ERC FUNDED PROJECTS

Cytokinesis completes cell division by partitioning the contents of the mother cell to the two daughter cells. This process is accomplished through the assembly and constriction of a contractile ring, a complex actomyosin network that remains poorly understood on the molecular level. Research in cytokinesis has overwhelmingly focused on signaling mechanisms that dictate when and where the contractile ring is assembled. By contrast, the research I propose here addresses fundamental questions about the structural and functional properties of the contractile ring itself. We will use the nematode C. elegans to exploit the power of quantitative live imaging assays in an experimentally tractable metazoan organism. The early C. elegans embryo is uniquely suited to the study of the contractile ring, as cells dividing perpendicularly to the imaging plane provide a full end-on view of the contractile ring throughout constriction. This greatly facilitates accurate measurements of constriction kinetics, ring width and thickness, and levels as well as dynamics of fluorescently-tagged contractile ring components. Combining image-based assays with powerful molecular replacement technology for structure-function studies, we will 1) determine the contribution of branched and non-branched actin filament populations to contractile ring formation; 2) explore its ultra-structural organization in collaboration with a world expert in electron microcopy; 3) investigate how the contractile ring network is dynamically remodeled during constriction with the help of a novel laser microsurgery assay that has uncovered a remarkably robust ring repair mechanism; and 4) use a targeted RNAi screen and phenotype profiling to identify new components of actomyosin contractile networks. The results from this interdisciplinary project will significantly enhance our mechanistic understanding of cytokinesis and other cellular processes that involve actomyosin-based contractility.

1 499 989 €

Start date: 2015-07-01, End date: 2020-06-30

The AlchemEast project is devoted to the study of alchemical theory and practice as it appeared and developed in distinct, albeit contiguous (both chronologically and geographically) areas: Graeco-Roman Egypt, Byzantium, and the Near East, from Ancient Babylonian times to the early Islamic Period. This project combines innovative textual investigations with experimental replications of ancient alchemical procedures. It uses sets of historically and philologically informed laboratory replications in order to reconstruct the actual practice of ancient alchemists, and it studies the texts and literary forms in which this practice was conceptualized and transmitted. It proposes new models for textual criticism in order to capture the fluidity of the transmission of ancient alchemical writings. AlchemEast is designed to carry out a comparative investigation of cuneiform tablets as well as a vast corpus of Greek, Syriac and Arabic writings. It will overcome the old, pejorative paradigm that dismissed ancient alchemy as a "pseudo-science", by proposing a new theoretical framework for comprehending the entirety of ancient alchemical practices and theories. Alongside established forms of scholarly output, such as critical editions of key texts, AlchemEast will provide an integrative, longue durée perspective on the many different phases of ancient alchemy. It will thus offer a radically new vision of this discipline as a dynamic and diversified art that developed across different technical and scholastic traditions. This new representation will allow us to connect ancient alchemy with medieval and early modern alchemy and thus fully reintegrate ancient alchemy in the history of pre-modern alchemy as well as in the history of ancient science more broadly.

1 997 000 €

Start date: 2017-12-01, End date: 2022-11-30

"Recent developments in image-making techniques have resulted in a drastic blurring of the threshold between the world of the image and the real world. Immersive and interactive virtual environments have enabled the production of pictures that elicit in the perceiver a strong feeling of being incorporated in a quasi-real world. In doing so such pictures conceal their mediateness (their being based on a material support), their referentiality (their pointing to an extra-iconic dimension), and their separateness (normally assured by framing devices), paradoxically challenging their status as images, as icons: they are veritable “an-icons”. This kind of pictures undermines the mainstream paradigm of Western image theories, shared by major models such as the doctrine of mimesis, the phenomenological account of image-consciousness, the analytic theories of depiction, the semiotic and iconological methods. These approaches miss the key counter-properties regarding an-icons as ""environmental"" images: their immediateness, unframedness, and presentness. Subjects relating to an-icons are no longer visual observers of images; they are experiencers living in a quasi-real environment that allows multisensory affordances and embodied agencies. AN-ICON aims to develop “an-iconology” as a new methodological approach able to address this challenging iconoscape. Such an approach needs to be articulated in a transdisciplinary and transmedial way: 1) HISTORY – a media-archaeological reconstruction will provide a taxonomy of the manifold an-iconic strategies (e.g. illusionistic painting, pre-cinematic dispositifs, 3D films, video games, head mounted displays); 2) THEORY – an experiential account (drawing on phenomenology, visual culture and media studies) will identify the an-iconic key concepts; 3) PRACTICES – a socio-cultural section will explore the multifaceted impact of an-iconic images, environments and technologies on contemporary professional domains as well as on everyday life. "

