ERC FUNDED PROJECTS

Virtual reality, augmented reality and mixed reality are beginning to transform the way we explore and acquire information from the macroscopic world around us. At the same time, recent advances in holographic microscopy are providing new tools for the 3D imaging of physical and biological phenomena occurring at the micron scale. Project ADMIRE will combine this two emerging technologies into the first prototype of an AugmenteD MIcro-REality system for the immersive exploration and the quantitative analysis of three-dimensional processes at the micron scale. The core of the proposed system will be the three-axis holographic microscope (3DHM) developed within the ERC Project SMART to investigate fast 3D dynamics of swimming bacteria. ADMIRE project will transform 3DHM from a laboratory technique, targeted to a specific application and operated by highly specialised researchers into a general purpose instrument composed of a compact add-on module for commercial optical microscopes and a virtual reality interface allowing for a direct and intuitive use. Through the ADMIRE Holographic Microscope (ADMIRE-HM) the user will be “shrunk” a million times and virtually sent into a live 3D reconstruction of the real microscopic world contained in the glass slide. There he will find himself surrounded by micro-particles or moving cells that could be inspected from multiple directions and characterized by shape parameters (e.g. size, volume, aspect-ratio) or dynamical features (e.g. flagellar motility, sedimentation velocity, transport in a flow) obtained by means of simple and direct gestures. The expected outcome of the project is to bring to a development stage TRL 6-7 a technology that could change the way we experience the microscopic world in basic research, biomedical applications and education.

150 000 €

Start date: 2017-11-01, End date: 2019-04-30

AGEnTh is an interdisciplinary proposal which aims at theoretically investigating atomic many-body systems (cold atoms and trapped ions) in close connection to concepts from quantum information, condensed matter, and high energy physics. The main goals of this programme are to: I) Find to scalable schemes for the measurements of entanglement properties, and in particular entanglement spectra, by proposing a shifting paradigm to access entanglement focused on entanglement Hamiltonians and field theories instead of probing density matrices; II) Show how atomic gauge theories (including dynamical gauge fields) are ideal candidates for the realization of long-sought, highly-entangled states of matter, in particular topological superconductors supporting parafermion edge modes, and novel classes of quantum spin liquids emerging from clustering; III) Develop new implementation strategies for the realization of gauge symmetries of paramount importance, such as discrete and SU(N)xSU(2)xU(1) groups, and establish a theoretical framework for the understanding of atomic physics experiments within the light-from-chaos scenario pioneered in particle physics. These objectives are at the cutting-edge of fundamental science, and represent a coherent effort aimed at underpinning unprecedented regimes of strongly interacting quantum matter by addressing the basic aspects of probing, many-body physics, and implementations. The results are expected to (i) build up and establish qualitatively new synergies between the aforementioned communities, and (ii) stimulate an intense theoretical and experimental activity focused on both entanglement and atomic gauge theories. In order to achieve those, AGEnTh builds: (1) on my background working at the interface between atomic physics and quantum optics from one side, and many-body theory on the other, and (2) on exploratory studies which I carried out to mitigate the conceptual risks associated with its high-risk/high-gain goals.

1 055 317 €

Start date: 2018-05-01, End date: 2023-04-30

Real-world optimization problems pose major challenges to algorithmic research. For instance, (i) many important problems are believed to be intractable (i.e. NP-hard) and (ii) with the growth of data size, modern applications often require a decision making under {\em incomplete and dynamically changing input data}. After several decades of research, central problems in these domains have remained poorly understood (e.g. Is there an asymptotically most efficient binary search trees?) Existing algorithmic techniques either reach their limitation or are inherently tailored to special cases. This project attempts to untangle this gap in the state of the art and seeks new interplay across multiple areas of algorithms, such as approximation algorithms, online algorithms, fixed-parameter tractable (FPT) algorithms, exponential time algorithms, and data structures. We propose new directions from the {\em structural perspectives} that connect the aforementioned algorithmic problems to basic questions in combinatorics. Our approaches fall into one of the three broad schemes: (i) new structural theory, (ii) intermediate problems, and (iii) transfer of techniques. These directions partially build on the PI's successes in resolving more than ten classical problems in this context. Resolving the proposed problems will likely revolutionize our understanding about algorithms and data structures and potentially unify techniques in multiple algorithmic regimes. Any progress is, in fact, already a significant contribution to the algorithms community. We suggest concrete intermediate goals that are of independent interest and have lower risks, so they are suitable for Ph.D students.

