ERC FUNDED PROJECTS

Alfonsine astronomy is arguably among the first European scientific achievements. It shaped a scene for actors like Regiomontanus or Copernicus. There is however little detailed historical analysis encompassing its development in its full breadth. ALFA addresses this issue by studying tables, instruments, mathematical and theoretical texts in a methodologically innovative way relying on approaches from the history of manuscript cultures, history of mathematics, and history of astronomy. ALFA integrates these approaches not only to benefit from different perspectives but also to build new questions from their interactions. For instance the analysis of mathematical practices in astral sciences manuscripts induces new ways to analyse the documents and to think about astronomical questions. Relying on these approaches the main objectives of ALFA are thus to: - Retrace the development of the corpus of Alfonsine texts from its origin in the second half of the 13th century to the end of the 15th century by following, on the manuscript level, the milieus fostering it; - Analyse the Alfonsine astronomers’ practices, their relations to mathematics, to the natural world, to proofs and justification, their intellectual context and audiences; - Build a meaningful narrative showing how astronomers in different milieus with diverse practices shaped, also from Arabic materials, an original scientific scene in Europe. ALFA will shed new light on the intellectual history of the late medieval period as a whole and produce a better understanding of its relations to related scientific periods in Europe and beyond. It will also produce methodological breakthroughs impacting the ways history of knowledge is practiced outside the field of ancient and medieval sciences. Efforts will be devoted to bring these results not only to the relevant scholarly communities but also to a wider audience as a resource in the public debates around science, knowledge and culture.

1 871 250 €

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

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

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

1 997 675 €

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

Shape-persistent organic cage compounds consisting only of covalent bonds are fascinating synthetically targets, because they are studied as hosts for the selective recognition of guest molecules, such as artificial lectins, for catalysis in confined space or for the construction of a new type of porous material. For the latter, the shape-persistency and rigidity of the cage cavity is of utmost importance. There are in principle two existing strategies for the synthesis of shape-persistent organic cage compounds. Strategy I: A stepwise approach by irreversible reactions. Here, the advantage is the chemical stability of the target compound due to the intrinsic stabilities of the formed bonds. The disadvantage of this approach is in general the low overall yield, because the system does not allow any ‘self-correction’ of once formed bonds. This is different for the other approach used in Strategy II: By using dynamic covalent bond formation as synthetic tool, shape-persistent organic cages can be constructed from rather simple molecular building blocks in one step. Here, the yields are usually very high or even quantitatively, because the reversibility of the reaction allows the system to self-correct. Unfortunately, the resulting compounds are more prone to chemical cleavage of the cages than those synthesized by the irreversible approach. Within this project, we will combine the advantages of both strategies to synthesize chemically and thermally stable nano-sized discrete organic cage compounds in a two-step approach in high yields. To demonstrate the versatility and synthetic power of this approach, pure hydrocarbon cages will be synthesized in a few steps in high yields. Finally, this strategy will make for the first time open and closed-shell fullerenes and heterofullerenes that are isomerically pure, accessible.

1 996 000 €

Start date: 2017-04-01, End date: 2022-03-31

Understanding how neural circuits process and encode information is a fundamental goal in neuroscience. For the neural network of the retina, such knowledge is also of concrete importance for the development of vision restoration therapies for patients suffering from degeneration of photoreceptors. Artificial stimulation of retinal neurons through electronic implants or inserted light-sensitive proteins (“optogenetics”) aims at reconstructing natural transmission of visual information to the brain. Recreating natural retinal activity, however, will require a thorough understanding of the complex and diverse neural code of the retina. The challenge lies in deciphering the various nonlinear operations and dynamics in the around 30 parallel signalling streams that emerge from the retina, represented by as many types of ganglion cells, the retina’s output neurons. The CODE4Vision project will tackle this challenge by identifying the effective connectivity between the different types of retinal ganglion cells and their excitatory presynaptic partners, bipolar cells, and by determining the features of information processing between these neuronal layers. We will characterize the layout of bipolar cell inputs to large populations of ganglion cells with novel analyses that we derive from computational statistics and machine learning. We will then study the nonlinear and dynamical features of these connections by designing closed-loop experiments that automatically adjust visual stimuli to the identified layout of bipolar cells. These analyses will be supplemented by direct measurements of connections through simultaneous bipolar and ganglion cell recordings. The results will pave the way towards new models of how the retina encodes natural visual stimuli. Finally, we will apply this knowledge to mouse models of optogenetic vision restoration in order to develop stimulation schemes that emulate natural retinal stimulus encoding.