2 328 736 €

Start date: 2019-09-01, End date: 2024-08-31

From the twelfth to the seventeenth century, Aristotle’s writings lay at the foundation of Western culture, providing a body of knowledge and a set of analytical tools applicable to all areas of human investigation. Scholars of the Renaissance have emphasized the remarkable longevity and versatility of Aristotelianism, but their attention has remained firmly, and almost exclusively, fixed on the transmission of Aristotle’s works in Latin. Scarce attention has gone to works in the vernacular. Nonetheless, several important Renaissance figures wished to make Aristotle’s works accessible and available outside the narrow circle of professional philosophers and university professors. They believed that his works could provide essential knowledge to a broad set of readers, and embarked on an intense programme of translation and commentary to see this happen. It is the argument of this project that vernacular Aristotelianism made fundamental contributions to the thought of the period, anticipating many of the features of early modern philosophy and contributing to a new encyclopaedia of knowledge. Our project aims to offer the first detailed and comprehensive study of the vernacular diffusion of Aristotle through a series of analyses of its main texts. We will thus study works that fall within the two main Renaissance divisions of speculative philosophy (metaphysics, natural philosophy, mathematics, and logic) and civil philosophy (ethics, politics, rhetoric, and poetics). We will give strong attention to the contextualization of the texts they examine, as is standard practice in the best kind of intellectual history, focusing on institutional contexts, reading publics, the value of the vernacular, new visions of knowledge and eclecticism. With the work of the PI, two professors, 5 post-docs and two PhD students we aim to make considerable advances in the understanding of both speculative and civil philosophy within vernacular Aristotelianism.

1 483 180 €

Start date: 2014-05-01, End date: 2019-04-30

Dante Alighieri at the dawn of the 1300s, as well as Eustache Deschamps almost a century later, conceived poetry as music in itself. But what happens with poetry when it is involved in the complex architecture of polyphony? The aim of this project is to study for the first time the corpus of 14th- and early 15th-century poetry set to music by Ars Nova polyphonists (more than 1200 texts). This repertoire gathers different poetic and musical traditions, as shown by the multilingual anthologies copied during the last years of the Schism. The choice of this corpus is motivated by two primary goals: a) to offer a new interpretation of its meaning and function in the cultural and historical context, one that may be then applied to the rest of coeval European lyric poetry; b) to overcome current disciplinary divisions in order to generate a new methodological balance between the project’s two main fields of interest (Comparative Literature / Musicology). Most Ars Nova polyphonists were directly associated with religious institutions. In many texts, the language of courtly love expresses the values of caritas, the theological virtue that guides wise rulers and leads them to desire the common good. Thus, the poetic figure of the lover becomes a metaphor for the political man, and love poetry can be used as a device for diplomacy, as well as for personal and institutional propaganda. From this unprecedented point of view, the project will develop three research lines in response to the following questions: 1) How is the relationship between poetry and music, and how is the dialogue between the different poetic and musical traditions viewed in relation to each context of production? 2) To what extent does Ars Nova poetry take part in the ‘soft power’ strategies exercised by the entire European political class of the time? 3) Is there a connection between the multilingualism of the manuscript tradition and the perception of the Ars Nova as a European, intercultural repertoire?