1 411 258 €

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

Dysregulation of capillary permeability is a severe problem in critically ill patients, but the mechanisms involved are poorly understood. Further, there are no targeted therapies to stabilize leaky vessels in various common, potentially fatal diseases, such as systemic inflammation and sepsis, which affect millions of people annually. Although a multitude of signals that stimulate opening of endothelial cell-cell junctions leading to permeability have been characterized using cellular and in vivo models, approaches to reverse the harmful process of capillary leakage in disease conditions are yet to be identified. I propose to explore a novel autocrine endothelial permeability regulatory system as a potentially universal mechanism that antagonizes vascular stabilizing ques and sustains vascular leakage in inflammation. My group has identified inflammation-induced mechanisms that switch vascular stabilizing factors into molecules that destabilize vascular barriers, and identified tools to prevent the barrier disruption. Building on these discoveries, my group will use mouse genetics, structural biology and innovative, systematic antibody development coupled with gene editing and gene silencing technology, in order to elucidate mechanisms of vascular barrier breakdown and repair in systemic inflammation. The expected outcomes include insights into endothelial cell signaling and permeability regulation, and preclinical proof-of-concept antibodies to control endothelial activation and vascular leakage in systemic inflammation and sepsis models. Ultimately, the new knowledge and preclinical tools developed in this project may facilitate future development of targeted approaches against vascular leakage.

1 999 770 €

Start date: 2018-05-01, End date: 2023-04-30

Spontaneous protein crystallization is a rare event in biology. Eosinophilic inflammation such as seen in the airways in asthma, chronic rhinosinusitis and helminth infection is however accompanied by accumulation of large amounts of extracellular Charcot-Leyden crystals. These are made of Galectin-10, a protein of unknown function produced by eosinophils, hallmark cells of type 2 immunity. In mice, eosinophilic inflammation is also accompanied by protein crystal build up, composed of the chitinase-like proteins Ym1 and Ym2, produced by alternatively activated macrophages. Here we challenge the current view that these crystals are just markers of eosinophil demise or macrophages activation. We hypothesize that protein crystallization serves an active role in immunoregulation of type 2 immunity. On the one hand, crystallization might turn a harmless protein into a danger signal. On the other hand, crystallization might sequester and eliminate the physiological function of soluble Galectin-10 and Ym1, or prolong it via slow release elution. For full understanding, we therefore need to understand the function of the proteins in a soluble and crystalline state. Our program at the frontline of immunology, molecular structural biology and clinical science combines innovative tool creation and integrative research to investigate the structure, function, and physiology of galectin-10 and related protein crystals. We chose to study asthma as the crystallizing proteins are abundantly present in human and murine disease. There is still a large medical need for novel therapies that could benefit patients with chronic steroid-resistant disease, and are alternatives to eosinophil-depleting antibodies whose long term effects are unknown.

2 499 846 €

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

I will address the fundamental question of which is the role of neuron activity and plasticity in information elaboration and storage in the brain. I, together with an interdisciplinary team, will develop a hybrid neuro-morphic computing platform. Integrated photonic circuits will be interfaced to both electronic circuits and neuronal circuits (in vitro experiments) to emulate brain functions and develop schemes able to supplement (backup) neuronal functions. The photonic network is based on massive reconfigurable matrices of nonlinear nodes formed by microring resonators, which enter in regime of self-pulsing and chaos by positive optical feedback. These networks resemble human brain. I will push this analogy further by interfacing the photonic network with neurons making hybrid network. By using optogenetics, I will control the synaptic strengthen-ing and the neuron activity. Deep learning algorithms will model the biological network functionality, initial-ly within a separate artificial network and, then, in an integrated hybrid artificial-biological network. My project aims at: 1. Developing a photonic integrated reservoir-computing network (RCN); 2. Developing dynamic memories in photonic integrated circuits using RCN; 3. Developing hybrid interfaces between a neuronal network and a photonic integrated circuit; 4. Developing a hybrid electronic, photonic and biological network that computes jointly; 5. Addressing neuronal network activity by photonic RCN to simulate in vitro memory storage and retrieval; 6. Elaborating the signal from RCN and neuronal circuits in order to cope with plastic changes in pathologi-cal brain conditions such as amnesia and epilepsy. The long-term vision is that hybrid neuromorphic photonic networks will (a) clarify the way brain thinks, (b) compute beyond von Neumann, and (c) control and supplement specific neuronal functions.