1 991 445 €

Start date: 2017-06-01, End date: 2022-05-31

The most important open questions in European paleoanthropology concern the timing, number and origin of early human dispersals into the continent, the identity and number of taxa present, and their possible interactions. These issues remain unresolved partly due to the lack of research in South-East Europe, a region at the crossroads between continents and a refugium for fauna, flora and possibly human populations during glacial times. The PI’s previous work there (ERC StG PaGE) aimed to add new evidence to further our understanding of human evolution on the continent. PaGE led to the discovery of several new Paleolithic sites, including the oldest radiometrically dated archaeological site from South-East Europe, placing the region squarely in the Paleolithic map of Europe. CROSSROADS is an ambitious, groundbreaking research program that builds on the foundation of PaGE to take Paleolithic research in the region to a new level. In contrast to the exploratory goals of PaGE, it focuses on the early part of the Paleolithic targeting the following questions: Can human presence in South-East Europe, considered a major dispersal route into the continent from Africa and the Near East, be documented beyond the current known chronology of ca. 500 ka BP, as shown in the West? Is there a gap between the earliest human arrival and subsequent human activity in the region, or was human habitation continuous, as would be expected in a refugium? What was the environmental backdrop of the early human dispersal and subsequent evolution? How did behavioral / biological change correlate with environmental changes, chronology and landscape use? Can we document a higher level of diversity in the human fossil record of the region than would be expected under evolutionary scenarios developed on Western European evidence, suggesting that different evolutionary processes were at work? The answers to these questions will be essential for testing hypotheses about human evolution in Eurasia.

1 999 250 €

Start date: 2017-04-01, End date: 2022-03-31

Graphene nanoribbons (NR) are quasi-1D nanostructures with discrete band gaps, ballistic conduction, and one-atom thickness. Such properties make them ideal candidates to develop low-dimensional semiconductors, which are essential components in nanoelectronics. Atomically-precise control over the structure of NR (width, length, edge, doping) is crucial to fully exploit their potential. However, current approaches for the synthesis of NR suffer from several drawbacks that do not allow attaining such level of precision, therefore alternative methods need to be sought. e-Sequence will develop an unprecedented approach that assembles stepwise small molecular building blocks into NR to specifically target the most important challenges in NR synthesis. Such approach will enable the preparation of an unlimited number of NR with atomically-precise control over their structure and with almost no synthetic and purification effort, exceeding the limits of existing methods. The impact of e-Sequence will not be limited to NR synthesis but it will also extend to other disciplines, since NR are promising candidates to develop new technologies with applications in electronics, sensing, photonics, energy storage and conversion, spintronics, etc. e-Sequence ambitious research programme will be orchestrated by an independent scientist with an excellent track record of achievements in low-dimensional carbon nanostructures, and who has already established a fledgling and internationally competitive research group. Building on this and on his recent permanent appointment as Research Professor, the award of this ERC project will enable him to consolidate his group, build a portfolio of excellent research, and produce results that compete on the world stage.

