ERC FUNDED PROJECTS

Listening in realistic situations is an active process that engages perceptual and cognitive faculties, endowing speech with meaning, music with joy, and environmental sounds with emotion. Through hearing, humans and other animals navigate complex acoustic scenes, separate sound mixtures, and assess their behavioral relevance. These remarkable feats are currently beyond our understanding and exceed the capabilities of the most sophisticated audio engineering systems. The goal of the proposed research is to investigate experimentally a novel view of hearing, where active hearing emerges from a deep interplay between adaptive sensory processes and goal-directed cognition. Specifically, we shall explore the postulate that versatile perception is mediated by rapid-plasticity at the neuronal level. At the conjunction of sensory and cognitive processing, rapid-plasticity pervades all levels of auditory system, from the cochlea up to the auditory and prefrontal cortices. Exploiting fundamental statistical regularities of acoustics, it is what allows humans and other animal to deal so successfully with natural acoustic scenes where artificial systems fail. The project builds on the internationally recognized leadership of the PI in the fields of physiology and computational modeling, combined with the expertise of the Co-Investigator in psychophysics. Building on these highly complementary fields and several technical innovations, we hope to promote a novel view of auditory perception and cognition. We aim also to contribute significantly to translational research in the domain of signal processing for clinical hearing aids, given that many current limitations are not technological but rather conceptual. The project will finally result in the creation of laboratory facilities and an intellectual network unique in France and rare in all of Europe, combining cognitive, neural, and computational approaches to auditory neuroscience.

3 199 078 €

Start date: 2012-10-01, End date: 2018-09-30

"In plants, receptor kinases form the largest family of plasma membrane (PM) receptors and they are involved in virtually all aspects of the plant life, including development, immunity and reproduction. In animals, key molecules that orchestrate the recruitment of signaling proteins to membranes are anionic phospholipids (e.g. phosphatidylinositol phosphate or PIPs). Besides, recent reports in animal and yeast cells suggest the existence of PM nanodomains that are independent of cholesterol and lipid phase and rely on anionic phospholipids as well as electrostatic protein/lipid interactions. Strikingly, we know very little on the role of anionic phospholipids in plant signaling. However, our preliminary data suggest that BKI1, an inhibitory protein of the steroid receptor kinase BRI1, interacts with various PIPs in vitro and is likely targeted to the PM by electrostatic interactions with these anionic lipids. These results open the possibility that BRI1, but also other receptor kinases, might be regulated by anionic phospholipids in plants. Here, we propose to analyze the function of anionic phospholipids in BRI1 signaling, using the root epidermis as a model system. First, we will ask what are the lipids that control membrane surface charge in this tissue and recruit BR-signaling component to the PM. Second, we will probe the presence of PIP-enriched nanodomains at the plant PM using super-resolution microscopy techniques and investigate the roles of these domains in BRI1 signaling. Finally, we will analyze the function of the BKI1-related plant-specific family of anionic phospholipid effectors in plant development. In summary, using a transversal approach ranging from in vitro studies to in vivo validation and whole organism physiology, this work will unravel the interplay between anionic phospholipids and receptor signaling in plants."

1 797 840 €

Start date: 2014-02-01, End date: 2019-01-31

Cellular organelles are continuously remodelled by numerous cytosolic proteins that associate transiently with their lipid membrane. Some distort the bilayer, others change its composition, extract lipids or bridge membranes at distance. Previous works from my laboratory have underlined the importance of membrane sensors, i.e. elements within proteins that help to organize membrane-remodelling events by sensing the physical and chemical state of the underlying membrane. A membrane sensor is not necessarily of well-folded domain that interacts with a specific lipid polar head: some intrinsically unfolded motifs harboring deceptively simple sequences can display remarkable membrane adhesive properties. Among these are some amphipathic helices: the ALPS motif with a polar face made mostly by small uncharged polar residues, the Spo20 helix with several histidines in its polar face and, like a mirror image of the ALPS motif, the alpha-synuclein helix with very small hydrophobic residues. Using biochemistry and molecular dynamics, we will compare the membrane binding properties of these sequences (effect of curvature, charge, lipid unsaturation); using bioinformatics we will look for new motifs, using cell biology we will assess the adaptation of these motifs to the physical and chemical features of organelle membranes. Concurrently, we will use reconstitution approaches on artificial membranes to dissect how membrane sensors contribute to the organization of vesicle tethering by golgins and sterol transport by ORP proteins. We surmise that the combination of a molecular ¿switch¿, a small G protein of the Arf family, and of membrane sensors permit to organize these complex reactions in time and in space.

1 997 321 €

Start date: 2011-05-01, End date: 2015-04-30

The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved. The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language. The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.

1 621 250 €

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

When triggered by nutrient limitation, the Gram-positive bacterium Bacillus subtilis and its relatives enter a pathway of cellular differentiation culminating in the formation of a dormant cell type called a spore, the most resilient cell type known. Bacterial spores can survive for long periods of time and are able to endure extremes of heat, radiation and chemical assault. Remarkably, dormant spores can rapidly convert back to actively growing cells by a process called germination. Consequently, spore forming bacteria, including dangerous pathogens, (such as C. botulinum and B. anthracis) are highly resistant to antibacterial treatments and difficult to eradicate. Despite significant advances in our understanding of the process of spore formation, little is known about the nature of the mature spore. It is unrevealed how dormancy is maintained within the spore and how it is ceased, as the organization and the dynamics of the spore macromolecules remain obscure. The unusual biochemical and biophysical characteristics of the dormant spore make it a challenging biological system to investigate using conventional methods, and thus set the need to develop innovative approaches to study spore biology. We propose to explore the nature of spores by using B. subtilis as a primary experimental system. We intend to: (1) define the architecture of the spore chromosome, (2) track the complexity and fate of mRNA and protein molecules during sporulation, dormancy and germination, (3) revisit the basic notion of the spore dormancy (is it metabolically inert?), (4) compare the characteristics of bacilli spores from diverse ecophysiological groups, (5) investigate the features of spores belonging to distant bacterial genera, (6) generate an integrative database that categorizes the molecular features of spores. Our study will provide original insights and introduce novel concepts to the field of spore biology and may help devise innovative ways to combat spore forming pathogens.

1 630 000 €

Start date: 2008-10-01, End date: 2013-09-30

The Bantu Expansion is not only the main linguistic, cultural and demographic process in Late Holocene Africa. It is also one of the most controversial issues in African History that still has political repercussions today. It has sparked debate across the disciplines and far beyond Africanist circles in an attempt to understand how the young Bantu language family (ca. 5000 years) could spread over large parts of Central, Eastern and Southern Africa. This massive dispersal is commonly seen as the result of a single migratory macro-event driven by agriculture, but many questions about the movement and subsistence of ancestral Bantu speakers are still open. They can only be answered through real interdisciplinary collaboration. This project will unite researchers with outstanding expertise in African archaeology, archaeobotany and historical linguistics to form a unique cross-disciplinary team that will shed new light on the first Bantu-speaking village communities south of the rainforest. Fieldwork is planned in parts of the Democratic Republic of Congo, the Republic of Congo and Angola that are terra incognita for archaeologists to determine the timing, location and archaeological signature of the earliest villagers and to establish how they interacted with autochthonous hunter-gatherers. Special attention will be paid to archaeobotanical and palaeoenvironmental data to get an idea of their subsistence, diet and habitat. Historical linguistics will be pushed beyond the boundaries of vocabulary-based phylogenetics and open new pathways in lexical reconstruction, especially regarding subsistence and land use of early Bantu speakers. Through interuniversity collaboration archaeozoological, palaeoenvironmental and genetic data and phylogenetic modelling will be brought into the cross-disciplinary approach to acquire a new holistic view on the interconnections between human migration, language spread, climate change and early farming in Late Holocene Central Africa.

1 997 500 €

Start date: 2018-01-01, End date: 2022-12-31

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

The goal of this proposal is to deliver a new theoretical framework to understand how transcription factors (TFs) sustain cell identity during developmental processes. Recognised as key drivers of cell fate acquisition, TFs are currently not considered to directly contribute to the mitotic inheritance of chromatin states. Instead, these are passively propagated through cell division by a variety of epigenetic marks. Recent discoveries, including by our lab, challenge this view: developmental TFs may impact the propagation of regulatory information from mother to daughter cells through a process known as mitotic bookmarking. This hypothesis, largely overlooked by mainstream epigenetic research during the last two decades, will be investigated in embryo-derived stem cells and during early mouse development. Indeed, these immature cell identities are largely independent from canonical epigenetic repression; hence, current models cannot account for their properties. We will comprehensively identify mitotic bookmarking factors in stem cells and early embryos, establish their function in stem cell self-renewal, cell fate acquisition and dissect how they contribute to chromatin regulation in mitosis. This will allow us to study the relationships between bookmarking factors and other mechanisms of epigenetic inheritance. To achieve this, unique techniques to modulate protein activity and histone modifications specifically in mitotic cells will be established. Thus, a mechanistic understanding of how mitosis influences gene regulation and of how mitotic bookmarking contributes to the propagation of immature cell identities will be delivered. Based on robust preliminary data, we anticipate the discovery of new functions for TFs in several genetic and epigenetic processes. This knowledge should have a wide impact on chromatin biology and cell fate studies as well as in other fields studying processes dominated by TFs and cell proliferation.