2 193 375 €

Start date: 2019-01-01, End date: 2023-12-31

Development economists and policymakers often face scenarios in which poor people do not make choices that would help them get out of poverty due to an “aspiration failure”: the poor perceive certain goals as unattainable and do not invest towards those goals, thus perpetuating their own state of poverty. The aim of this proposal is to improve our understanding of the relationship between aspirations and socio-economic outcomes of disadvantaged individuals, in order to answer the question: Can we design policy interventions that shift aspirations in a way that is conducive to development? In addressing the above question a fundamental role is played by social norms and by the ability of individuals to coordinate on “new” aspirations, hence the analysis of social effects is a salient feature of this proposal. The proposed research is organized in two workpackages. The first focuses on the media as a vehicle for changing aspirations, examining both commercial TV programs and “educational entertainment”. The second workpackage examines “tailored” interventions designed to address specific determinants of aspiration failures (e.g., psychological support to reduce perceived barriers; inter-racial interaction to change stereotypes; institutional reform to strengthen women’s rights and reduce the gender aspiration gap). The methodology will involve rigorous evaluation of several interventions directly designed to or indirectly affecting aspirations and social norms. Original data collected through survey work, large administrative datasets and media content analysis will be used. The results of this project will advance our knowledge on the sources of aspiration failures by poor people and on the interplay between aspirations and social norms, eventually opening the avenue for a new array of anti-poverty policies.

1 618 125 €

Start date: 2016-11-01, End date: 2021-10-31

Since the invention of the spinning frame, automation has been one of the drivers of economic growth. Yet, workers, economist or the general public have been concerned that automation may destroy jobs or create inequality. This concern is particularly prevalent today with the sustained rise in economic inequality and fast technological progress in IT, robotics or self-driving cars. The empirical literature has showed the impact of automation on income distribution. Yet, the level of wages itself should also affect the incentives to undertake automation innovations. Understanding this feedback is key to assess the long-term effect of policies. My project aims to provide the first quantitative account of the two-way relationship between automation and the income distribution. It is articulated around three parts. First, I will use patent data to study empirically the causal effect of wages on automation innovations. To do so, I will build firm-level variation in the wages of the customers of innovating firms by exploiting variations in firms’ exposure to international markets. Second, I will study empirically the causal effect of automation innovations on wages. There, I will focus on local labour market and use the patent data to build exogenous variations in local knowledge. Third, I will calibrate an endogenous growth model with firm dynamics and automation using Danish firm-level data. The model will replicate stylized facts on the labour share distribution across firms. It will be used to compute the contribution of automation to economic growth or the decline of the labour share. Moreover, as a whole, the project will use two different methods (regression analysis and calibrated model) and two different types of data, to answer questions of crucial policy importance such as: Taking into account the response of automation, what are the long-term effects on wages of an increase in the minimum wage, a reduction in labour costs, or a robot tax?

1 295 890 €

Start date: 2018-11-01, End date: 2023-10-31

Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.

2 200 000 €

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

The proposed project offers a new, pan-European intellectual history of the political imagination in the interwar period that places the demise of historicism and progressivism – and the emerging anti-teleological visions of time – at the center of some of its most innovative ethical, political and methodological pursuits. It argues that only a distinctively cross-disciplinary and European narrative can capture the full ramifications and legacies of a fundamental rupture in thought conventionally, yet inadequately confined to the German cultural space and termed “anti-historicism”. It innovates narratively by exploring politically and theoretically interlaced reinventions of temporality across and between different disciplines (theology, jurisprudence, classical studies, literary theory, linguistics, sociology, philosophy), as well as other creative fields. It experiments methodologically by reconstructing the dynamics of political thought prosopographically, through intellectual groupings at the forefront of the scholarly and political debates of the period. It challenges the sufficiency of the standard focus in interwar intellectual history on one or two, at most three (usually “Western” European) national contexts by following out the interactions of these groupings in France, Britain, Germany, Russia, Czechoslovakia, and Romania – groupings whose members frequently moved across national contexts. What were the political languages encoded in the reinventions of time, and vice versa – how were political aims translated into and advanced through theoretical innovation? How did these differ in different national contexts, and why? What are the fragmented legacies of this rupture, disbursed in and through the philosophical, methodological and political dicta and dogmas that rooted themselves in post-1945 thought? This project provides the first comprehensive answer to these fundamental questions about the intellectual identity of Europe and its historicities.

1 425 000 €

Start date: 2018-06-01, End date: 2023-05-31

Shape Memory Alloys (SMAs) are nowadays widely exploited for the realization of innovative devices and have a great impact on the development of a variety of biomedical applications ranging from orthodontic archwires to vascular stents. The design, realization, and optimization of such devices are quite demanding tasks. Mathematics is involved in this process as a major tool in order to let the modeling more accurate, the numerical simulations more reliable, and the design more effective. Many material properties of SMAs such as martensitic reorientation, training, and ferromagnetic behavior, are still to be properly and efficiently addressed. Therefore, new modeling ideas, along with original analytical and numerical techniques, are required. This project is aimed at addressing novel mathematical issues in order to move from experimental materials results toward the solution of real-scale biomechanical Engineering problems. The research focus will be multidisciplinary and include modeling, analytic, numerical, and computational issues. A progress in the macroscopic description of SMAs, the computational simulation of real-scale SMA devices, and the optimization of the production processes will contribute to advance in the direction of innovative applications.