2 000 000 €

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

The astonishing properties of the f-elements have been exploited in numerous consumer technologies, despite their fundamental chemistry being poorly developed. It is now crucial to address this issue to provide the necessary insights to develop future applications. Design criteria exist to build f-element complexes with maximised physical attributes. This adventurous proposal targets the synthesis and thorough analysis of two complementary molecular f-element architectures that 1) optimise magnetic properties and 2) stabilise unusual oxidation states. In Part 1, we target highly axial f-element complexes that lack equatorial ligand interactions. These molecules can exhibit maximised single-molecule magnet properties, including magnetic hysteresis, a memory effect and as a prerequisite of data storage, at liquid nitrogen temperatures. This is the necessary first step towards achieving high-density molecular data storage without expensive liquid helium cooling and future commercial applications. In Part 2, we target trigonal f-element complexes that lack axial ligand interactions. These are optimal ligand fields for the stabilisation of low oxidation states, thus we aim for rare lanthanide/actinide(II) and unprecedented lanthanide/actinide(I) complexes. These compounds are ideal candidates for unique measurements of covalency by pulsed electron paramagnetic resonance spectroscopy, which will provide textbook data that can be transferable to nuclear fuel cycles. An ERC CoG will provide the necessary resources to build a world-leading research team that will deliver landmark synthetic results and fresh insights into f-element electronic structure, whilst opening up new chemical space for future exploitation. These findings will underpin current technologies and will facilitate the discovery of future applications, supporting key Horizon 2020 priority areas including the Flagship on Quantum Technologies, and enhancing the scientific reputation and economy of the EU.

1 990 801 €

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

The major objective of FUNCOPLAN is to examine groundbreaking questions on the functional role of newly-generated neurons in the adult brain. Using a combination of innovative approaches, our aim is to discover how plasticity in adult-born cells shapes information processing in neuronal circuits. Adult neurogenesis produces new neurons in particular areas of the mammalian brain throughout life. Because they undergo a transient period of heightened plasticity, these freshly-generated cells are believed to bring unique properties to the circuits they join – a continual influx of new, immature cells is believed to provide a level of plasticity not achievable by the mature, resident network alone. But what exactly is the function of the additional plasticity provided by adult-born neurons? How does it influence information processing in neuronal networks? These questions are vital for our fundamental understanding of how the brain works. We will address them by studying a unique population of cells that is continually generated throughout life: dopaminergic neurons in the olfactory bulb. These cells play a key role in the modulation of early sensory responses and are renowned for their plastic capacity. However, the role of this plasticity in shaping sensory processing remains completely unknown. FUNCOPLAN’s first objectives, therefore, are to discover novel experience-dependent plastic changes in the cellular features and sensory response properties of adult-born neurons. We will then go much further than this, however, by integrating our discoveries with state-of-the-art techniques for precisely manipulating activity in these cells in vivo. This wholly innovative approach will allow us to mimic the effects of plasticity in naïve circuits, or cancel the effects of plasticity in experience-altered networks. In this way, we will break new ground, demonstrating a unique contribution of plasticity in adult-born cells to the fundamental function of neuronal circuitry.

2 000 000 €

Start date: 2017-06-01, End date: 2022-05-31

Medieval public health is mired in modern myth: without centralized governments, democratic values and advanced medicine, promoting health at the population level was purportedly either unthinkable or simply impractical. Offering a radically different view, HealthScaping will document, analyze and disseminate knowledge about preventative public healthcare between 1200-1500, an era of accelerated urbanization followed by massive demographic decline, with the onset of Black Death (1347-51). This long-term and comparative perspective will fundamentally revise the narrative of European public health by tracing the development and impact of pertinent government policies, medical discourses and social and religious action in the continent’s two most urbanized and richly documented regions, Italy and the Low Countries. The project taps numerous written, material and visual sources and archaeological data from several sites, and examines them also by critically engaging the insights of governmentality studies, cultural-spatial analysis and actor-network theory. A multidisciplinary team, working in a Geographical Information Systems environment and generating innovative urban health maps, will recover earlier societies’ struggles with domestic and industrial waste, travel and labor hazards, food quality, and social and religious behaviors considered harmful or dangerous. As such, the project’s implications will be broad and profound, for it will 1) dislodge bio-power from its accustomed place in modernity; 2) historicize the concept of the public sphere from a health perspective; and 3) challenge the privileged role given to epidemic disease as a catalyst for environmental interventions in premodernity. It will also 4) generate new insights for public health scholars and practitioners working today around the globe, by rethinking the feasibility of preventative interventions under highly diverse forms of government, culture and topography.