1 900 844 €

Start date: 2018-09-01, End date: 2023-08-31

My lab is interested in the development of the tissue that gives rise to vertebrae and skeletal muscles called the paraxial mesoderm. A striking feature of this tissue is its segmental organization and we have made major contributions to the understanding of the molecular control of the segmentation process. We identified a molecular oscillator associated to the rhythmic production of somites and proposed a model for vertebrate segmentation based on the integration of a rhythmic signaling pulse gated spatially by a system of traveling FGF and Wnt signaling gradients. We are also studying the differentiation of paraxial mesoderm precursors into the muscle, cartilage and dermis lineages. Our work identified the Wnt, FGF and Notch pathways as playing a prominent role in the patterning and differentiation of paraxial mesoderm. In this application, we largely focus on the molecular control of paraxial mesoderm development. Using microarray and high throughput sequencing-based approaches and bioinformatics, we will characterize the transcriptional network acting downstream of Wnt, FGF and Notch in the presomitic mesoderm (PSM). We will also use genetic and pharmacological approaches utilizing real-time imaging reporters to characterize the pacemaker of the segmentation clock in vivo, and also in vitro using differentiated embryonic stem cells. We further propose to characterize in detail a novel RA-dependent pathway that we identified and which controls the somite left-right symmetry. Our work is expected to have a strong impact in the field of congenital spine anomalies, currently an understudied biomedical problem, and will be of utility in elucidating the etiology and eventual prevention of these disorders. This work is also expected to further our understanding of the Notch, Wnt, FGF and RA signalling pathways which are involved in segmentation and in the establishment of the vertebrate body plan, and which play important roles in a wide array of human diseases.

2 500 000 €

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

"During their first year of life, infants become attuned to the phonemes, words and phonological rules of their language, with little or no adult supervision. After 30 years of accumulated experimental results, we are still lacking an account for the puzzling fact that these 3 interdependent components of language are acquired not sequentially, but in parallel. Drawing tools from Machine Learning and Automatic Speech Recognition, we construct a model of this early process, test it on 2 large spontaneous speech databases (Japanese, French and Dutch) and test its predictions in infants using behavioral, EEGs and fNIRS techniques. 1. Coding. We study different ways of defining coding features for speech, from fine-grained to coarse grained, in view of the automatic discovery of a hierarchy of linguistic units. We compare this with a systematic study of the units of speech coding as they unfold in 6, 9 and 12 month old infants.. 2. Lexicon. Infants recognize some words before they know the phonemes of their language; we modify existing word segmentation algorithms so they can work on raw speech. We test the unique prediction that infants start with a large lexicon that’s quite different from the adult one. 3. Rules. Phonemes are produced as overlapping, coarticulated gestures. To untangle these context effects, we use a predictive model of coarticulation in auditory space and invert it. We test when and how infants perform reverse coarticulation. 4. Integration. The above subprojects provide only an initial bootstrapping into approximate phonemes, words, and contextual rules. We show how to iteratively integrate these approximate representations to derive better ones. The outcome will be numerically assessed on an adult directed and infant directed speech database, and compared to those of to state-of-the-art supervized phoneme recognizers. The predictions will be tested in infants learning artificial languages and in a longitudinal study."

2 194 557 €

Start date: 2012-11-01, End date: 2017-10-31

Subjectivity defines the subject who is perceiving, feeling, thinking, acting, and is essential to understand the conscious mind from the inside. However, subjectivity, or non-reflective first-person perspective, is not identified as a core concept in cognitive neuroscience and its neural basis remain largely unknown. BRAVIUS offers a unified framework to appraise both the concept and the neural mechanisms generating subjectivity. The hypothesis relies on two vital organs that generate their own rhythmic electrical activity, the stomach and the heart, and therefore constantly send information up to the neocortex, even in the absence of bodily change. Cortical responses to those visceral organs would define the organism as an entity at the neural level, and create a subject-centered referential from which first-person perspective can develop. In other words, the cardiac and gastric pacemakers could feed the brain with self-specifying inputs. BRAVIUS builds on previous theories and studies on visceral states but focuses on ascending information, from viscera to brain, and does not require visceral states to change nor to be consciously perceived. Experimentally, BRAVIUS measures the understudied neural response evoked by heartbeats and introduces a new measure, the electrogastrogram, to quantify the slow gastric pacemaker. BRAVIUS will test with magneto-encephalography (MEG) the role of neural responses to ascending visceral signals in generating subjectivity by cutting across domains of cognitive sciences and exploring diverse paradigms where subjectivity is engaged: perceptual consciousness, self-consciousness, emotions and decision making. BRAVIUS will further explore how cardiac and gastric ascending signals shape the temporal (MEG) and spatial (fMRI) organization of spontaneous brain activity. The project outcome is a detailed mechanistic neural account of the most private part of the human mind, and a unified concept of subjectivity across cognitive domains.

2 080 000 €

Start date: 2015-12-01, End date: 2020-11-30

For over half a millennium, the great medieval capital of Angkor lay at the heart of a vast empire stretching across much of mainland SE Asia. Recent research has revealed that the famous monuments of Angkor were merely the epicentre of an immense settlement complex, with highly elaborate engineering works designed to manage water and mitigate the uncertainty of monsoon rains. Compelling evidence is now emerging that other temple complexes of the medieval Khmer Empire may also have formed the urban cores of dispersed, low-density settlements with similar systems of hydraulic engineering. Using innovative airborne laser scanning (‘lidar’) technology, CALI will uncover, map and compare archaeological landscapes around all the major temple complexes of Cambodia, with a view to understanding what role these complex and vulnerable water management schemes played in the growth and decline of early civilisations in SE Asia. CALI will evaluate the hypothesis that the Khmer civilisation, in a bid to overcome the inherent constraints of a monsoon environment, became locked into rigid and inflexible traditions of urban development and large-scale hydraulic engineering that constrained their ability to adapt to rapidly-changing social, political and environmental circumstances. By integrating data and techniques from fast-developing archaeological sciences like remote sensing, palaeoclimatology and geoinformatics, this work will provide important insights into the reasons for the collapse of inland agrarian empires in the middle of the second millennium AD, a transition that marks the emergence of modern mainland SE Asia. The lidar data will provide a comprehensive and internally-consistent archive of urban form at a regional scale, and offer a unique experimental space for evaluating socio-ecological resilience, persistence and transformation over two thousand years of human history, with clear implications for our understanding of contemporary urbanism and of urban futures.

1 482 844 €

Start date: 2015-03-01, End date: 2020-02-29

The generation of animals by nuclear transfer demonstrated that the epigenetic state of somatic cells could be reset to an embryonic state, capable of directing the development of a new organism. The nuclear cloning technology is of interest for transplantation medicine, but any application is hampered by the inefficiency and ethical problems. A breakthrough solving these issues has been the in vitro derivation of reprogrammed Induced Pluripotent Stem “iPS” cells by the ectopic expression of defined transcription factors in somatic cells. iPS cells recapitulate all defining features of embryo-derived pluripotent stem cells, including the ability to differentiate into all somatic cell types. Further, recent publications have demonstrated the ability to directly trans-differentiate somatic cell types by ectopic expression of lineage specification factors. Thus, it is becoming increasingly clear that an ultimate goal in the stem cell field is to enable scientists to have the power to safely manipulate somatic cells by “reprogramming” their behavior at will. However, to frame this challenge, we must understand the basic mechanisms underlying the generation of reprogrammed cells in parallel to designing strategies for their medical application and their use in human disease specific research. In this ERC Starting Grant proposal, I describe comprehensive lines of experimentation that I plan to conduct in my new lab scheduled to open in April 2011 at the Weizmann Institute of Science. We will utilize exacting transgenic mammalian models and high throughput sequencing and genomic screening tools for in depth characterization of the molecular “rules” of rewiring the epigenome of somatic and pluripotent cell states. The proposed research endeavors will not only contribute to the development of safer strategies for cell reprogramming, but will also help decipher how diverse gene expression programs lead to cellular specification during normal development.

