece, Ireland, Portugal and Spain in 2000-2016, and to focus on its consequences for voting behaviour. Our main thesis is that a fundamental shift has occurred in the vote function as a result of this politicisation: short-term factors of voting behaviour, such as economic perceptions as well as leader effects may have been structurally diminished in the countries which have seen bailouts and where citizens increasingly perceive the main policy decisions being directed from Brussels. To measure politicisation of the EU we will analyse both parliamentary debates and media outlets coding for salience and polarisation of the European issue. These measurements will contribute to understand how politicisation of the EU has underpinned political changes between 2000 and 2016 in the countries concerned. The analysis of voting behaviour will employ a social-psychological methodology in order to test the relationship between increased politicisation of the EU and short-term effects. MAPLE will create datasets for 12 newspapers, more than 60 political parties, 26 elections as well as conduct 12 web panel surveys of a representative sample of voters in the countries concerned. MAPLE is interdisciplinary: it combines approaches from social psychology and political science. It includes qualitative data collection (coding of newspapers and parliamentary debates) followed by qualitative and quantitative data analysis. MAPLE will ultimately illuminate the way in which Europe has decisively entered national electoral politics and with what consequences for the vote calculus.

1 592 859 €

Start date: 2016-08-01, End date: 2021-07-31

MUSCLEGUY represents a unique opportunity to commercialize a novel 3D in vitro system for screening and validation of drug candidates to treat muscle disorders. Although skeletal muscle disorders are relatively rare they pose a huge socioeconomic burden. Currently there is a lack of therapeutic options for the majority of patients. This is, for an important part, due to the lack of reliable, reproducible, and physiological relevant in vitro models of muscle disorders that accurately reflect the in vivo reality on which novel therapeutic strategies may be developed. We generated a novel 3D in vitro system of highly matured myofibers, the relevant functional unit of the muscle affected in most muscle disorders and used it to identify novel therapeutic targets of muscle disorders. During MUSCLEGUY, we will further technically optimise our in vitro system to generate human relevant disease models for muscle disorder. Such systems can be used for drug screening and validation. In addition, we will further investigate the commercial feasibility of our product by conducting an elaborate market analysis and establishing a strong IP portfolio. The ultimate aim of MUSCLEGUY is to develop a business plan to convince the relevant stakeholders. Our novel 3D in vitro system for muscle disorder has the potential to meet the requirements for pharmaceutical drug discovery research (HTS format, reproducible and robust) and drastically reduce the associated costs and the number of animals used, in order to further increase the interest of the pharmaceutical industry for muscle disorders.

150 000 €

Start date: 2016-10-01, End date: 2018-03-31

The main objective of POLITICS is to innovate knowledge on anti-racism that brings about a greater understanding of how historically rooted injustices are being challenged by institutions and grassroots movements. Considering the centrality and mutual influence of Europe and Latin America in the global processes of racial formation, POLITICS will develop an inter-disciplinary and comprehensive approach towards two core goals: (a) the analysis of processes of knowledge production about ‘race’ and (anti-)racism in the spheres of (inter)national governmental politics, State universities and grassroots movements; (b) the examination of diverse paths of denunciation and collective mobilisation against everyday racism concerning police practice and representations in the mass media. POLITICS embraces a multilevel analysis and information-oriented selection of case-studies in three interrelated research streams: (i) Global, regional and state-sponsored political frameworks and public policies; (ii) Cultures of scholarship and the study of racism and (post)colonialism at State universities; (iii) Tackling everyday racism: processes of denunciation, political mobilisation and case-law concerning police practice, and racist representations in the media and mass media. The research challenges the shortcomings of evaluative comparisons and the selection of research contexts enables interrogating the relations between the global, national and local levels. They include the Organisation of American States, the European Union and national and local politics in Brazil, Peru, Portugal and Spain. Qualitative research and data collection engage with race critical theories, critical discourse analysis and participatory methods that consider power/knowledge at their core. POLITICS will unravel the configuration of different notions of dignity, justice and equality resulting from anti-racist struggles and policy interventions and their significance for envisaging decolonial horizons.

1 915 381 €

Start date: 2017-09-01, End date: 2022-08-31

There is growing evidence that molecules classically allocated to nervous system function, such as the neurotrophic factors, are produced by lymphocytes and can also regulate their function. The neurotrophic family includes the GDNF ligands (GFLs), which signal through the RET tyrosine kinase receptor. In humans, mutations of the proto-oncogene Ret have been linked to different diseases, such as cancer and Hirschsprung’s disease. Interestingly, RET expression has been reported in lymphocytes but its functional significance is unclear. We propose to use combined genetic, cellular, and molecular approaches in order to determine, quantify and manipulate the function of RET and GFLs during haematopoiesis and lymphocyte differentiation. In order to achieve this, we will analyse the patterns of RET and GFL expression during haematopoiesis, and in mature lymphocyte sub-sets. By using this strategy we aim to identify differentiation stages where the Ret exerts its role. We then plan to assess the functions of RET and candidate GFLs by studying the impact of Ret and GFL gene ablation. To achieve this, we will study lymphoid cells at different stages of differentiation from mice deficient for Ret or GFLs, and determine the role that these molecules play in key cellular and molecular events during haematopoiesis and immune responses. Since RET is likely to exert its function at various differentiation steps, we plan to use genetically modified mice allowing the conditional deletion of Ret. As a complementary approach, we will generate mice over-expressing RET or constitutively activated RET in a tissue-specific manner, thus mimicking activating mutations of RET associated with cancer. We believe our work, apart from its novelty in the field of immunology, will have a broader impact in other disciplines. Indeed, mechanisms historically ascribed to a specific tissue may be used more generally in order to orchestrate the function and communication among different systems.

1 901 400 €

Start date: 2008-11-01, End date: 2013-10-31

Mitochondria at the synapse have a pivotal role in neurotransmitter release, but almost nothing is known about synaptic mitochondria composition or specific functions. Synaptic mitochondria compared to mitochondria in other cells, need to cope with increased calcium load, more oxidative stress, and high demands of energy generation during synaptic activity. My hypothesis is that synaptic mitochondria have acquired specific mechanisms to manage local stress and that disruption of these mechanisms contributes to neurodegeneration. How mitochondria sense their dysfunction is unclear. Even more intriguing is the question how they decide whether their failure should lead to removal of the organelle or dismissal of the complete neuron via cell death. We anticipate that these decisions are not only operational during disease, but might constitute a fundamental mechanism relevant for maintenance of synaptic activity and establishment of new synapses. Recent studies have revealed several genes implicated in neurodegenerative disorders involved in mitochondrial maintenance. However the function of these genes at the synapse, where the initial damage occurs, remains to be clarified. These genes provide excellent starting points to decipher the molecular mechanisms discussed above. Furthermore I propose to use proteomic approaches to identify the protein fingerprint of synaptic mitochondria and to compare them to mitochondria from other tissues. I plan to identify key players of the proposed regulatory pathways involved in intrinsic mitochondria quality control. In a complimentary approach, I will exploit our findings and use in vitro and in vivo experimental approaches to measure mitochondrial function of synaptic versus non-synaptic mitochondria and the relevance of those changes for synaptic function. Our work will unravel the specific properties of synaptic mitochondria and provide much needed insight in their hypothesized predominant role in neurodegenerative disorders.

1 300 000 €

Start date: 2016-09-01, End date: 2021-08-31