1 998 004 €

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

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

InOutBioLight aims to design multifunctional rubbers with enhanced mechanical, thermal, color-converting, and light-guiding features towards advanced biohybrid lighting and photovoltaic technologies. The latter are placed at the forefront of the EU efforts for low-cost production and efficient consumption of electricity, a critical issue for a sustainable development. In this context, the use of biomolecules as functional components in lighting and photovoltaic devices is still a challenge, as they quickly denature under storage and device operation conditions. This paradigm has changed using an innovative rubber-like material, in which the biofunctionality is long preserved. As a proof-of-concept, color down-converting rubbers based on fluorescent proteins were used to design the first biohybrid white light-emitting diode (bio-HWLED). To develop a new generation of biohybrid devices, InOutBioLight will address the following critical issues, namely i) the nature of the protein-matrix stabilization, ii) how to enhance the thermal/mechanical features, iii) how to design multifunctional rubbers, iv) how to mimic natural patterns for light-guiding, and v) how to expand the technological use of the rubber approach. To achieve these goals, InOutBioLight involves comprehensive spectroscopic, microscopic, and mechanical studies to investigate the protein-matrix interaction using new polymer matrices, additives, and protein-based nanoparticles. In addition, the mechanical, thermal, and light-coupling features will be enhanced using structural biocompounds and reproducing biomorphic patterns. As such, InOutBioLight offers three major advances: i) a thorough scientific basis for the rubber approach, ii) a significant thrust of the emerging bio-HWLEDs, and iii) innovative breakthroughs beyond state-of-the-art biohybrid solar cells.

1 999 188 €

Start date: 2020-01-01, End date: 2024-12-31

Research in 2D materials has increased dramatically since the first isolation of graphene in 2004, with diverse interdisciplinary studies. In the last few years, 2D material research expanded beyond graphene by the development of other 2D materials, such as monolayered transition metal dichalcogenides, black phosphorous, and Boron Nitride. There are hundreds of possible 2D crystals that can be isolated, with properties ranging from metallic, semi-metallic, semiconducting to insulating, depending on the material composition. Semiconducting 2D materials have attracting interest in next-generation electronics/opto-electronics such as transistors, photo-gated transistors, photo-detectors, solar cells, and light emitting devices (LEDs), molecular sensors and optical imaging sensors. The unique structural form of 2D materials provides several benefits over other existing materials: ultrathin, flexible, highly transparent, large surface to volume ratio, and 2D quantum confinement. High transparency LEDs are required for applications in transparent displays on glass panels. Many 2D based opto-electronic devices have used mechanical exfoliation from bulk crystals, but this is limited to small areas. Recent work on chemical vapour deposition (CVD) to grow wafer-scale 2D materials has opened up exciting opportunities for commercial exploitation and has accelerated the intensity of research in this field towards real applications. The vision of this proposal is to realize a new class of ultra-thin, flexible, large-area, transparent, high-sensitivity opto-electronic device arrays based on all 2D materials, with a focus on imaging sensors and LEDs. This will involve wafer-scale CVD synthesis of 2D materials including novel blue and green 2D semiconductors, optical spectroscopy to probe the interlayer interactions, atomic level structure-property correlations using advanced electron microscopy, and the nanoscale fabrication and testing of high efficiency devices.

1 999 318 €

Start date: 2017-04-01, End date: 2022-03-31

Major advances were made in understanding circuits that underlie aversive emotional learning. The majority gained by using classical associative models, mainly tone/context-shock conditioning. Failure to extinguish the response or to discriminate from other safe stimuli (generalization), form two main animal models for human anxiety-disorders and post-traumatic-stress. These simple yet powerful approaches enabled cutting-edge techniques in rodents to unveil amygdala circuitry and its connectivity with the medial-prefrontal-cortex. Yet, we have less understanding of the mechanisms that underlie elaborated behavioural models of mal-adaptive behaviour, as well as less understanding of neural codes and computations in the evolutionary-expanded primate amygdala. Our lab recently embarked on exploring these venues by pioneering physiological studies of generalization and extinction protocols in primates. The goal of the current project is to develop behavioural models of complex learning and maladaptive behaviour, and then examine and shed light on the underlying computations in primate amygdala-PFC circuit. We design a novel rule-based learning task, and examine its acquisition, extinction, generalization and exploration-exploitation trade-off in dangerous environments. Specifically, the concepts of rule learning and exploration-exploitation tradeoff form novel insights and aspects of [mal-]adaptive behaviours, and will suggest new animal models of learned anxiety. We record dozens of neurons in the amygdala and prefrontal-cortex simultaneously using deep multi-contact arrays, supplemented by stimulation to address functional connectivity, and development of modelling approaches for the behaviour and neural codes. We posit that the development of more [complex] models is crucial and the next logical step in achieving translation of animal models of anxiety disorders, as well as in understanding basic mechanisms behind the rich repertoire of emotional behaviours.