1 960 000 €

Start date: 2011-11-01, End date: 2016-10-31

Understanding how values of different options that lead to choice are represented in the brain is a basic scientific question with far reaching implications. I recently showed that by the mere-association of a cue and a button press we could influence preferences of snack food items up to two months following a single training session lasting less than an hour. This novel behavioural change manipulation cannot be explained by any of the current learning theories, as external reinforcement was not used in the process, nor was the context of the decision changed. Current choice theories focus on goal directed behaviours where the value of the outcome guides choice, versus habit-based behaviours where an action is repeated up to the point that the value of the outcome no longer guides choice. However, in this novel task training via the involvement of low-level visual, auditory and motor mechanisms influenced high-level choice behaviour. Thus, the far-reaching goal of this project is to study the mechanism, by which low-level sensory, perceptual and motor neural processes underlie value representation and change in the human brain even in the absence of external reinforcement. I will use behavioural, eye-gaze and functional MRI experiments to test how low-level features influence the neural representation of value. I will then test how they interact with the known striatal representation of reinforced behavioural change, which has been the main focus of research thus far. Finally, I will address the basic question of dynamic neural plasticity and if neural signatures during training predict long term success of sustained behavioural change. This research aims at a paradigmatic shift in the field of learning and decision-making, leading to the development of novel interventions with potential societal impact of helping those suffering from health-injuring behaviours such as addictions, eating or mood disorders, all in need of a long lasting behavioural change.

1 500 000 €

Start date: 2017-01-01, End date: 2021-12-31

All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.

1 499 125 €

Start date: 2018-01-01, End date: 2022-12-31

This project will analyse historical change in the Mediterranean over the long run. It challenges totalising narratives aiming to “europeanise” Mediterranean history as having led somewhat naturally to European domination in the 19th and 20th centuries. Instead of the one-sided view of institutional and territorial integration as a consequence of the mere diffusion of European institutional models and legal codifications linked to a supposed lex mercatoria rediviva or law merchant in force in all countries and at all times, the specific approach of this project consists in combining concrete local, regional and thematic approaches with a focus on trade as the most widely accepted interaction even in times of sharp conflict, and on commercial and maritime litigation as an indicator for the intensity and changing modes of intercultural exchange. In an actor-centred perspective, we will take into account a variety of individual and institutional actors involved in trade. Their interaction was based on a combination of shared customs, local usages and legal traditions. Addressing competing instances and drawing on different legal resources, they contributed to a reconfiguration of the legal and institutional landscape. These issues will be investigated through the comparative analysis of commercial litigation and conciliation concerning trade in Mediterranean port cities, with a focus on disputes involving litigants who were not subjects of the local authorities, or whose legal status was linked to their religious identity. The encounters of Muslim, Jewish, Armenian, Protestant merchants and sailors with different legal customs and judicial practices appear as the social sites of legal and cultural creativity. Through the prism of commercial litigation, we will thus achieve a more precise and deeper understanding of the practices of intercultural trade, in a context profoundly shaped by legal pluralism and multiple and overlapping spaces of jurisdiction.

2 484 000 €

Start date: 2012-09-01, End date: 2018-06-30

With COVOPRIM I propose to reconstruct the recent evolutionary history of one often overlooked component of speech and language: voice perception. Perceptual and neural mechanisms of voice perception will be compared between humans, macaques and marmosets –two highly vocal and extensively studied monkey species–to quantify cross-species differences and infer mechanisms potentially inherited from a common ancestor. Two key building blocks of vocal communication detailed in my past research in humans will be compared across species: (1) the sensitivity to conspecific vocalizations, and (2) the processing of speaker/caller identity. COVOPRIM is organized in three workpackages (WPs). WP1 will use large-scale behavioural testing based on ad-lib access of monkeys to automated test systems (following the highly successful model developed locally with baboons). Two main behavioural experiments will establish psychometric response functions for robust cross-species comparison. WP2 will use functional magnetic resonance imaging (fMRI) to measure cerebral activity during auditory stimulation in the three species. I will compare across brains the organization of what I hypothesize constitutes a “voice patch system” similar to the face patch system of visual cortex and broadly conserved in primates. I will also take advantage of the monkey models and use long-term, subject-specific enrichments of the auditory stimulation to probe the experience-dependence of neural coding in the voice patch system—an outstanding issue in human voice perception. WP3 will use fMRI-guided microstimulation in monkeys and transcranial magnetic stimulation in humans to establish the effective connectivity within the voice patch system and test the causal relation between voice patch neuronal activity and voice perception behaviour. COVOPRIM is expected to generate considerable advances in our understanding of the recent evolution in primates of the perceptual and neural mechanisms of voice perception.

2 900 000 €

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

Adaptive behaviour is typically attributed to an executive-control system that allows people to regulate impulsive actions and to fulfil long-term goals instead. Failures to regulate impulsive actions have been associated with a variety of clinical and behavioural disorders. Therefore, establishing a good understanding of impulse-control mechanisms and how to improve them could be hugely beneficial for both individuals and society at large. Yet many fundamental questions remain unanswered. This stems from a narrow focus on reactive inhibitory control and well-practiced actions. To make significant progress, we need to develop new models that integrate different aspects of impulsive action and executive control. The proposed research program aims to answer five fundamental questions. (1) Can novel impulsive actions arise during task-preparation stages?; (2) What is the role of negative emotions in the origin and control of impulsive actions?; (3) How does learning modulate impulsive behaviour?; (4) When are impulsive actions (dys)functional?; and (5) How is variation in state impulsivity associated with trait impulsivity? To answer these questions, we will use carefully designed behavioural paradigms, cognitive neuroscience techniques (TMS & EEG), physiological measures (e.g. facial EMG), and mathematical modelling of decision-making to specify the origin and control of impulsive actions. Our ultimate goal is to transform the impulsive action field by replacing the currently dominant ‘inhibitory control’ models of impulsive action with detailed multifaceted models that can explain impulsivity and control across time and space. Developing a new behavioural model of impulsive action will also contribute to a better understanding of the causes of individual differences in impulsivity and the many disorders associated with impulse-control deficits.

1 998 438 €

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

This project aims to explore the effects of human settlement intensity on desert ecological community structure, focusing on the hitherto unstudied phenomenon of trophic cascades in antiquity. Its key research question is whether human-induced changes in arid land biodiversity can feedback to affect natural resources important for human subsistence, such as pasture and wood. The role of such feedback effects in ecological systems is increasingly acknowledged in recent years in the biological literature but has not been addressed in the study of human past. The research question will be approached using bioarchaeological methods applied to the uniquely-preserved material record from the middle and late Holocene settlement sequence (approximately 4,500 BCE to 700 CE) of the Dead Sea Ein Gedi Oasis, and to the contemporary palaeontological assemblages from caves located in the surrounding Judean Desert. The proposed research is expected to bridge between aspects of current thinking on ecosystem dynamics and the study of human past by exploring the role of trophic cascades as an invisible dimension of Anthropocene life in marginal environments. The study of the history of human impact on such environments is important to resource management planning across a rapidly expanding ecological frontier on Earth, as climate deterioration brings more people in contact with life-sustaining and sensitive arid land ecosystems.

1 499 563 €

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

The switch from parchment to paper had a fundamental impact on later medieval universities, equivalent to the shift to Open Access today, hindering some intellectual practices while encouraging others. The DEBATE project identifies a neglected genre of latin texts that flourished on paper, the Principia, which record the public confrontations between candidates (socii) for the title of doctor. These debates, imposed by university statutes throughout Europe as annual exercises linked to lectures on the Sentences (the medieval parallel to our PhD thesis), forced the candidate to reveal his innovative theories (sheets of papers were exchanged among the socii beforehand), display his erudition and prove his intellectual prowess before a large audience. The futuristic discussion usually exceeded the confines of one discipline and allowed the bachelor to indulge his interdisciplinary interests, employing science, theology, mathematics, politics, literature, and rhetoric in his polemics against his colleagues. Principia thus reveal the cutting edge method of fostering science in later medieval universities. The DEBATE team intends to identify new manuscripts, edit the texts, establish authorship for anonymous fragments and propose an interpretation that will help explain how innovation was a primordial target in medieval academia. Putting together all the surviving texts of Principia produced in various cultural contexts, this project will provide a wealth of material that will bring about a basic change in our understanding of the mechanism of the production of academic knowledge in the early universities all around Europe.The project is designed to promote erudition by combining a palaeographical, codicological, editorial and hermeneutical approach, aiming to open an advanced area of inquiry focusing on an intellectual practice that bound together medieval universities from different geographical and cultural regions: Paris, Bologna, Vienna, Prague, Krakow and Cologne.