2 499 825 €

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

In BIORECAR I will develop a new breakthrough multifunctional biomaterial-based platform for myocardial regeneration after myocardial infarction, provided with biochemical cues able to enhance the direct reprogramming of human cardiac fibroblasts into functional cardiomyocytes. My expertise in bioartificial materials and biomimetic scaffolds and the versatile chemistry of polyurethanes will be the key elements to achieve a significant knowledge and technological advancement in cell reprogramming therapy, opening the way to the future translation of the therapy into the clinics. I will implement this advanced approach through the design of a novel 3D in vitro tissue-engineered model of human cardiac fibrotic tissue, as a tool for testing and validation, to maximise research efforts and reduce animal tests. I will adapt novel nanomedicine approaches I have recently developed for drug release to design innovative cell-friendly and efficient polyurethane nanoparticles for targeted reprogramming of cardiac fibroblasts. I will design an injectable bioartificial hydrogel based on a blend of a thermosensitive polyurethane and a natural component selected among a novel cell-secreted natural polymer mixture (“biomatrix”) recapitulating the complexity of cardiac extracellular matrix or one of its main protein constituents. Such multifunctional hydrogel will deliver in situ agents stimulating recruitment of cardiac fibroblasts together with the nanoparticles loaded with reprogramming therapeutics, and will provide biochemical signalling to stimulate efficient conversion of fibroblasts into mature cardiomyocytes. First-in-field biomaterials-based innovations introduced by BIORECAR will enable more effective regeneration of functional myocardial tissue respect to state-of-the art approaches. BIORECAR innovation is multidisciplinary in nature and will be accelerated towards future clinical translation through my clinical, scientific and industrial collaborations.

2 000 000 €

Start date: 2018-07-01, End date: 2023-06-30

What did politicians sound like before they were on the radio and television? The fascination with politicians’ vocal characteristics and quirks is often connected to the rise of audio-visual media. But in the age of the printed press, political representatives also had to ‘speak well’ – without recourse to amplification. Historians and linguists have provided sophisticated understandings of the discursive and aesthetic aspects of politicians’ language, but have largely ignored the importance of the acoustic character of their speech. CALLIOPE studies how vocal performances in parliament have influenced the course of political careers and political decision making in the 19th century. It shows how politicians’ voices helped to define the diverse identities they articulated. In viewing parliament through the lens of audibility, the project offers a new perspective on political representation by reframing how authority was embodied (through performances that were heard, rather than seen). It does so for the Second Chamber in Britain and France, and in dialogue with ‘colonial’ modes of speech in Kolkata and Algiers, which, we argue, exerted considerable influence on European vocal culture. The project devises an innovative methodological approach to include the sound of the human voice in studies of the past that precede acoustic recording. Adapting methods developed in sound studies and combining them with the tools of political history, the project proposes a new way to analyse parliamentary reporting, while also drawing on a variety of sources that are rarely connected to the history of politics. The main source material for the study comprise transcripts of parliamentary speech (official reports and renditions by journalists). However, the project also mobilizes educational, satirical and fictional sources to elucidate the convoluted processes that led to the cultivation, exertion, reception and evaluation of a voice ‘fit’ for nineteenth-century politics.

1 499 905 €

Start date: 2018-03-01, End date: 2023-02-28

The concept that any cell type, upon delivery of the right “cocktail” of transcription factors, can acquire an identity that otherwise it would never achieve, revolutionized the way we approach the study of developmental biology. In light of this, the discovery of induced pluripotent stem cells (IPSCs) and cell fate conversion approaches stimulated new research directions into human regenerative biology. However, the chance to successfully develop patient-tailored therapies is still very limited because reprogramming technologies are applied without a comprehensive understanding of the molecular processes involved. Here, I propose a multifaceted approach that combines a wide range of cutting-edge integrative genomic strategies to significantly advance our understanding of the regulatory logic driving cell fate decisions during human reprogramming to pluripotency. To this end, I will utilize single cell transcriptomics to isolate reprogramming intermediates, reconstruct their lineage relationships and define transcriptional regulators responsible for the observed transitions (AIM 1). Then, I will dissect the rules by which transcription factors modulate the activity of promoters and enhancer regions during reprogramming transitions, by applying synthetic biology and genome editing approaches (AIM 2). Then, I will adopt an alternative approach to identify reprogramming modulators by the analysis of reprogramming-induced mutagenesis events (AIM 3). Finally, I will explore my findings in multiple primary reprogramming approaches to pluripotency, with the ultimate goal of improving the quality of IPSC derivation (Aim 4). In summary, this project will expose novel determinants and yet unidentified molecular barriers of reprogramming to pluripotency and will be essential to unlock the full potential of reprogramming technologies for shaping cellular identity in vitro and to address pressing challenges of regenerative medicine.