700 000 €

Start date: 2008-09-01, End date: 2013-08-31

Corruption is a global challenge that affects the lives of millions of citizens. In the past decade, Information and Communication Technologies (ICTs) have become indispensable tools in the fight to reduce corruption, especially when employed from the bottom-up by civil society organizations. While pioneering initiatives in this direction have flourished, to date we only have unsystematic and descriptive evidence regarding how they work and the associated consequences. With the objective of significantly advancing knowledge on this topic, BIT-ACT will open a new line of inquiry by investigating what I call anti-corruption technologies (ACTs) to: (1) assess how civil society organizations engage with ACTs to counter corruption, (2) appraise how ACTs enable intersections between bottom-up and top-down efforts against corruption, and (3) evaluate how ACTs blend with the transnational dimension in the struggle against corruption. Based on an interdisciplinary framework that combines corruption studies, science and technology studies and social movement studies, BIT-ACT will use the constructivist grounded theory method to analyze a combination of textual and visual data in a comparative and transnational research design including nine countries – Algeria, Bangladesh, Brazil, Estonia, India, Italy, Spain, Ukraine, Uruguay. BIT-ACT will be groundbreaking in three ways. At the theoretical level, it will expand the debate on anti-corruption providing grounded concepts and models to explain ACTs; at the empirical level, it will advance knowledge on how the usage of ACTs is changing the relationship between citizens and democratic institutions; at the methodological level, it will innovate in the use of grounded theory assessing a new standard for cross-national comparative grounded theory. Finally, BIT-ACT will produce sound and useful knowledge for the stakeholders involved in the fight against corruption worldwide by suggesting how to best employ ICTs from the bottom-up.

1 489 115 €

Start date: 2019-07-01, End date: 2024-06-30

While the crisis of the territorial nation-state in the Middle East has once again been brought to a head by the wars in Iraq and Syria, it cannot be simply understood as the logical consequence of an imported political construction. Based on two epistemological notions – borderlands as histoire-problème (history-as-problem) and the co-production of borders between state and society – this research project proposes to rethink the classical historical narrative about the emergence of the post-Ottoman Middle East. Taking its cue from trans-border phenomena and thus paying attention to the circulation of people, goods and ideas as well as to everyday encounters between local actors and state representatives, the project will be guided by four principle objectives to offer: • A socio-historical analysis of state violence in the borderlands of the Middle East; • An examination of the capacity of border populations to create the history of the borderlands, nation-states, and the region as a whole; • A study of the frontier effects based around the notions of subjectivity, space and time, and involving various levels of observation (macro, meso and micro) in order to identify the ruptures and continuities evoked by the delineation of new borderlines; and • A historical lens through which to make sense of current events in Syria and Iraq, and possibly orient conflict-resolution practitioners. Through the exploitation of a wide range of sources (diplomatic, administrative and military records, missionary documents, newspapers) and by looking at the social construction of international frontiers at the borderlands located between Turkey, Iraq and Syria in the interwar era, the research project will provide a much more holistic yet finely-grained understanding of the formation of the territorial state in the region in the aftermath of the First World War as well as a historical perspective on the on-going armed conflicts.