1 997 976 €

Start date: 2018-08-01, End date: 2023-07-31

The communities of the Western Sephardic Diaspora were founded in the 16th and 17th centuries by New Christians from Iberia who returned to Judaism that had been abandoned by their ancestors in the late Middle Ages. This project will concentrate on the changes in the religious conceptions and behavior as well as the cultural patterns of the communities of Amsterdam, Hamburg, Leghorn, London, and Bordeaux. We will analyze the vigorous activity of their leaders to set the boundaries of their new religious identity in comparison to the policy of several Christian “communities of belief,” which went into exile following religious persecution in their homelands. We will also examine the changes in the attitude toward Judaism during the 17th century in certain segments of the Sephardic Diaspora: rather than a normative system covering every area of life, Judaism came to be seen as a system of faith restricted to the religious sphere. We will seek to explain the extent to which this significant change influenced their institutions and social behaviour. This study will provide us with better understanding of the place of the Jews in European society. At the same time, we will subject a central series of concepts in the historiographical discourse of the Early Modern Period to critical analysis: confessionalization, disciplinary revolution, civilizing process, affective individualism, etc. This phase of the research will be based on qualitative and quantitative analysis of many hundreds of documents, texts and the material remains of these communities. Using sociological and anthropological models, we will analyze ceremonies and rituals described at length in the sources, the social and cultural meaning of the architecture of the Sephardic synagogues of that time, and of other visual symbols.

1 671 200 €

Start date: 2012-03-01, End date: 2018-02-28

Every year a brain stroke will impair approximately 2 million Europeans. Notwithstanding recent progress, many of these individuals will have persistent cognitive deficits, impacting their personality, degrading their quality of life and preventing their return to work. Early identification of anatomical predictors of brain recovery may significantly reduce the burden of these deficits on patients, their families and wider society, while also leading to the discovery of new targets for treatments. I have pioneered the development of imaging techniques that allow for the exploration of the relationship between brain disconnection and neuropsychological syndromes. With these tools, I aim to demonstrate that the structural organisation of the human brain's connections is the common denominator supporting functional specialisation and, when damaged, neuropsychological disorders. Building on my expertise, I plan to (1) establish an atlas mapping the function of white matter for the entire human brain, (2) fractionate the stroke population according to disconnection profiles, (3) predict neuropsychological symptoms based on disconnection profiles, and (4) characterise and manipulate the fine biology involved in the disconnection recovery.In so doing, this project will introduce a paradigm shift in the relationship between brain structure, function and behavioural/cognitive disorders. I will deliver a comprehensive biological model of the neurocircuitry that supports neuropsychological syndromes, which will gather the modular organisation of primary idiotypic functions with the integrative organisation of highly associative levels of functions. In the long term, this project will allow me to determine if measures of brain ‘connectivity’ can be translated into advanced standard procedures that provide for a more personalised medicine, that focuses upon rehabilitation and improving the prediction of symptom recovery, while providing new targets for pharmacological treatment.

1 999 201 €

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

Oriented cell divisions dictate morphogenesis by shaping tissues and organs of multicellular organisms. Oriented cell divisions have profound influence in plants because their cell positions are locked by shared cell walls. A relay of cell divisions involving precise division plane switches determines embryonic body plan, organ layout and organ architecture in plants. Cell division planes in plants are specified by reorganization of premitotic cortical microtubule array and how this occurs is a long-standing key question. My recent results establish, for the first time in plants, an in vivo inducible and traceable, precise 90º cell division plane switch system. With this system I identified a pathway that proceeds from transcriptional activation through a signaling module all the way to the activation of microtubule regulators that orchestrate switches in premitotic microtubule organization and cell division planes. My findings provide a first paradigm in plants of how genetic circuitry patterns cell division planes via feeding onto cellular machinery and pave the way for unraveling mechanistic control of cell division plane switch. By establishing a precise cell division plane switch system I am in a unique position to answer: 1. What transcriptional program and molecular players control premitotic microtubule reorganization? 2. Which mechanisms switch premitotic microtubule array? 3. What influence do identified players and mechanisms have on different types of oriented cell divisions in plants? For this I propose a systematic research plan combining (i) forward genetics and expression profile screens for identifying a suite of microtubule regulators, (ii) state-of-the-art microscopy and modeling approaches for uncovering mechanisms of their actions and (iii) their tissue-specific manipulations to modify plant form. By unraveling players and mechanisms this proposal shall resolve regulation of oriented cell divisions and expand plant engineering toolbox.

1 500 000 €

Start date: 2013-01-01, End date: 2017-12-31

DREAM, Drafting and Enacting the Revolutions in the Arab Mediterranean, seeks to write the history of the revolutions in the Arab Mediterranean since the independences. It aims to write a transnational history of often forgotten struggles, recall facts and original forms of resistance. We know very few about the revolts that occurred in this period, and even less about the memory that they left in the societies, the way these memories circulated. This rediscovery of revolutions in the shadows must be done through the collection of original material, specifically “poor archives” of the ordinary and the production of Archives – through a combination of classical interviews and innovative methods that involve researchers, archivists, artists and the actors themselves. The objective is to write a history that focuses on emotions and paths of revolts, telling us more about the link between all dimensions of human lives in these territories (religion, gender, social positions) and the articulation of these dimensions in the revolutionary projects. DREAM aims to write a history that doesn’t produce heroes or big figures, doesn’t discuss success or failure, but tries to understand the motivations and the potentialities that were at stake in different episodes and moments, during the uprisings and in between them. It aims to explore the historical signification and the concrete aspects of the call for dignity (Karama/sharaf) in a space that, after liberating itself from the colonial domination, was trapped into the illusion of a common faith (being it the Arab nation or the Islamic umma) and the concrete oppression of authoritarian regimes. This period needs urgently to be explored and history, with its modern tools and patterns, can embrace and trace the particular conditions in which Arab people lived for more than six decades, and specifically the frames of their dreams and projections.

1 941 050 €

Start date: 2018-09-01, End date: 2023-08-31

Membrane fusion is a universal process essential inside cells (endoplasmic) and between cells in fertilization and organ formation (exoplasmic). With the exception of SNARE-mediated endoplasmic fusion the proteins that mediate cellular fusion (fusogens) are unknown. Despite many years of research, little is known about the mechanism of cell-cell fusion. Our studies of developmental cell fusion in the nematode C. elegans have led to the discovery of the first family of eukaryotic fusogens (FF). These fusogens, EFF-1 and AFF-1, are type I membrane glycoproteins that are essential for cell fusion and can fuse cells when ectopically expressed on the membranes of C. elegans and heterologous cells. Our main goals are: (1) To determine the physicochemical mechanism of cell membrane fusion mediated by FF proteins. (2) To find the missing fusogens that act in cell fusion events across all kingdoms of life. We hypothesize that FF proteins fuse membranes by a mechanism analogous to viral or endoplasmic fusogens and that unidentified fusogens fuse cells following the same principles as FF proteins. Our specific aims are: AIM 1 Determine the mechanism of FF-mediated cell fusion: A paradigm for cell membrane fusion AIM 2 Find the sperm-egg fusion proteins (fusogens) in C. elegans AIM 3 Identify the myoblast fusogens in mammals AIM 4 Test fusogens using functional cell fusion assays in heterologous systems Identifying critical domains required for FF fusion, intermediates in membrane remodeling, and atomic structures of FF proteins will advance the fundamental understanding of the mechanisms of eukaryotic cell fusion. We propose to find the Holy Grail of fertilization and mammalian myoblast fusion. We estimate that this project, if successful, will bring a breakthrough to the sperm-egg and muscle fusion fields with potential applications in basic and applied biomedical sciences.

2 380 000 €

Start date: 2011-05-01, End date: 2016-04-30

Intractable conflicts are one of the gravest challenges to both humanity and science. These conflicts are initiated and perpetuated by people; therefore changing people's hearts and minds constitutes a huge step towards resolution. Research on emotions in conflicts has led to the realization that intergroup emotions are critical to conflict dynamics. This project’s intrinsic question is whether and how intergroup emotions can be regulated to alter attitudes and behavior towards peace. I offer an innovative path, using two strategies of emotion regulation. The first is Direct Emotion Regulation, where traditional, effective emotion regulation strategies can be used to change intergroup emotional experiences and subsequently political positions in conflict situations. The second, Indirect Emotion Regulation, serves to implicitly alter concrete cognitive appraisals, thus changing attitudes by changing discrete emotions. This is the first attempt ever to integrate psychological aggregated knowledge on emotion regulation with conflict resolution. I propose 16 studies, conducted in the context of the intractable Israeli-Palestinian conflict. Seven studies will focus on direct emotion regulation, reducing intergroup anger and hatred, while 9 studies will focus on indirect regulation, aspiring to reduce fear and despair. In both paths, correlational and in-lab experimental studies will be used to refine adequate strategies of down regulating destructive emotions, the results of which will be used to develop innovative, theory-driven education and media interventions that will be tested utilizing wide scale experience sampling methodology. This project aspires to bridge the gap between basic and applied science, creating a pioneering, interdisciplinary framework which contributes to existing knowledge on emotion regulation in conflict and implements ways to apply it in real-world circumstances.