1 497 250 €

Start date: 2018-03-01, End date: 2023-02-28

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

Owing to their visual essence and status as a popular, modern medium, comics – newspaper strips, comics magazines and graphic novels – provide valuable insight into the transformation of collective consciousness. This project advances the hypothesis that children in comics are distinctive embodiments of the complex experience of modernity, channeling and tempering modern anxieties and incarnating the freedom denied to adults. In testing this hypothesis, the project constructs the first intercultural history of children in European comics, tracing the changing conceptualizations of child protagonists in popular comics for both children and adults from the mid-19th century to the present. In doing so, it takes key points in European history as well as the history of comics into account. Assembling a team of six multilingual researchers, the project uses an interdisciplinary methodology combining comics studies and childhood studies while also incorporating specific insights from cultural studies (history of family life, history of public life, history of the body, affect theory and scholarship on the carnivalesque). This enables the project to analyze the transposition of modern anxieties, conceptualizations of childishness, child-adult power relations, notions of liberty, visualizations of the body, family life, school and public life as well as the presence of affects such as nostalgia and happiness in comics starring children. The project thus opens up a new field of research lying at the intersection of comics studies and childhood studies and illustrates its potential. In studying popular but often overlooked comics, the project provides crucial historical and analytical material that will shape future comics criticism and the fields associated with childhood studies. Furthermore, the project’s outreach activities will increase collective knowledge about comic strips, which form an important, increasingly visible part of cultural heritage.

1 452 500 €

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

Metal organic frameworks (MOFs) are recently considered as new fascinating nanoporous materials. MOFs have very large surface areas, high porosities, various pore sizes/shapes, chemical functionalities and good thermal/chemical stabilities. These properties make MOFs highly promising for gas separation applications. Thousands of MOFs have been synthesized in the last decade. The large number of available MOFs creates excellent opportunities to develop energy-efficient gas separation technologies. On the other hand, it is very challenging to identify the best materials for each gas separation of interest. Considering the continuous rapid increase in the number of synthesized materials, it is practically not possible to test each MOF using purely experimental manners. Highly accurate computational methods are required to identify the most promising MOFs to direct experimental efforts, time and resources to those materials. In this project, I will build a complete MOF library and use molecular simulations to assess adsorption and diffusion properties of gas mixtures in MOFs. Results of simulations will be used to predict adsorbent and membrane properties of MOFs for scientifically and technologically important gas separation processes such as CO2/CH4 (natural gas purification), CO2/N2 (flue gas separation), CO2/H2, CH4/H2 and N2/H2 (hydrogen recovery). I will obtain the fundamental, atomic-level insights into the common features of the top-performing MOFs and establish structure-performance relations. These relations will be used as guidelines to computationally design new MOFs with outstanding separation performances for CO2 capture and H2 recovery. These new MOFs will be finally synthesized in the lab scale and tested as adsorbents and membranes under practical operating conditions for each gas separation of interest. Combining a multi-stage computational approach with experiments, this project will lead to novel, efficient gas separation technologies based on MOFs.

1 500 000 €

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

Evidence of a growing disengagement of citizens from politics is multiplying. Electoral turnout reaches historically low levels. Anti-establishment and populist parties are on the rise. Fewer and fewer Europeans trust their representative institutions. In response, we have observed a multiplication of institutional reforms aimed at revitalizing representative democracy. Two in particular stand out: the delegation of some political decision-making powers to (1) selected citizens and to (2) selected experts. But there is a paradox in attempting to cure the crisis of representative democracy by introducing such reforms. In representative democracy, control over political decision-making is vested in elected representatives. Delegating political decision-making to selected experts/citizens is at odds with this definition. It empowers the non-elected. If these reforms show that politics could work without elected officials, could we really expect that citizens’ support for representative democracy would be boosted and that citizens would re-engage with representative politics? In that sense, would it be a cure for the crisis of representative democracy, or rather a curse? Our central hypothesis is that there is no universal and univocal healing (or harming) effect of non-elected politics on support for representative democracy. In order to verify it, I propose to collect data across Europe on three elements: (1) a detailed study of the preferences of Europeans on how democracy should work and on institutional reforms towards non-elected politics, (2) a comprehensive inventory of all actual cases of empowerment of citizens and experts implemented across Europe since 2000, and (3) an analysis of the impact of exposure to non-elected politics on citizens’ attitudes towards representative democracy. An innovative combination of online survey experiments and of panel surveys will be used to answer this topical research question with far-reaching societal implication.