1 997 675 €

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

Successful social interactions require social decision making, the ability to guide our actions in line with the goals and expectations of the people around us. Disordered social decision making – e.g., associated with criminal activity or psychiatric illnesses – poses significant financial and personal challenges to society. However, the brain mechanisms that enable us to control our social behavior are far from being understood. Here I will take decisive steps towards a causal understanding of these mechanisms by elucidating the role of functional interactions in the brain networks responsible for steering strategic, prosocial, and norm-compliant behavior. I will employ a unique multi-method approach that integrates computational modeling of social decisions with new combinations of multimodal neuroimaging and brain stimulation methods. Using EEG-fMRI, I will first identify spatio-temporal patterns of functional interactions between brain areas that correlate with social decision processes as identified by computational modeling of behavior in different economic games. In combined brain stimulation-fMRI studies, I will then attempt to affect – and in fact enhance – these social decision-making processes by modulating the identified brain network patterns with novel, targeted brain stimulation protocols and measuring the resulting effects on behavior and brain activity. Finally, I will examine whether the identified brain network mechanisms are indeed related to disturbed social decisions in two psychiatric illnesses characterized by maladaptive social behavior (post-traumatic stress disorder and autism spectrum disorder). My proposed work plan will generate a causal understanding of the brain network mechanisms that allow humans to control their social decisions, thereby elucidating a biological basis for individual differences in social behavior and paving the way for new perspectives on how disordered social behavior may be identified and hopefully remedied.

1 999 991 €

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

In the field of economics, individual decision making is the basic building block for studying complex environments such as markets, political systems, and social dynamics. Individual decision making is embodied in the neoclassical economically rational agent, whose only concern is the maximization of utility from his own material consumption. Two qualities of this agent are especially important for the research we will undertake: He has perfect understanding of the problems he faces - today and in the future - and unbounded computational ability to solve them. He also has no regard for the consumption of other members of the society or for their feelings about his actions. Huge empirical and experimental evidence shows that departure from these qualities is robust and significant. The failure of the existing models to incorporate bounded rationality and social concerns has proven critical in socially relevant and complex situations such as lifetime consumption and saving, taxation and expenditure policy, labour search and wage determination. The objective of this project is to bring these phenomena into the framework of neoclassical economics, to test their implications, and to tackle important applications. A novel and central feature of our approach is the attempt to retain the parsimonious methodological approach of economic modelling, which has scored groundbreaking successes in matters such as the design of auctions, markets, contracts, and voting mechanisms. Our project envisions the development of theory on individual decision making, the use of experiments to illuminate and test the theory, and the concrete application of theory - mainly to financial markets. The project will push the frontiers of the understanding of the above mentioned socially relevant situations. The explanatory power of our approach will be guaranteed by the continuous feed-back between theory and evidence- experimental and neuroexperimental, and by a departure from ad hoc modelling.

1 399 800 €

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

Understanding cause-effect relationships between variables is of great interest in many fields of science. However, causal inference from data is much more ambitious and difficult than inferring (undirected) measures of association such as correlations, partial correlations or multivariate regression coefficients, mainly because of fundamental identifiability problems. A main objective of the proposal is to exploit advantages from large-scale heterogeneous data for causal inference where heterogeneity arises from different experimental conditions or different unknown sub-populations. A key idea is to consider invariance or stability across different experimental conditions of certain conditional probability distributions: the invariants correspond on the one hand to (properly defined) causal variables which are of main interest in causality; andon the other hand, they correspond to the features for constructing powerful predictions for new scenarios which are unobserved in the data (new probability distributions). This opens novel perspectives: causal inference can be phrased as a prediction problem of a certain kind, and vice versa, new prediction methods which work well across different scenarios (unobserved in the data) should be based on or regularized towards causal variables. Fundamental identifiability limits will become weaker with increased degree of heterogeneity, as we expect in large-scale data. The topic is essentially unexplored, yet it opens new avenues for causal inference, structural equation and graphical modeling, and robust prediction based on large-scale complex data. We will develop mathematical theory, statistical methodology and efficient algorithms; and we will also work and collaborate on major application problems such as inferring causal effects (i.e., total intervention effects) from gene knock-out or RNA interference perturbation experiments, genome-wide association studies and novel prediction tasks in economics.