1 499 344 €

Start date: 2014-02-01, End date: 2019-01-31

Contrary to previous beliefs, recent studies have suggested that apoptotic cells play an important dynamic role during morphogenesis. Nonetheless, the mechanisms whereby dying cells drive tissue shape modification remain elusive. Using the Drosophila developing leg as a model system to study apoptosis-dependent epithelium folding, we have recently shown that apoptotic cells produce a pulling force through the unexpected maintenance of their adherens junctions that serves as an anchor to an apico-basal Myosin II cable. The resulting apoptotic apico-basal force leads to a non-autonomous increase in tissue tension and apical constriction of surrounding cells, leading to epithelium folding. These results reveal that, far from being passively eliminated as generally thought, dying cells are very active until the end of the apoptotic process. The objective of the present proposal is to understand how apoptotic cells influence their surroundings from the micro-environment to the macro-scale level. Our first aim is to dissect the cellular mechanisms governing the generation of the apoptotic force and its transmission to the tissue, both apically through planar polarity and basally through the extra-cellular matrix (ECM), in parallel with the identification of the network of genes orchestrating apoptosis-dependent morphogenesis through a powerful genetic screen. Interesting preliminary results have already identified the epithelio-mesenchymal-transition gene Snail as essential for the progression of apoptosis, thus validating our approach. Therefore, the second aim of this project is to compare Snail function in the control of adhesion and ECM dynamics and in the generation of tissue tension in both EMT and apoptosis. This original comparative study should bring novel insight into these two fundamental processes. To perform this work, we will use elegant genetic tools combined to state-of-the-art live imaging techniques, together with robust biophysical modelling.

2 311 844 €

Start date: 2015-09-01, End date: 2020-08-31

The endoplasmic reticulum (ER) is the cellular organelle that serves as the entry site into the secretory pathway. Although the ER has a single continuous membrane, it is functionally divided into subdomains (SDs). These specialized regions allow the ER to carry out a multitude of functions such as folding, maturation, quality control and export, of all secreted and most membrane bound proteins; lipid biosynthesis; ion homeostasis; and communication with all other organelles. The ER is therefore not only the largest single copy organelle in most eukaryotic cells, but, thanks to the presence of SDs, also one of the more functionally diverse and structurally complex. Changes in ER functions have been shown to contribute to the progression of many diseases such as heart disease, neurodegeneration and diabetes. Moreover, a robustly functioning ER is required for development of dedicated secretory cells such as antibody producing plasma cells and insulin secreting pancreatic cells. The past years have brought about a revolution in our understanding of basic ER functions and the homeostatic responses coordinating them. However, despite their obvious importance for robust activity of the ER, we still know very little about SD biogenesis and function. Therefore, the time is now ripe to extend our understanding by facing the next challenges in the field. Specifically, it is now of major importance to understand how cells ensure accurate SD biogenesis and function. This proposal tackles this question by three independent but complementary screens each aimed at revealing one aspect of SDs: their structure/function, biogenesis or dynamics. The merging of all three aspects of information will give us a holistic picture of this process – one that could not have been attained by the pixilated view of any single piece of data. We propose to explore these facets in both yeast and mammals utilizing systematic tools such as high content microscopic screens followed up by the creation of genetic interaction maps and follow-up hypothesis based biochemical and genetic experiments. By combining several approaches and different organisms we hope to enable a more efficient reconstruction of this complex process. When completed this proposal will have shed light on a little explored but central question in cellular biology. More broadly, the mechanisms that arise as guiding SD biogenesis may help us in understanding how membrane domains form in general. Due to the novelty of our approach and the cutting-edge tools used to tackle this fundamental problem in cell biology, this work will provide a paradigm for addressing complex biological questions in eukaryotic cells. It may very well be that it is this aspect of the proposal that may ultimately most broadly impact the biological community.

1 499 999 €

Start date: 2010-09-01, End date: 2015-08-31

"Palaeolithic stone tool hafting has been considered important for decades, both in terms of technological and cognitive evolutions, but it has been hard to design methods that allow detailed insight into the appearance of hafting and its evolution through time. The main reason is that handles were manufactured from organic materials and these are only rarely preserved. The issue thus appears to largely escapes us, but as finds become more and more numerous, promising new techniques have also been developed, which allow a more detailed investigation of hafting. It has been demonstrated that a microscopic investigation of stone tools allows a distinction between tools that were used in the hand and those that were mounted in / on a handle, as well as an interpretation of the hafting arrangement. Knowing whether and how stone tools were hafted provides crucial data for improving our understanding of past human behaviour. It is invaluable for a better comprehension of technological evolutions, it provides insight into the organic tool component that is rarely preserved, and it allows understanding the complete life cycle of stone tools. The goal of this research project is to gain insights in the appearance, regional and chronological variability, and evolution of Palaeolithic stone tool hafting in Europe and the remaining Old World through a comprehensive functional investigation of key sites, which includes the analysis of wear traces and residues, bio/physico-chemical analyses, next to an elaborate experimental program. The proposed project starts from the conviction that many of the changes observed during the Palaeolithic can be understood based on functional data. Consequently, this research project will contribute significantly to our understanding of archaeological assemblages and their variability, and of past human behaviour and its evolution through time."

1 192 300 €

Start date: 2013-01-01, End date: 2017-12-31

Face recognition is one of the most complex functions of the human mind/brain, so that no artificial device can surpass human abilities in this function. The goal of this project is to understand a fundamental aspect of face recognition, individual face perception: how, from sensory information, does the human mind/brain build a visual representation of a particular face? To clarify this question, I will introduce the method of steady-state visual evoked potentials (SSVEPs) in the field of face perception. This approach has never been applied to face perception, but we recently started using it and collected strong data demonstrating the feasibility of the approach. It is based on the repetitive stimulation of the visual system at a fixed frequency rate, and the recording on the human scalp of an electrical response (electroencephalogram, EEG) that oscillates at that specific frequency rate. Because of its extremely high signal-to-noise ratio and its non-ambiguity with respect to the measurement of the signal of interest, this method is ideal to assess the human brain’s sensitivity to facial identity, non-invasively, and with the exact same approach in normal adults, infants and children, as well as clinical populations. SSVEP will also allow “tagging” different features of a stimulus with different stimulation frequencies (“frequency-tagging” method), and thus measure the representation and processing of these features independently, as well as their potential integration. Overall, this proposal should shed light on understanding one of the most complex function of the human mind/brain, while its realization will undoubtedly generate relevant data and paradigms useful for understanding other aspects of face processing (e.g., perception of facial expression) and high-level visual perception processes in general.

1 490 360 €

Start date: 2012-02-01, End date: 2017-01-31

Higher animals employ a complex muscle network for their daily movements. Proper execution of movements requires individual muscles to form at the correct positions, connect to proper tendons and produce sufficient force. Muscle development is a multi-step process: myoblasts proliferate, migrate to particular locations and fuse to myotubes. Myotubes target appropriate tendons to establish a stable connection and transition to myofibers by assembling their specific contractile apparatus in a process called myofibrillogenesis. Interestingly, Drosophila adult muscles consist of two major types: tubular striated muscles, e.g. present in legs for walking, and fibrillar flight muscles that power rapid wing oscillations required during flight. The aims of my ERC proposal will address: 1) How do transcriptional networks instruct muscle diversity? 2) Which proteins have an essential role in myofibrillogenesis in different muscle types? 3) How are myofibrils and sarcomeres built in space and time in a muscle specific manner? My entry point is a genome-wide muscle-specific RNAi screen that identified the transcription factor Salm as selector gene for fibrillar flight muscle. Salm alone is sufficient to instruct all specific properties of fibrillar muscle. We will apply a combination of next-generation mRNA sequencing and chromatin immunoprecipitation to dissect the mechanism how Salm initiates myofiber type specification. We will manipulate the identified differentially expressed individual components to assess their mechanistic role in the differential assembly of myofibrils. Detailed in vivo time-lapse analysis of wild-type and mutant muscle combined with biochemical purifications of protein complexes will lead us to a better understanding of the dynamics and molecular constraints of sarcomere formation in each muscle type. Together, this will unravel developmental principles instructing muscle morphogenesis that are conserved to vertebrates and thus are of general interest.