1 981 589 €

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

The first direct detection of gravitational waves demonstrated that double black hole (BH) binaries exist, and can host surprisingly massive objects (> 20 solar masses). Most theoretical models do not predict the existence of such massive BHs, and the formation channels of BH binaries are essentially unconstrained. Dynamically formed BH binaries are the most elusive ones: current models either neglect them or study them in idealized systems. With DEMOBLACK, I will draw the first satisfactory picture of BH binary demography, by modeling realistic BH dynamics in a well-motivated cosmological context. I propose a novel approach for the study of BH dynamics: I will simulate the formation of BH binaries in star clusters self-consistently, starting from the hydrodynamics of the parent molecular cloud and accounting for the impact of stellar evolution, feedback, and dynamics on BH binaries. The key tool of DEMOBLACK is SEVN, my new population-synthesis code. With SEVN, I predicted the formation of massive BHs from metal-poor stars, before the first direct detection of gravitational waves. I will interface SEVN with a hydrodynamical code and with an N-body code, to study the formation of BH binaries self-consistently. I will then model the history of BH binaries across cosmic time, accounting for the evolution of metallicity. This novel approach is decisive to break degeneracies between dynamically formed and primordial BH binaries, and to make predictions for future observations by ground-based and space-borne gravitational wave interferometers.

1 994 764 €

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

The connections between the circulation of news of extreme events, the making of influential narratives of collective traumas and the development of emergency response policies lie at the heart of this research proposal, which focuses on four Southern European areas: Catalonia, Naples, Sicily and Valencia, from the 16th to the 18th century. How did accounts and individual memories of extreme events amount to authoritative interpretations? In which ways, and to what extent, did the latter orient collective behaviours and the recovery process, in both the short and the long term? Starting from the assumption that human relations are enhanced by the increased levels of socialisation that commonly occur in the aftermath of shocking events, which trigger the sharing of information, opinions and memories; and that the emotional impact of such events is likely to create a public opinion that draws attention to government’s action; the research proposal aims to contribute new insights into these issues by adopting an original methodology, developed across a variety of disciplines, including Cultural and Social History, Textual Criticism, Philology and Anthropology. Moreover, it will adopt a transnational perspective: since the selected regions belonged to the Spanish Monarchy, the development of practices and polices aimed to respond to disruption depended not only on the specific social and cultural features of local societies, but also on the circulation of political and technical staff, as well as on the sharing of knowledge, experiences and policy models, among the various areas of the Empire and its colonies. Studying the information exchange in the aftermath of disasters and the formation of an imagery of extraordinary events, will allow a comprehensive perspective on the policies and practices adopted by early modern societies to manage uncertainty, and on the potential impact that such narratives could have on the renegotiation of political and social relations.

1 481 813 €

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

Despite the ubiquity of expansion and retraction dynamics of flowing streams, the large majority of biogeochemical and hydrological studies conceive river networks as static elements of the landscape, and a coherent framework to quantify nature and extent of drainage network dynamics is lacking. The implications of this phenomenon extend far beyond hydrology and involve key ecological and biogeochemical function of riparian corridors. The proposed research project will move beyond the traditional paradigm of static river networks by unravelling, for the first time, physical causes and biogeochemical consequences of stream dynamics. In particular, the project will undertake the following overarching scientific questions: 1) what are the climatic and geomorphic controls on the expansion/contraction of river networks? 2) what is the length of temporary streams and what is their impact on catchment-scale biogeochemical processes and stream water quality across scales? These challenging issues will be addressed by developing a novel theoretical framework complemented by extensive field observations within four representative sites along a climatic gradient in the EU. Field measurements will include long-term weekly mapping of the active drainage network and daily hydro-chemical data across scales. The experimental dataset will be used to develop and inform a set of innovative modelling tools, including an analytical framework for the description of spatially explicit hydrologic dynamics driven by stochastic rainfall and a modular hydro-chemical model based on the concept of water age, able to account for the variable connectivity among soil, groundwater and channels as induced by stream network dynamics. The project will open new avenues to quantify freshwater carbon emissions - crucially dependent on the extent of ephemeral streams - and it will provide a robust basis to identify temporary rivers and maintain their biogeochemical function in times of global change.