2 000 000 €

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

"Living organisms are sophisticated self-assembled structures that exist and operate far from thermodynamic equilibrium and, as such, represent the ultimate example of dissipative self-assembly. They remain stable at highly organized (low-entropy) states owing to the continuous consumption of energy stored in ""chemical fuels"", which they convert into low-energy waste. Dissipative self-assembly is ubiquitous in nature, where it gives rise to complex structures and properties such as self-healing, homeostasis, and camouflage. In sharp contrast, nearly all man-made materials are static: they are designed to serve a given purpose rather than to exhibit different properties dependent on external conditions. Developing the means to rationally design dissipative self-assembly constructs will greatly impact a range of industries, including the pharmaceutical and energy sectors. The goal of the proposed research program is to develop novel principles for designing dissipative self-assembly systems and to fabricate a range of dissipative materials based on these principles. To achieve this goal, we will employ novel, unconventional approaches based predominantly on integrating organic and colloidal-inorganic building blocks. Specifically, we will (WP1) drive dissipative self-assembly using chemical reactions such as polymerization, oxidation of sugars, and CO2-to-methanol conversion, (WP2) develop new modes of intrinsically dissipative self-assembly, whereby the activated building blocks are inherently unstable, and (WP3&4) conceive systems whereby self-assembly is spontaneously followed by disassembly. The proposed studies will lead to new classes of ""driven"" materials with features such as tunable lifetimes, time-dependent electrical conductivity, and dynamic exchange of building blocks. Overall, this project will lay the foundations for developing new synthetic dissipative materials, bringing us closer to the rich and varied functionality of materials found in nature."

1 999 572 €

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

Migrations are a central issue of the modern period, particularly since World War One. At the same time, the implementation of a systematic policy of categorization, discrimination, persecution, and extermination of European Jews is one of the major events of the first half of the 20th century. How should the relations between these two histories be understood? The goal of this project is to explore the links between migration and the Holocaust from a transnational microhistorical perspective. To this end, it will implement an original method: producing the collective biography of the Jewish inhabitants from the Polish shtetl of Lubartow from the 1920s to the 1950s, whether they emigrated or stayed behind, whether they were exterminated or survived the Holocaust. This research will, for the first time, reconstruct the trajectories of a group of persecution victims across the different places they travelled through, which is possible today thanks to new access to an impressive body of archives and the affordances of the digital humanities. The methodological and archival challenge is immense. This transnational collective biography explores the directions of individual journeys, the diversity of fates, as well as the connections between those who remained and those who left. By doing so, the LUBARTWORLD project addresses some prominent theoretical issues: the dynamics of a social structure drawn into a major disruption, the variability of social categorizations in diverse national and political contexts, and the complex making of identities. From an epistemological point of view, it will develop innovative ways of reconstructing and analyzing life-course information. Although the project begins with Lubartow, it leads to the world in its globality. Lubartow residents crisscrossed the globe, and their trajectories outline and embody in their own way the upheavals of Europe’s relations with the world before, during, and after the Holocaust.