2 184 375 €

Start date: 2018-10-01, End date: 2023-09-30

The molecular mechanisms that mediate cell competition, cell fitness and cell selection is gaining interest. With innovative approaches, molecules and ground-breaking hypothesis, this field of research can help understand several biological processes such as development, cancer and tissue degeneration. The project has 3 clear and ambitious objectives: 1. We propose to identify all the key genes mediating cell competition and their molecular mechanisms. In order to reach this objective we will use data from two whole genome screens in Drosophila where we have identified 7 key genes. By the end of this CoG grant, we should have no big gaps in our knowledge of how slow dividing cells are recognised and eliminated in Drosophila. 2. In addition, we will explore how general the cell competition pathways are and how they can impact biomedical research, with a focus in cancer and tissue degeneration. The interest in cancer is based on experiments in Drosophila and mice where we and others have found that an active process of cell selection determines tumour growth. Preliminary results suggest that the pathways identified do not only play important roles in the elimination of slow dividing cells, but also during cancer initiation and progression. 3. We will further explore the role of cell competition in neuronal selection, specially during neurodegeneration, development of the retina and adult brain regeneration in Drosophila. This proposal is of an interdisciplinary nature because it takes a basic cellular mechanism (the genetic pathways that select cells within tissues) and crosses boundaries between different fields of research: development, cancer, regeneration and tissue degeneration. In this ERC CoG proposal, we are committed to continue our efforts from basic science to biomedical approaches. The phenomena of cell competition and its participating genes have the potential to discover novel biomarkers and therapeutic strategies against cancer and tissue degeneration.

1 968 062 €

Start date: 2014-06-01, End date: 2019-05-31

Centrosome duplication entails the formation of a single procentriole next to each centriole once per cell cycle. The mechanisms governing procentriole formation are poorly understood and constitute a fundamental open question in cell biology. We will launch an innovative multidisciplinary research program to gain significant insight into these mechanisms using C. elegans and human cells. This research program is also expected to have a significant impact by contributing important novel assays to the field. Six specific aims will be pursued: 1) SAS-6 as a ZYG-1 substrate: mechanisms of procentriole formation in C. elegans. We will test in vivo the consequence of SAS-6 phosphorylation by ZYG-1. 2) Biochemical and structural analysis of SAS-6-containing macromolecular complexes (SAMACs). We will isolate and characterize SAMACs from C. elegans embryos and human cells, and analyze their structure using single-particle electron microscopy. 3) Novel cell-free assay for procentriole formation in human cells. We will develop such an assay and use it to test whether SAMACs can direct procentriole formation and whether candidate proteins are needed at centrioles or in the cytoplasm. 4) Mapping interactions between centriolar proteins in live human cells. We will use chemical methods developed by our collaborators to probe interactions between HsSAS-6 and centriolar proteins in a time- and space-resolved manner. 5) Functional genomic and chemical genetic screens in human cells. We will conduct high-throughput fluorescence-based screens in human cells to identify novel genes required for procentriole formation and small molecule inhibitors of this process. 6) Mechanisms underlying differential centriolar maintenance in the germline. In C. elegans, we will characterize how the sas-1 locus is required for centriole maintenance during spermatogenesis, as well as analyze centriole elimination during oogenesis and identify components needed for this process

2 004 155 €

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

Deciphering and engineering the assembly of cellular organelles is a key pursuit in biology. The centriole is an evolutionarily conserved organelle well suited for this goal, and which is crucial for cell signaling, motility and division. The centriole exhibits a striking 9-fold radial symmetry of microtubules around a likewise symmetrical cartwheel containing stacked ring-bearing structures. Components essential for generating this remarkable architecture from alga to man have been identified. A next critical step is to engineer assays to probe the dynamics of centriole assembly with molecular precision to fully understand how these components together build a functional organelle. Our ambitious research proposal aims at taking groundbreaking steps in this direction through four specific aims: 1) Reconstituting cartwheel ring assembly dynamics. We will use high-speed AFM (HS-AFM) to dissect the biophysics of SAS-6 ring polymer dynamics at the root of cartwheel assembly. We will also use HS-AFM to analyze monobodies against SAS-6, as well as engineer surfaces and DNA origamis to further dissect ring assembly. 2) Deciphering ring stacking mechanisms. We will use cryo-ET to identify SAS-6 features that direct stacking of ring structures and set cartwheel height. Moreover, we will develop an HS-AFM stacking assay and a reconstituted stacking assay from human cells. 3) Understanding peripheral element contributions to centriole biogenesis. We will dissect the function of the peripheral centriole pinhead protein Cep135/Bld10p, as well as identify and likewise dissect peripheral A-C linker proteins. Furthermore, we will further engineer the HS-AFM assay to include such peripheral components. 4) Dissecting de novo centriole assembly mechanisms. We will dissect de novo centriole formation in human cells and water fern. We will also explore whether de novo formation involves a phase separation mechanism and repurpose the HS-AFM assay to probe de novo organelle biogenes