1 999 758 €

Start date: 2018-05-01, End date: 2023-04-30

Future data-driven modelling is increasingly challenging for many systems due to higher complexity levels, such as in energy systems, environmental and climate modelling, traffic and transport, industrial processes, health, safety, and others. This requires powerful concepts and frameworks that enable the design of high quality predictive models. In this proposal E-DUALITY we will explore and engineer the potential of duality principles for future data-driven modelling. An existing example illustrating the important role of duality in this context is support vector machines, which possess primal and dual model representations, in terms of feature maps and kernels, respectively. Within this project, besides using existing notions of duality that are relevant for data-driven modelling (e.g. Lagrange duality, Legendre-Fenchel duality, Monge-Kantorovich duality), we will also explore new ones. Duality principles will be employed for obtaining a generically applicable framework with unifying insights, handling different system complexity levels, optimal model representations and designing efficient algorithms. This will require taking an integrative approach across different research fields. The new framework should be able to include e.g. multi-view and multiple function learning, multiplex and multilayer networks, tensor models, multi-scale and deep architectures as particular instances and to combine several of such characteristics, in addition to simple basic schemes. It will include both parametric and kernel-based approaches for tasks as regression, classification, clustering, dimensionality reduction, outlier detection and dynamical systems modelling. Higher risk elements are the search for new standard forms in modelling systems with different complexity levels, matching models and representations to system characteristics, and developing algorithms for large scale applications within this powerful new framework.

2 492 500 €

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

In this proposal we plan to bring to a development stage TRL 3 an electro-optical device working at room temperature and based on polaritons (an hybrid photon-exciton particle) made of 2D perovskites and of an optical surface mode in a Distributed Bragg Reflector waveguide. Such a device could lead to extremely compact and ultrafast electro-optical modulators that can be fully integrated in a microchip to allow for fast signal communications between each peripheral component of a processor. As a matter of fact one of the major bottlenecks in processing speed is caused by retardations and dissipations in the interconnections between the CPU and the memory elements as well as other interconnect functions. Conversion of the electrical signal into an optical one can allow for faster and more efficient processing. Our prototype can allow for switching and routing of guided optical beams via electrical signals using the intrinsic nonlinearities of the hybrid photon-exciton states.

149 406 €

Start date: 2017-10-01, End date: 2019-03-31

ENERGYA will improve our understanding of how energy and energy services can be used by households and industries to adapt to the risk posed by climate change. Specifically, the project will develop an interdisciplinary and scalable research framework integrating data and methods from economics with geography, climate science, and integrated assessment modelling to provide new knowledge concerning heterogeneity in energy use across countries, sectors, socioeconomic conditions and income groups, and assess the broad implications adaptation-driven energy use can have on the economy, the environment, and welfare. The key novelty of ENERGYA is to link energy statistics and energy survey data with high spatial resolution data from climate science and remote sensing, including high-resolution spatial data on meteorology, population and economic activity distribution, electrification, and the built environment. ENERGYA has three main objectives. First, it will produce novel statistical and econometric analyses for OECD and major emerging countries (Brazil, Mexico, India, and Indonesia) to shed light on the underlying mechanisms driving energy use. Second, it will infer future potential impacts from long-run climate and socioeconomic changes building on historical empirical evidence. Third, it will analyse the macro and distributional implications of adaptation-driven energy use with an economy-energy model characterising the distribution of energy use dynamics across and within countries. Given the central role of energy as multiplier for socioeconomic development and as enabling condition for climate resilience, the research proposed in ENERGYA will result in timely insights for the transition towards sustainability described by the Sustainable Development Goals adopted by the United Nations as well as the Paris International Climate Agreement.

1 495 000 €

Start date: 2018-03-01, End date: 2023-02-28

"Given the alarming progression of chronic and relapsing infections in the last decades, and the even more alarming predictions for the upcoming years, it is urgent for chemists to be able to provide new molecular tools to study, and ultimately solve, these complex biological problems. Bacterial persisters are an elusive ""dormant"" phenotype that play a pivotal role in chronic infections, with mechanisms that remain to be fully unravelled. Current knowledge suggests that bacterial persisters are not genetically resistant to antibiotic treatment; they simply appear to shut down through a cascade of biochemical events called the stringent response (SR), becoming insensitive to current drugs. This subpopulation remains unaffected during the time of pharmacological treatment and represents a reservoir that sustains pathogen survival and resurgence. The goal of this project is to fill the knowledge gap between persisters formation and infection eradication, providing the community with potent and selective small molecular tools that can be used to challenge complementary survival mechanisms. I will adopt a combined approach targeting a specific cellular trigger of the persister phenotype with small molecules designed ad hoc in order to switch it off. The target is a bacterial protein involved in the SR cascade, whose activity is proposed to be allosterically regulated. Coordination propensity analysis of the dynamic behaviour of the target will highlight regulation sites exploitable to modulate and control the protein activity. Structure-based design, virtual fragment screening and chemical synthesis will operate in synergy. Experimental screening methodologies intrinsically rich in structural information, such as those based on NMR spectroscopy, will be privileged. The overarching goal is to identify molecules able to prevent the insurgence of the ""dormant"" drug-tolerant state and, possibly, revert the persisters already present to the ""awake"" drug-sensitive phenotype. "