1 985 083 €

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

Neuronal lamination is a hallmark of many diverse brain areas where it is important for efficient circuit formation and neuronal wiring. Despite this significance, the cellular and tissue scale principles that ensure successful and robust lamination are not fully understood. In particular, how cell-tissue interactions and biomechanics influence neuronal lamination is only scarcely explored. To fill this gap, we will use the vertebrate retina with its five neuronal cell types arranged in a highly ordered pattern to investigate the emergence of neuronal lamination. We will initially use the zebrafish system and employ long term light sheet imaging to reveal the migration behaviour of the different retinal neurons. Based on this, transcriptomics approaches will enable the dissection of cellular pathways and extracellular cues involved in neuronal migration and overall lamination. To dissect how biomechanics influence lamination, we will use Brillouin microscopy to explore the influence of changing tissue stiffness on lamination and test the role of differential adhesion. These combined results will be the basis to expand studies to the human system and ex vivo human organoids to generate insights into human retinal development. To date, systematic studies investigating molecular pathways in combination with biophysical parameters to understand brain formation across model systems are rare. Due to our previous expertise, we are in an excellent position to perform such interdisciplinary, integrative and interspecies approach. This will unveil common denominators of retinal neuronal lamination in zebrafish, humans and human organoids and thereby reveal the similarities of retinal development in different species and how developmental programs compare in vivo versus ex vivo. In addition, while this proposal focuses on neural lamination in the retina, findings will also inspire future cross-disciplinary studies investigating neuronal lamination in other parts of the brain.

1 923 750 €

Start date: 2019-10-01, End date: 2024-09-30

Artificial molecular motors and switches have the potential to become a core part of nanotechnology. However, a wide gap in length scales still remains unaccounted for, between the operation of these molecules in solution, where their individual mechanical action is randomly dispersed in the Brownian storm, and on the other hand their action at the macroscopic level, e.g. in polymer networks and crystals. This proposal is about bridging this gap, by developing chemo-mechanical transduction strategies that will allow dynamic molecules to perform a range of unprecedented tasks, e.g. by generating strong directional forces at the nanoscale, and through shape-shifting microscopic formations. This project aims to harness the mechanically-purposeful motion of dynamic molecules as to generate measurable forces from the nanoscale, and ultimately establish operational principles for chemo-mechanical transduction in supramolecular systems. In my wholly synthetic approach, I draw inspiration from the operational principles of microtubules. I will incorporate molecular photo-switches into supramolecular tubes, and enable the controlled growth and disassembly of the tubes by using light as the energy input. Thus, I will: (i) Synthesize stiff supramolecular tubes that grow actively under continuous illumination, and disassemble with a power stroke as soon as illumination stops; (ii) Measure, and harvest the forces generated by the tubes to manipulate individual nanoparticles with a sense of directionality; and (iii) Encapsulate the tubes into water droplets and vesicles, to yield shape-shifting, and eventually rudimentary splitting models for cells. This project reaches beyond the state of the art in adaptive molecular nano-systems, by pioneering strategies to engineer and harness strain in supramolecular assemblies. It thus lays the foundations for machineries that are capable of manipulating matter at length scales that are also those at which the cytoskeleton operates.

2 000 000 €

Start date: 2019-03-01, End date: 2024-02-29

The aim of this project is to study the influence of sleep in the establishment of aversive memory and to propose a proof of concept for the use of brain-computer interfaces during sleep to treat pathologies associated with fear or anxiety such as post-traumatic stress disorders. It is now accepted that sleep plays a crucial role in memory consolidation processes that allow the conversion of newly encoded memory traces into more stable information. Numerous studies have shown that some of the positive effect of sleep on consolidation relies on the reactivations of previous experiences. We recently showed that spontaneous sleep reactivations can be used to create an artificial memory during sleep. We made electrical stimulations of a brain reward center contingent on the spontaneous reactivations of a hippocampal place cell during sleep. After this procedure, mice developed a place preference for the location of the place field of the trigger cell, showing that a place/reward association had been created. Our experiment, as most of the studies on place cells or reactivations, was done with appetitive learning and we now intend to tackle this issue in the context of aversive learning. In this project, we will use our closed-loop device to address long lasting controversies such as the existence of reactivations in deep SWS or REM sleep. We will also investigate how avoided places are represented in the hippocampus and whether they are more reactivated during subsequent sleep. Additionally, we will show whether aversive-related wake preplays can be actively modulated, suggesting that “intrusive memories” or rumination can be addressed in animal models. Finally, we will test whether an aversive association performed during wake can be modified by our closed-loop-driven appetitive association during sleep. This would bring the proof of concept that sleep could be used to erase aversive memories in pathological situations such as post-traumatic stress disorders.