2 500 000 €

Start date: 2019-09-01, End date: 2024-08-31

Centrioles are essential for the formation of several microtubule organizing structures including cilia, flagella and centrosomes. These structures are involved in a variety of functions, from cell motility to division. Centrosome defects are seen in many cancers, while abnormalities in cilia and flagella can lead to a variety of human diseases, such as polycystic kidney disease. The molecular mechanisms regulating centriole biogenesis have only recently started to be unravelled, opening new ways to answer a wide range of questions that have fascinated biologists for more than a century. In this grant we are asking two fundamental questions that are central to human disease: how is centriole structure and number established and regulated in the eukaryotic cell? To address these questions we propose to identify new molecular players, and to test the role of these and known players in the context of specific mechanistic hypothesis, using in vitro and in vivo models. We propose to develop novel assays for centriole structure and regulation in order to address mechanistic problems not accessible with today s assays. In our search for novel components we will use a multidisciplinary approach combining bioinformatics with high throughput screening. The use of in vitro systems will permit the quantitative dissection of molecular mechanisms, while the study of those mechanisms in Drosophila will allow us to understand them at the whole organism level. Furthermore, this analysis, together with studies in human tissue culture cells, will allow us to understand the consequences of misregulation of these fundamental centriole properties for human disease, such as ciliopathies and cancer. My group is already collaborating with medical doctors in the study of centriole aberrations in human disease (cancer and ciliopathies), which will be invaluable to bringing the results of this study to the translational level.

1 500 000 €

Start date: 2011-01-01, End date: 2016-12-31

Genome stability relies on accurate partition of the genome during nuclear division. Proper mitosis, in turn, depends on changes in chromosome organization, such as chromosome condensation and sister chromatid cohesion. Despite the importance of these structural changes, chromatin itself has been long assumed to play a rather passive role during mitosis and chromosomes are usually compared to a “corpse at a funeral: they provide the reason for the proceedings but do not take an active part in them.” (Mazia, 1961). Recent evidence, however, suggests that chromosomes play a more active role in the process of their own segregation. The present proposal tests the “active chromosome” hypothesis by investigating how chromosome morphology influences the fidelity of mitosis. I will use innovative methods for acute protein inactivation, developed during my postdoctoral studies, to evaluate the role of two key protein complexes involved in mitotic chromosome architecture - Condensins and Cohesins. Using a multidisciplinary approach, combining acute protein inactivation, 3D-live cell imaging and quantitative methods, I propose to investigate the role of mitotic chromosomes in the fidelity of mitosis at three different levels. The first one will use novel approaches to uncover the process of mitotic chromosome assembly, which is still largely unknown. The second will explore how mitotic chromosomes take an active part in mitosis by examining how chromosome condensation and cohesion influence chromosome movement and the signalling of the surveillance mechanisms that control nuclear division. Lastly we will evaluate how mitotic errors arising from abnormal chromosome structure impact on development. We aim to evaluate, at the cellular and organism level, how the cell perceives such errors and how (indeed if) they tolerate mitotic abnormalities. By conceptually challenging the passive chromosome view this project has the potential to redefine the role of chromatin during mitosis.

1 492 000 €

Start date: 2015-10-01, End date: 2020-09-30

This project is devoted to the mathematical analysis of important physical properties of many-body quantum systems. We will be interested in properties of the ground state and low-energy excitations but also of non-equilibrium dynamics. We are going to consider systems with different statistics and in different regimes. The questions we are going to address have a common aspect: correlations among particles play a crucial role. Our main goal consists in developing new tools that allow us to correctly describe many-body correlations and to understand their effects. The starting point of our proposal are ideas and techniques that have been introduced in a series of papers establishing the validity of Bogoliubov theory for Bose gases in the Gross-Pitaevskii regime, and in a recent preprint showing how (bosonic) Bogoliubov theory can also be used to study the correlation energy of Fermi gases. In this project, we plan to develop these techniques further and to apply them to new contexts. We believe they have the potential to approach some fundamental open problem in mathematical physics. Among our most ambitious objectives, we include the proof of the Lee-Huang-Yang formula for the energy of dilute Bose gases and of the corresponding Huang-Yang formula for dilute Fermi gases, as well as the derivation of the Gell-Mann--Brueckner expression for the correlation energy of a high density Fermi system. Furthermore, we propose to work on long-term projects (going beyond the duration of the grant) aiming at a rigorous justification of the quantum Boltzmann equation for fermions in the weak coupling limit and at a proof of Bose-Einstein condensation in the thermodynamic limit, two very challenging and important questions in the field.