1 496 000 €

Start date: 2013-02-01, End date: 2019-01-31

The role of children's behavior and temperament is increasingly acknowledged in family research. Gene-environment Correlation (rGE) processes may account for some child effects, as parents react to children s behavior which is in part genetically influenced (evocative rGE). In addition, passive rGE, in which parenting and children s behavior are correlated through overlapping genetic influences on family members behavior may account in part for the parenting-child behavior relationships. The proposed project will be the first one to directly address these issues with DNA information on family members and quality observational data on parent and child behaviors, following children through early development. Two separate longitudinal studies will investigate the paths from children s genes to their behavior, to the way parents react and modify their parenting towards the child, affecting child development: Study 1 will follow first-time parents from pregnancy through children s early childhood, decoupling parent effect and child effects. Study 2 will follow dizygotic twins and their parents through middle childhood, capitalizing on genetic differences between twins reared by the same parents. We will test the hypothesis that parents' characteristics, such as parenting style and parental attitudes, are associated with children's genetic tendencies. Both parenting and child behaviors will be monitored consecutively, to investigate the co-development of parents and children in an evocative rGE process. Child and parent candidate genes relevant to social behavior, notably those from the dompaminergic and serotonergic systems, will be linked to parents behaviors. Pilot results show children s genes predict parenting, and an important task for the study will be to identify mediators of this effect, such as children s temperament. We will lay the ground for further research into the complexity of gene-environment correlations as children and parents co-develop.

1 443 687 €

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

The contribution of clathrin-independent endocytosis to the cellular entry of signaling receptors, cell adhesion factors, and other cell surface molecules is well documented. However, how this process is initiated is still unknown. We have recently found that a cellular lectin, galectin-3 (Gal3), entered cells via morphologically distinct tubular structures, so-called clathrin-independent carriers (CLICs); Gal3 endocytosis was required for the uptake of the CLIC cargo CD44, a cell adhesion/migration factor; CD44 and Gal3 uptake required glycosphingolipids (GSLs); Gal3 induced tubular membrane invaginations in a GSL-dependent manner. Based on these findings we propose the groundbreaking hypothesis that Gal3 is an adaptor that clusters cargo proteins carrying defined carbohydrate modifications together with specific GSLs into nanoscale membrane environments whose mechanical properties drive the clathrin-independent formation of endocytic pits. In this program, we will first establish the compositional topology of endocytic galectin processes (Aim 1). The adaptor hypothesis will then be tested using innovative chemical biology tools (Aim 2). Quantitative models of cargo clustering and membrane shape changes will be developed on the basis of biophysical measurements and coarse grain simulations (Aim 3). Intravital imaging of endocytosis and cell migration in mice will finally explore how the functional link between galectins and GSLs contributes to wound healing in the colon (Aim 4). The molecular functions of galectins and GSLs in endocytosis — major unresolved questions in cellular membrane biology — will thereby be established, providing details from atomic arrangements via multi-molecular complexes and meso-scaled membrane domains to in vivo physiology. I am confident that this program will lead to the discovery of a new clathrin-independent endocytic mechanism by which different types of cargo are sorted to and internalized from specific membrane domains.

2 270 054 €

Start date: 2014-04-01, End date: 2019-03-31

The aim of GESHAEM is to investigate economy, fiscality and territorial management in the most important agricultural region of Egypt, the Fayyum, in the first century of the Greek domination (3rd century BCE). For this purpose, a large corpus of administrative and fiscal papyri discovered in Egyptian mummies will be studied: the unpublished Greek and Egyptian papyri of the Jouguet collection of the Sorbonne. Coming from bilingual archives, these documents will change our view of the early Ptolemaic kingdom in the third century BCE. The history of this Hellenistic kingdom has long been described as the history of a Greek kingdom. Recently, however, the native Egyptian contribution in the building of this kingdom has come to the fore: the Ptolemaic administration was in large part made up of people of Egyptian origin who spoke and wrote both Greek and Egyptian, continuing a millennia-old administrative tradition adapted to the new regime. The Jouguet papyri open new perspectives because, unlike most demotic documents of the Graeco-Roman period, these were not written inside temples but for the civil government. Like the Greek ones they are concerned with the agricultural administration of the Fayyum region. The Jouguet texts were written on second-hand papyrus reused to make mummy casing called cartonnage. Most of these decorated mummy cartonnages were destroyed immediately after their discovery at the beginning of the 20th century, but around twenty remain in part of the Jouguet collection that has not yet been inventoried. The extraction of new papyri from the remaining cartonnages will be achieved without destroying the objects themselves, which will be restored and, for the first time, studied in their own right. Thus GESHAEM intends to bring new data both for historians working on the ancient economy and fiscality, as well as for art historians.

1 498 368 €

Start date: 2018-02-01, End date: 2023-01-31

The production of raw glass up until the early medieval period was restricted to few primary glassmaking centres in the Levant and Egypt producing glasses with distinct chemical fingerprints that were then shipped all over the Mediterranean. The study of glass thus provides a unique perspective on long-distance communications and shifts in economy, trade and cultural interactions. This project explores the production, trade and consumption of glass as a major economic activity in the medieval Mediterranean. The chronological parameters are the 4th to 12th centuries CE, covering a period of significant diversification and technological innovations in glass production. The project addresses three broad gaps in our understanding of these developments: Byzantine glassmaking; the spread of Islamic plant ash glass; and the role of the Iberian peninsula. GlassRoutes will push the frontiers of glass research by integrating chemical, archaeological and documentary data about these three key players in the medieval glass economy. By comparing the material and artistic aspects of glass assemblages from selected Mediterranean sites it will identify patterns in the manufacture, trade and usage of glass. The aim of GlassRoutes is to establish the socio-cultural and geopolitical dimensions of glass. What types of primary (raw) glass are found at different sites? How do they compare in terms of secondary use (types of artefacts)? What are the reasons for the differential use of glass and its colours? Research will examine the provenance of the material in relation to its use for selected artefacts to reveal the economic and cultural mechanisms underlying the culture-specific use of glass. This project is unique in its interdisciplinary approach; it combines archaeological, historical and analytical data as well as statistic tools to characterise the dynamic relationship between supply and consumption and its implications for artistic practices and technological innovation.

1 982 401 €

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

Animal growth is a complex process that is intimately linked to the developmental program in order to form fit adults with proper size and proportions. Genetics is an important determinant of growth, exemplified by the role of local diffusible molecules in setting organ proportions for a given species. In addition to this genetic control, organisms use adaptation mechanisms allowing modulating the size of individuals according to environmental cues, among which nutrition. Therefore, sophisticated cross-talks between local and global cues are at play for the determination of the final size of an individual. The major objective of this project is to tackle the mechanisms involved in coupling growth control with environmental cues, as well as the mechanisms participating in growth arrest and the determination of final size. Our project proposes a blend of physiological and genetic approaches on the Drosophila model, with the use of tissue-targeted loss-of-function to unravel some of the important cross-talks existing between organs for the control of growth at the global level. We will develop these approaches to (i) unravel the molecular nature of tissue cross-talks involved in nutrient sensing and the control of insulin/IGF secretion; (ii) tackle the feed-back mechanisms linking the developmental clock to the growing state of tissues and organs. These projects should bring new contributions in two separate fields related to growth control, Developmental Biology and Physiology, in an attempt to merge these complementary approaches into a broader vision of this fascinating biological question.

2 500 000 €

Start date: 2011-07-01, End date: 2016-06-30

The scientific research project submitted to the ERC intends to examine the creation of the French political science lexicon from a linguistic point of view. Most of the Political science vocabulary that the French language uses today comes from the translations from Latin and Greek into French during the 14th and 15th centuries. Historians and philosophers have noticed that the 14th century is an essential period for neologisms in the political science field. But no scientific research has been yet conducted to prove it, especially because of the lack of modern editions of the texts. The scientific project submitted to the ERC can be developed in three parts during the next 5 academic years: 1/ an edition of a major political science masterpiece in Middle French from the 14th century that has never been published before (years 1 to 5) : The City of God written by Augustine and translated by Raoul de Presles. The modern edition of the first translation of the City of God will allow researchers to have an easy access to primary sources in order to lead new research in linguistics, history, political sciences, and more generally in Humanities. 2/ a publication of a scientific monograph on the French political science lexicon (year 4). Indeed, such a scientific monograph will give a panoramic overview of the French Political Science Lexicon and will allow researchers to better understand the history of French concepts in Humanities. 3/ a publication of a Dictionary of Political Science (year 5). Finally, a dictionary in historical political science will facilitate our knowledge of the evolution of words in that particular field, from the Middle Ages to the 21st century.