1 500 000 €

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

Given the crucial importance of European Parliament’s party groups to democratic representation in the European Union, it is surprising that there is limited empirical and theoretical understanding that relates to how they conceive of gender, gender hierarchies and gendered relations, or how they seek to address gender inequalities. Nor do we know what the conditions are for increasing a gender equal democracy in the EU in the face of the current political context shaped by political crises. This project aims to provide a systematic analysis of the gendered policies and practices of European party politics. The research comprises a comparative study of the eight European Parliament (EP) party groups and generates empirical findings about the significance of gender in the current party political transformations in Europe. Further potential lies in the key methodological innovation whereby the proposed project links informal institutions and discourses to affects and emotions, generating research designs with which the persistence of gender inequalities can be analysed more thoroughly than current gender and politics research allows. More nuanced conceptualizations, and theories about inclusive representation, gender justice and democracy at the transnational level, are a likely consequence of adopting an innovative methodological approach where empirical findings inform the theoretical level. Therefore, the project may have a high societal impact as it speaks directly to the current political crises in Europe, and provides an understanding of their gendered underpinnings. Thus, the key ambition of this research project is: based on a thorough empirical understanding of gender and party politics at the European Parliament to build novel methodologies, concepts and theories about inclusive representation, gender justice and democracy.

1 976 482 €

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

This five-year project aims to generate a paradigm shift in the understanding of Graeco-Roman and Late Antique communication. Non-literary, ‘documentary’ texts from Ancient Egypt such as letters, petitions and contracts have provided and continue to provide a key witness for our knowledge of the administration, education, economy, etc. of Ancient Egypt. This project argues that since documentary texts represent originals, their external characteristics should also be brought into the interpretation: elements such as handwriting, linguistic register or writing material transmit indirect social messages concerning hierarchy, status, and power relations, and can therefore be considered ‘semiotic resources’. The project’s driving hypothesis is that communicative variation – variation that is functionally insignificant but socially significant (e.g. there are ~ there’s ~ it’s a lot of people) – enables the expression of social meaning. The main aim of this project is to analyse the nature of this communicative variation. To this end, a multidisciplinary team of six researchers (one PI, one post-doc, and four PhD’s) will apply recent insights form socio-semiotic and socio-linguistic theory to a corpus of Graeco-Roman and Late Antique documentary texts (I – VIII AD) by means of a three-level approach: (i) an open-access database of annotated documentary texts will be created; (ii) the ‘semiotic potential’ of the different semiotic resources that play a role in documentary writing will be analysed; (iii) the interrelationships between the different semiotic resources will be studied. The project will have a significant scientific impact: (i) it will be the first to offer a holistic perspective towards the ‘meaning’ of documentary texts; (ii) the digital tool will open up new ways to investigate Ancient texts; (iii) it will make an important contribution to current socio-semiotic and socio-linguistic research; (iv) it will provide new insights about humans as social beings.

1 476 250 €

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

FLOS will focus on the metamorphoses of Greek Christian thought in Syriac (Aramaic) and Arabic in Late Antiquity, within the timeframe of the first millennium CE. Syriac Christianity was a pivotal mediator of culture in the Late Antique epistemic space, but is little-known today. FLOS aims to bring to light for the first time a body of highly relevant Syriac and Christian Arabic sources that have hardly ever been studied before. At the end of the millennium, in Islamic-ruled Syria, Mesopotamia, and Iran, Syriac Christians strived to define their religious identity. One of their strategies was the production of florilegia, i.e. anthologies that they used to excerpt and reinvent the patristic canon, a corpus of Greek Christian works of the 2nd–6th centuries shared by European and Middle Eastern Christian cultures. A Greco-centric bias has prevented scholars from viewing these florilegia as laboratories of cultural creativity. FLOS will reverse the state of the art through two groundbreaking endeavours: 1) open-access digital editions of a set of Syriac florilegia of the 8th–10th centuries; 2) a study of many neglected writings of Syriac and Christian Arabic authors of the 8th–11th centuries. These tremendously important writings drew from Syriac patristic florilegia to pinpoint topics like incarnation and the Trinity against other Christians or Islam, showing how patristic sources were used to create new knowledge for the entangled environment of the Abbasid era. FLOS will thus dramatically improve our understanding of the cultural dynamics of Late Antiquity; patristic Christianity will emerge as a bridge between the intellectual history of Europe and of the Middle East. By studying how this shared patrimony was transformed in situations of interreligious interaction, especially with Islam, FLOS will facilitate the comprehension of Europe’s current religious discourses, and the preservation of the endangered cultural heritage of the Syriac Christians.