1 876 050 €

Start date: 2019-09-01, End date: 2024-08-31

The European dimension of administrative law is the focus of a flurry of initiatives aiming to investigate similarities and differences, and to shape common legal scenarios. A codification of the administrative procedures of the EU has been envisaged by the European Parliament in its resolution of February 2013. A broader proposal of codification, including rule-making and contractual procedures, has been elaborated by ReNEUAL and has been discussed in a series of workshops in 2015. The issues that arise are both practical and theoretical: - it is important to understand whether the method traditionally followed by the European Court of Justice in order to identify the principles that are general and common to national legal systems, only applies when all those systems recognize such principles; - whether national systems of public law share the same idea of what an administrative procedure is is another question; whether the specific principles governing administrative procedures, such as the right to be heard and the duty to give reasons, are the same is still another question; - finally, if any commonality exists, the question that arises is whether it is limited to the level of general principles of law or it includes the which govern procedures. The research project is innovative on grounds of method, because: - it aims at ascertaining whether, and the extent to that, the well-established methodology developed under the ‘Common Core of European Private Law’ project can be applied to EU administrative law; - it permits to distinguish between ‘operative rules’, ‘descriptive formants’, and ‘meta-legal formants’; - it also allows to understand whether the specific nature of the interests recognized and protected by the rules of public law require legal methodologies that are distinct and distant from those of private law.

1 254 105 €

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

The project will be using the Gender and Generations Surveys (GGS) – a system of comparable micro-level surveys for several Developed countries – to analyse the consequences of demographic change. The analysis will be using households and individuals as the unit of observation. As a result, we will be able to make inferences about how certain demographic behaviours (i.e. childbearing, marital disruption, single motherhood, leaving home), including their timing and sequencing, affect certain outcomes, such as income, poverty, deprivation, together with various child outcomes. This analysis is particularly relevant given recent demographic trends in developed countries (e.g. divorce rates are increasing, out-of-wedlock childbearing is becoming more prevalent, and general delay in key demographic events such as childbearing and leaving the parental home). The novelty of the study is driven by its focus on consequences of newly emerging demographic patterns and behaviour, which is in contrast to the majority of previous demographic studies – which has tended to focus on the determinants behind these trends. Policy analysis has not had a strong tradition in Demography and the aim of this project is to rectify this shortcoming of the discipline. By focusing on the consequences of demographic change and using techniques that are borrowed from program evaluation, econometrics, applied statistics and empirical sociology, we aim to advance the understanding of how demographic events impact other important processes in the life course of individuals and how policy makers can best influence such outcomes by appropriate policy interventions.

750 000 €

Start date: 2008-07-01, End date: 2013-06-30

This project is about the racialization of migrant labourers across political boundaries, with a main focus on impoverished Europeans who served in huge numbers as indentured labourers in nineteenth-century Guianese, Caribbean and Hawaiian sugar plantations and in the workforce of late nineteenth and early twentieth century New England cotton mills. With this project I aim to provide major, innovative contributions on three fronts: (i) theory-making, by working the concepts of race, racism, racialization, embodiment and memory in association with migrant work across political boundaries and imperial classifications; (ii) social relevance of basic research, by linking an issue of pressing urgency in contemporary Europe to substantive, broad-scope, and multi-sited anthropological/historical research on the wider structures of domination, rather than to targeted problem-solving research of immediate applicability; (iii) disciplinary scope, by proposing to unsettle historical anthropology and ethnographic history from within the boundaries of a single empire, and to overcome the limitations of existing comparative studies, by inquiring into the flows and interactions between competing empires. I will also: (iv) strengthen the methodology for multi-sited, multi-period research in anthropology; (v) contribute to an anthropology of global connections and trans-local approaches; (vi) promote the multidisciplinary and combined-methods approach to complex subjects; (vii) narrate a poorly known set of historical situations of labour racializations involving Europeans and document the ways they reverberate through generations; and (viii) make the analysis available to both academic audiences and the different communities involved in the research.

2 161 397 €

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