1 998 250 €

Start date: 2017-10-01, End date: 2022-09-30

The goal of the MULTIPROSMM project is to design systems able to present magnetic bistabilities under different stimuli (temperature, magnetic field or light) on an unprecedented large temperature range, i.e. very low temperature with Single Molecule Magnet (SMM) behaviour, intermediate temperature with Light Induced Excited State Trapping (LIESST) and high temperature with SpinCrossOver (SCO). On one hand, as a photography of the energy-splitting of the spectroscopic states, the lanthanide luminescence will be used as a key tool for the understanding of the magnetic properties of lanthanide ions. On the other hand, Circularly Polarized Luminescence (CPL) combines the sensitivity of the luminescence with crucial information on the chiral environment. A step by step synthetic strategy will be used to elaborate molecular systems in which the coexistence of i) SMM and SCO; ii) SMM and CPL and iii) SMM, SCO and CPL are operating. The enhancement of the magnetic properties is needed to step forward towards applications. To reach such optimizations, the quantum regime of the SMM and the internal magnetic field must be vanished playing with the hyperfine coupling and magnetic dilutions. Both isotopic enrichment and shaping (i.e. decoration of both mesoporous silica and nanoparticle surfaces) of the designed systems could allow high magnetic performance in multiple properties SMM. The final result could be a system suitable for very high density data storage on a wide temperature range (from cryogenic to room temperature).

1 505 000 €

Start date: 2017-08-01, End date: 2022-07-31

For almost 100 years, the evolution of humans has been summarized as a transition from small-brained bipeds with an ape-like body plan (referred to as australopiths), to large-brained striding bipeds with a human-like body plan (members of the genus Homo). This characterisation dominates popular perception of human evolution in the public sphere. However, three newly discovered fossil human (hominin) species (H. naledi, H. floresiensis and Australopithecus sediba) do not fit this simple transitional model in either morphology or time (the former two surviving contemporaneously with modern humans), and have re-ignited debate about the origin of the Homo lineage, including perceptions of the earliest putative Homo species, H. habilis. These new fossils raise fundamental questions about the ecological niches occupied by hominins and the inferred transitions between niches throughout human evolution. With NewHuman, I will pioneer a novel, interdisciplinary and holistic approach using cutting-edge analyses of internal structures of fossil hominin teeth and bones to reconstruct the adaptive niche of these enigmatic species and test whether there is an unrecognized adaptive branch on the human family tree. Specifically, NewHuman will employ ground-breaking imaging techniques and analytical tools to reveal never-before-examined tooth and bone structures in these hominins. In doing so, it will 1) characterize the behaviour of these enigmatic species and place them more firmly into their ecological environment; and 2) elucidate the adaptive strategy that was likely the transition from australopith-like hominin species to later Homo, but which also represents a highly successful lifeway that persisted for over 2 million years alongside the evolving human lineage. By achieving these ambitious aims, NewHuman will have a significant impact on hypotheses about human evolution, and could result in a paradigm shift that overturns current views on human evolutionary history.

1 998 644 €

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

While the functions of sleep are still a matter of debate and may include memory consolidation, brain clearance, anabolism and plasticity, the neural substrates of sleep and wake states are the subject of intense study. Successive sleep-wake cycles rely on an appropriate balance between sleep-promoting nuclei of the brain located in the anterior hypothalamus and, arousal-promoting nuclei from the posterior hypothalamus and the brainstem. My laboratory identified different subsets of hypothalamic cells that controls wakefulness and rapid-eye movement (also called paradoxical) sleep using optogenetics in combination with high-density electrophysiology in freely-behaving mice. We further identified their connections with (and functional modulation of) other sleep-wake circuits throughout the brain. Although we and others have dissected important subcortical and cortical sleep-wake circuits in the brain, the precise mechanism bridging sub-cortical circuits to thalamic and cortical networks remains unclear. I hypothesizes that the thalamus represents a hub that integrates sleep-wake inputs of both subcortical and cortical origin into stable sleep-wake states, through topographically distinct sub-cortical inputs and temporally precise circuit dynamics (spiking pattern, coherence). To test this hypothesis, my experimental objectives are divided into three specific aims: 1) Identify the simultaneous cellular dynamics of thalamo-cortical network activity across sleep-wake states (Observational approach; Year 1-3) 2) Characterize the subcortical modulation of thalamic structures across sleep-wake states (Perturbational approach; Year 2-4) 3) Study the role of TRN/CMT circuits in sleep homeostasis and consciousness (Functional approach; Year 4-5) Completion of this project will provide a mechanistic perspective on sub-cortical, thalamo-cortical and cortical control of sleep-wake states, sleep homeostasis and consciousness in the mammalian brain.