600 945 €

Start date: 2008-10-01, End date: 2013-09-30

This project offers the first comprehensive study of medieval connections between the Horn of Africa and the Middle East in both Christian and Islamic contexts. It pursues the hypothesis that mobility and exchange along trade and pilgrimage routes, on both sides of and across the Red Sea, were not only vectors for the spread of Islam but also factors of African Christianities’ resiliency and reconfiguration at the same time. Medieval connections of Ethiopian and Nubian Christianities with other Eastern Christian churches have longer been studied than has been the spread of Islam across the Red Sea or along the Nile valley which remains poorly known. These parallel connections within Christen- and Islamdom across the same area have never been studied jointly, nor have been Christian-Muslim relations on such a scale. The project ultimately aims to reconnect the Horn of Africa to the global history of the area by connecting disjoint fields of research. It has the following objectives: • Providing a comprehensive survey of connections between the Horn of Africa and the Middle East (places, items, contexts) supported by a database and a geographic information system. • Analyzing human mobility in the area within three critical configurations: pilgrimages (both Christian and Muslim), slave trade and slavery, metropolization (with the case study of Cairo). • Exploring cultural transfer and dissemination in the area within and between Christen- and Islamdom through the circulation of books, models and narratives. • Evidencing regional connections and Christian-Muslim relations through archaeological survey at a very localised level: Nägaš (Ethiopia), a Muslim holy place in Christian environment related to the first exile (hijra) of Muḥammad’s companions. This project is groundbreaking in rallying around the PI historians working on the area’s various realms in their several written languages, in both Christian and Islamic contexts, from the Arab conquest until the Ottoman one.

1 859 656 €

Start date: 2017-11-01, End date: 2022-10-31

Microtubules (MTs) are dynamic cytoskeleton filaments. They permanently transit between growth and shrinkage. This famous “dynamic instability” is governed by the addition and loss of tubulin dimers at their tips. In contrast to the tip, the MT lattice was considered to be a passive structure supporting intracellular transport. However, we recently found that MT lattice is dynamic and active! Actually, tubulin dimers can be exchanged with the cytoplasmic pool along the entire length of the MT. These incorporations can repair sites on the lattice that have been mechanically damaged. These repair sites protect the MTs from depolymerisation and increase the MT’s life span. This discovery opens up a new vista for understanding MT biology. First, we will investigate the biochemical consequences of MT-lattice turnover. We hypothesise that tubulin turnover affects the recruitment of MAPs, motors and tubulin-modifying enzymes. These recruitments may feedback on lattice turnover and further regulate MT life span and functions. Second, we will investigate the mechanical impact of the MT-lattice plasticity. Tubulin removal is likely to be associated with a local reduction of MT stiffness that can impact MT shape and the propagation of forces along the lattice. We anticipate that such effects will require us to reformulate the biophysical rules directing network architecture. To achieve this, we will use reconstituted MT networks in vitro to investigate the molecular mechanism regulating MT-lattice plasticity, and cultured cells to test the physiological relevance of these mechanisms. In both approaches, microfabricated devices will be used to control the spatial boundary conditions directing MT self-organisation. By exploring the hidden 90% of MT iceberg we aim to show that the MT lattice is a dynamic mechano-sensory structure which regulates interphase MT-network architectures and possibly confers them unexpected functions.

1 998 227 €

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

My project is to write a new history of the Almohad Empire (1130-1269). This local dynasty of Berber origins ruled simultaneously over South and North of the Western Mediterranean. For the first time in history, the whole Maghreb was united under an indigenous authority. This unique historical period witnessed very important process, the political and religious separation from the East through Mahdism , and the nearly successful transfer of Islamic prophetic authority from the Arabic core to Western lands. In order to understand the exercise of power in the largest Western Muslim medieval Empire ever, I intend to use the important but largely ignored letters of the Almohad Chancery. There survive 300 documents, some of them too hastily published, which need a new scholarly edition and a usable translation. While it is well known that the Medieval Islamic world lacks in preserved archives, the review of those Letters of victory, defeat, information, advice, allegiance or reproaches will provide historians with materials that should allow a rejuvenation of the history of North African medieval land. Indeed the prevailing master narratives of the History of the medieval Maghreb is based on narrative sources. They have been systematically used as the foundation for a positivistic history. Understanding this development requires tackling the contemporary non-narrative documentary record. Yet the technical difficulties presented by the highly literary and poetic language of the chancery documents have largely barred their use by historians. This project is a methodical attempt to address this critical problem. The project will have four stages:1) taking stock of the unedited administrative documents from North Africa between the 11th and the 13thC. 2) editing of the entire corpus 3) translation of all these documents 4) presentation of a synthetic historical, linguistic and religious analysis through scholarly publications and a dedicated website

1 272 620 €

Start date: 2010-10-01, End date: 2016-09-30

Beyond Eureka seeks to challenge current understanding of how Japan became a global industrial power along with the model of how innovation takes place. Japan was the first Asian nation to industrialize and in a space of several decades went from a relatively isolated agrarian economy to an industrialized nation. The key assumption of this project is that a grasp of the salient features of the technological landscape during the pivotal period between 1800 and 1885 is an important tool for understanding Japan's industrialization. To date, this transitional period has been widely acknowledged as crucial for later development but remains empirically poorly understood. Recognizing the complexity of causation, this project seeks to use technology as a site for forging a more nuanced understanding of the emergence of Asia's first industrial power. By bringing technological change into historical focus, the project challenges the notion of innovation as necessarily a matter of disruption. In Japanese, for example, there is no conceptual or cultural equivalent to Eureka, to stand for a unique, distinct moment of individual ingenuity. If we choose the Eureka moment to epitomize the conception of innovation, early examples in Japanese industry are few and far between. Instead, a small but growing body of research shows that a sophisticated and patient examination of archives can reveal innovative processes in place of what historiography has described as borrowing, imitation or adaptation. This project seeks to foreground innovation as a long-term process of accumulation in which the new only could only work by taking root and embedding itself within the old, not by replacing it and starting from scratch. The team, comprising the PI and five postdoctoral fellows, will combine expertise and previously unexamined archives to bring depth and nuance to not only to the specific case of Japanese industrialization, but also more broadly of innovative processes in human past.

1 373 500 €

Start date: 2020-02-01, End date: 2025-01-31

The central purpose of this project is to bring down interdisciplinary barriers by showing how the Slavic and the Jewish heritage can each be approached as a unique repository of the unknown texts, traditions, and sensibilities of the other. By focusing on previously unexplored or under-explored medieval texts, I aim to reconstruct the Jewish and Slavic legacies, some of whose materials have been considered lost, while others were misinterpreted or neglected. This research project will resort to historical and philological techniques hitherto considered mutually incompatible in this field. The study intends to use methods of cultural archaeology to explore medieval Judeo-Slavic transparency. By cultural transparency we understand the mutual permeability of different cultures, which facilitates the exchange of ideas and genres of creativity between them. Cultural archeology involves methods of multi-disciplinary research based on the assumption that Eastern Europe constituted a melting pot characterized by an intensive cross-fertilization of cultural legacies. Cultural archaeology studies different historical, religious, and literary texts by looking at them as a palimpsest in which earlier texts and types of discourse come to the fore as shaped by their contemporary socio-cultural settings. The proposed theme has far-reaching methodological implications beyond the Judeo-Slavic cultural realm. This project will build a model of cross-cultural interaction to achieve a better understanding of the situations in which different faith-based ethnic cultures cohabit.

1 044 000 €

Start date: 2010-11-01, End date: 2016-10-31

“JudgingHistories” sets out to examine the epistemic premises innate to universalizing historical experience, by scrutinizing the quest for historical understanding and moral judgment against the backdrop of an emerging global cultural environment, fraught with multiple recollections, while using memories of World War II as the empirical core of the study. The pivotal constellation of research emerges by interfacing a horizontal (West-East) alignment traditionally significant for continental European history with a vertically oriented alignment (North-South) that sheds a colonial and post-colonial perspective on World War II. This constellation tends to lead a posteriori to a realm of conflicting, morally permeated discourses of comparison and analogy, revealing the Holocaust to function as the central event of continental narration, on the one hand, while genocidal atrocities highlight the colonial or post-colonial comprehension, perception and narration, on the other. Methodologically, and in order to offer a fresh and innovative view of the emergence of the specifics of knowledge and meaning in the domain of historical understanding in a globalizing world, while placing the signifying event of the Nazis’ systematic annihilation of the Jews at the heart of the question of universal historical judgment, the project proceeds from the colonial periphery of events, however. This “peripheral”, colonial perspective will in a further seemingly paradoxical turn find itself extended into continental European affairs where it functions to help us comprehend the multiplicity of experiences and the diversity of attendant memories unfolding there. Such a research perspective may epistemologically enable us to reconstruct a universally convincing and valid understanding of a foundational event in European and global history, namely the recollection of World War II, and thus render possible common judgment while re-determining the meaning of “History”.