1 915 000 €

Start date: 2017-06-01, End date: 2022-05-31

The properties of nanomaterials are essentially determined by their 3D structure. Electron tomography enables one to measure the morphology and composition of nanostructures in 3D, even at atomic resolution. Unfortunately, all these measurements are performed at room temperature and in ultra-high vacuum, which are conditions that are completely irrelevant for the use of nanoparticles in real applications! Moreover, nanoparticles often have ligands at their surface, which form the interface to the environment. These ligands are mostly neglected in imaging, although they strongly influence the growth, thermal stability and drive self-assembly. I will develop innovative and quantitative 3D characterisation tools, compatible with the fast changes of nanomaterials that occur in a realistic thermal and gaseous environment. To visualise surface ligands, I will combine direct electron detection with novel exit wave reconstruction techniques. Tracking the 3D structure of nanomaterials in a relevant environment is extremely challenging and ambitious. However, our preliminary experiments demonstrate the enormous impact. We will be able to perform a dynamic characterisation of shape changes of nanoparticles. This is important to improve thermal stability during drug delivery, sensing, data storage or hyperthermic cancer treatment. We will provide quantitative 3D measurements of the coordination numbers of the surface atoms of catalytic nanoparticles and follow the motion of individual atoms live during catalysis. By visualising surface ligands, we will understand their fundamental influence on particle shape and during self-assembly. This program will be the start of a completely new research line in the field of 3D imaging at the atomic scale. The outcome will certainly boost the design and performance of nanomaterials. This is not only of importance at a fundamental level, but is a prerequisite for the incorporation of nanomaterials in our future technology.

2 000 000 €

Start date: 2019-05-01, End date: 2024-04-30

Our memory system is optimised for remembering the exceptional over the mundane. We remember better those events that violate predictions generated by the prevailing context, particularly because of surprise or emotional impact. Understanding how we form and retrieve long-term memories for important or salient events is critical for combating the rapidly growing incidence of pathologies associated with memory dysfunction with huge socio-econonomic burden. Human lesion and non-invasive functional imaging data, motivated by findings from animal models, have identified subcortical structures that are critical for upregulating hippocampal function during salient event memory. However, mechanistic understanding of these processes in humans remains scarce, and requires better experimental approaches such as direct intracranial recordings from, and focal electrical stimulation of, these subcortical structures. This project will characterise human subcortico-cortical neuronal circuit dynamics associated with enhanced episodic memory for salient stimuli by studying direct recordings from human hippocampus, amygdala, nucleus accumbens, ventral midbrain and cortex. Within this framework, I will elucidate the electrophysiological mechanisms underlying amygdala-hippocampal-cortical coupling that lead to better memory for emotional stimuli, extend the hippocampal role in detecting unpredicted stimuli to define its role in orchestrating cortical dynamics in unpredictable contexts, and discover the neuronal response profile of the human mesolimbic dopamine system during salient stimulus encoding. The predicted results, based on my own preliminary data, will offer several conceptual breakthroughs, particularly regarding hippocampal function and the role of dopaminergic ventral midbrain in memory. The knowledge gained from this project is a fundamental requirement for designing therapeutic interventions for patients with memory deficits and other neuropsychiatric disorders.

2 000 000 €

Start date: 2019-05-01, End date: 2024-04-30