2 499 260 €

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

The overarching goal of L2STAT is to understand L2 literacy acquisition by bringing together, for the first time, recent advances in the neurobiology of statistical learning (SL), a detailed statistical characterization of the world’s writing systems, and neurally-plausible general principles of learning, representation, and processing. L2STAT aims to provide a new theoretical framework that considers L2 learning and SL a two-way street: SL, on the one hand, tunes learners to the regularities of a new linguistic environment, and on the other hand, L2 environment shapes learners’ sensitivity to its specific types of statistical properties. The project will focus on the assimilation of reading skills in four novel linguistic environments, and investigate how exposure to their distinct writing systems shape, in turn, SL. L2STAT is an interdisciplinary project that launches in parallel five mutually informative research axes: 1) we employ advanced methods from computational linguistics and machine learning to precisely characterize the statistics of four highly contrasting writing systems (English, Spanish, Hebrew, Chinese). 2) We study the learning that results from biologically-inspired computational models that are exposed to these statistics, to generate a priori predictions regarding what statistical properties can (or cannot) be learned, and how neural mechanisms constrain the representations learned during L2 literacy acquisition. 3) We develop psychometrically reliable behavioral tests of individuals’ capacities to extract regularities in the visual and auditory modalities. 4) We use state of the art neuroimaging techniques including EEG, MEG, fMRI to probe the neurobiological underpinning for detecting regularities in the visual and auditory modalities. 5) We conduct behavioral experimentation in four sites (Israel, Spain, Taiwan to track literacy acquisition longitudinally in the four different languages.

2 500 000 €

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

The Liber Glossarum is a very large dictionary (about 30000 entries), compiled in Northern France at the end of the VIIIth c., and combining encyclopaedic, theological, medical and grammatical sources. While being the first European alphabetical dictionary, it is still much neglected by modern scholars, principally because there exist only partial editions from the beginning of the XXth c. This project aims to provide a full edition of the text, based upon a large number of manuscripts, as well as to try and answer questions relative to its origin (which female monastery ?), its sources (which library was used ?), its link with the Carolingian educational reform movement inspired the Carolingian court. The edition will be completed within a few years, by a team composed of palaeographers, mediaevalists, and specialists of the various sources from which the authors of the Liber borrowed. The core of the project will be the Website http://liber-glossarum.linguist.univ-paris-diderot.fr/, used as a platform allowing European partners to work easily in common. Such a complete edition of the Liber glossarum intends to be a solid foundation for future scholarship, allowing also closer examination of the Carolingian manuscript tradition of the great encyclopaedist Isidore of Seville, as well as a better evaluation of the importance of the Liber for the whole lexicographical tradition of the Middle Ages. Its study is of interest from three perspectives : it will provide better knowledge of a tool that was diffused throughout Europe; it will enhance our understanding of the role of well-read women in building the foundations of medieval culture ; and from a linguistic point of view, it will give an overview of the principles at work in the making of European dictionaries.

945 571 €

Start date: 2011-02-01, End date: 2016-07-31

Adult speakers of a language know several tens of thousands of words. Unless they suffer from some neurological disorders, those words can be readily used on a daily basis. This is done by retrieving lexical information from long term memory, and selecting its most relevant aspects. Cognitive models of word selection distinguish stages of processing concerned with semantic, lexical, and form properties of the words. Contrastive hypothesis have been considered to describe how appropriate lexical items are uniquely identified among all known words. Various sections of temporal cortex are known to play a prominent role in lexico-semantic processing, whereas frontal cortex is known to act as a controller of memory retrieval. More specifically, posterior left lateral and medial areas are capable to detect and resolve conflict among candidate words in cases where uncertainty arises. Despite detailed accounts, current descriptions of lexical information processes are rather static. Discussions of cognitive processing models have often been framed on structural, rather than dynamical, arguments. In addition, a vast majority of studies characterizing lexical information processing are based on low temporal resolution brain imaging techniques. The main objective of this project is to go beyond these descriptions by characterizing the spatio-temporal dynamics of word selection processes. The evidence will come from electro-encephalographic (EEG) and magneto-encephalographic (MEG) recordings of brain activity elicited in well-defined cognitive tasks. Innovative temporal pre-processes should allow discriminating brain activity from articulation artefacts. The evidence will also come from intra-cranial event related potentials, recorded in patients suffering from pharmaco-resistant forms of frontal and temporal lobe epilepsy. These data have high spatial and temporal resolution, and will provide strong constrains on lexical information processing models. A description of the dynamic interactions between brain regions during word selection will change the way we think about this basic behaviour. Besides this intrinsic interest, word selection provides a very natural way to connect relatively simple decision processes (e.g. those engaged in basic visuo-motor tasks) with more integrative processes involved in information retrieval from long term memory. Better understanding the spatio-temporal dynamics of lexical information processes will also be highly valuable for improving pre-surgical evaluation procedures in pharmaco-resistant epilepsy.

1 251 345 €

Start date: 2011-04-01, End date: 2016-03-31

Plant development is continuous throughout their lifetime and reflects their ability to adapt to their environment. This developmental plasticity is very obvious in the development of the root system. Surprisingly, the fundamental mechanisms of root development have been studied into great detail but the effect of the environment on its plasticity is still largely unknown. I will use phosphate, since this nutrient has a very low mobility in soil, as a mean to study plant developmental adaptation in white lupin. This species has developed extreme adaptive mechanism to improve phosphate uptake by producing structures called “cluster roots”. They are dense clusters of lateral roots with determinate development and highly specific physiology. I will develop new tools to identify cluster root mutants in white lupin, sequence white lupin genome, perform tissues specific transcriptomics and perform full molecular characterization of selected genes. This project will also lead me to compare adaptive mechanisms between white lupin and narrow-leafed lupin, a closely related species that does not produce cluster roots. We will also test whether it is possible to transfer the ability to form cluster roots in this species. Altogether, this project will lead to a major advance in our capacity to understand how plants are able to sense and respond to their environment and how evolution has selected adaptive developmental mechanisms to improve their capacity to use limited resources. This project focuses on the most extreme developmental adaptation produced in response to phosphate starvation. It is ambitious, as it will necessitate the development of several tools. However, it is highly feasible since it builds on my previous experience and important outcome can be expected in term of crop improvement and means to reduce the use of phosphate fertilizers.

1 997 103 €

Start date: 2015-09-01, End date: 2020-08-31

One of the most striking demonstrations of experience-dependent plasticity comes from studies of blind individuals showing that the occipital cortex (traditionally considered as purely visual) massively changes its functional tuning to support the processing of non-visual inputs. These mechanisms of crossmodal plasticity, classically considered compensatory, inevitably raise crucial challenges for sight-restoration. The neglected relation between crossmodal plasticity and sight-recovery will represent the testing ground of MADVIS in order to gain important novel insights on how specific brain regions become, stay and change their functional tuning toward the processing of specific stimuli. The main goal of MADVIS is therefore to make a breakthrough on two fronts: (1) understanding how visual deprivation at different sensitive periods in development affects the functional organization and connectivity of the occipital cortex; and (2) use the fundamental knowledge derived from (1) to test and predict the outcome of sight restoration. Using a pioneering interdisciplinary approach that crosses the boundaries between cognitive neurosciences and ophthalmology, MADVIS will have a large impact on our understanding of how experience at different sensitive periods shapes the response properties of specific brain regions. Finally, in its attempt to fill the existing gap between crossmodal reorganization and sight restoration, MADVIS will eventually pave the way for a new generation of predictive surveys prior to sensory restoration.

1 488 987 €

Start date: 2014-04-01, End date: 2019-03-31

Humans and other animals possess dedicated systems of core knowledge to represent numeric and geometric information. In the case of number at least, these representations are abstract (independent of the format of the stimuli represented), they are present early in life, and they can be used to compute the outcome of simple arithmetic problems. Such intuitive knowledge is thought to guide the acquisition of elaborate concepts of numbers and geometry. However, core systems of representations for numbers and geometry fall short of providing the representational power to support even the most fundamental mathematical concepts: Integers, and Euclidean geometry. In this research project, we are seeking to understand the process of knowledge construction by which children acquire adult-like numeric and geometric concepts, focusing on two case studies: exact numbers, and plane angles. Our approach is multidisciplinary, bringing together researchers from the fields of developmental psychology, cognitive neuroimaging, and linguistics. For both number and geometry, we will first start by characterizing core intuitions in behavioural studies involving infants and children. Second, we will look at the factors influencing the acquisition of more elaborate concepts based these core intuitions. In order to separate the factors of age, education, and environment, we will conduct studies with occidental children, as well as children and adults from the Amazon. Third, we ultimately aim at studying the neural bases of conceptual changes in childhood, and in this perspective we are planning brain imagining experiments in adults. Once we have a thorough description of the neural codes for number and geometry in adults, we will be in position to ask which aspects of the code have undergone change during childhood, as new knowledge was being constructed.

1 394 130 €

Start date: 2011-04-01, End date: 2016-08-31