1 343 175 €

Start date: 2018-03-01, End date: 2023-02-28

Recent global warming is acting across ecosystems and threatening biodiversity. Yet, due to slow responses, many biological communities are lagging behind warming of the macroclimate (the climate of a large geographic region). The buffering of microclimates near the ground measured in localized areas, arising from terrain features such as vegetation and topography, can explain why many species are lagging behind macroclimate warming. However, almost all studies ignore the effects of microclimatic buffering and key uncertainties still exist about this mechanism. Microclimates are particularly evident in forests, where understorey habitats are buffered by overstorey trees. In temperate forests, the understorey contains the vast majority of plant diversity and plays an essential role in driving ecosystem processes. The overall goal of FORMICA (FORest MICroclimate Assessment) is to quantify and understand the role of microclimatic buffering in modulating forest understorey plant responses to macroclimate warming. We will perform the best assessment to date of the effects of microclimates on plants by applying microtemperature loggers, experimental heating, fluorescent tubes and a large-scale transplant experiment in temperate forests across Europe. For the first time, plant data from the individual to ecosystem level will be related to microclimate along wide temperature gradients and forest management regimes. The empirical results will then be integrated in cutting-edge demographic distribution models to forecast plant diversity in temperate forests as macroclimate warms. FORMICA will provide the first integrative study on microclimatic buffering of macroclimate warming in forests. Interdisciplinary concepts and methods will be applied, including from climatology, forestry and ecology. FORMICA will reshape our current understanding of the impacts of climate change on forests and help land managers and policy makers to develop urgently needed adaptation strategies.

1 498 469 €

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

Accounting for vegetation structure – clumping of foliage into shoots or crowns – is the largest remaining challenge in modelling scattered and absorbed radiation in complex vegetation canopies such as forests. Clumping controls the radiation regime of forest canopies, yet it is poorly quantified. Currently, the communities working with vegetation structure and optical measurements do not have a common understanding of the concept. The FREEDLES project sets out to develop a universal method for quantifying clumping of foliage in forests based on detailed 3D structure and spectral reflectance data. Clumping will be linked to photon recollision probability, an exciting new development in the field of photon transport modelling. Photon recollision probability will, in turn, be used to develop a spectral scaling algorithm which will connect the spectra of vegetation at all hierarchical levels from needles and leaves to crowns, stands and landscapes. The spectral scaling algorithm will be validated with detailed reference measurements in both laboratory and natural conditions, and applied to interpret forest variables from satellite images at different spatial resolutions. The proposed approach is contrary to many other lines of current development where more complexity is favoured in canopy radiation models. If successful, the approach will significantly improve estimates of absorbed and scattered radiation fields in forests and retrieval results of forest biophysical variables from satellite data. Future applications can also be expected in global radiation and carbon balance estimation and in chlorophyll fluorescence models for forests. Most importantly, the spectral scaling model will open new horizons for our scientific understanding of photon-vegetation interactions.

1 963 590 €

Start date: 2018-05-01, End date: 2023-04-30

Research in logic and foundations of mathematics received an enormous impact through the incompleteness theorems that Kurt Gödel published in 1931. They are among the most iconic scientific achievements of the 20th century. These results led to the development of true formal systems and to the notions of formal languages and algorithmic computability that are connected to such names as Alonzo Church and Alan Turing. The said notions are the direct basis on which the first programming languages and computers were built two decades later. Thus, the present information society owes a - well hidden - debt to the theoretically oriented foundational research that sprung off from Gödel's results. Strangely enough, there are several thousand pages of notes by this foremost figure of logic that have remained almost completely untouched. Such a situation would be unthinkable in many other fields. Say, with modern physics, every effort would have been made if Einstein - even Gödel's colleague and friend at the Princeton Institute - had left behind such a patrimony! With Gödel, the difficulty lies in part in the fact that the work is written down in an obsolete, forgotten old German stenographic script called Gabelsberger, a true enigma for those interested in the contents. A second difficulty is the intrinsic logical complexity of the work. The central aim of the project is to make this work available to future generations of logicians and philosophers. The principal investigator is in a unique position of being able to read the Gabelsberger notes and to interpret their logical content: What they mean in a historical-foundational context, what their significance is for today's research problems in logic, and how they change the view of Gödel as one of the most original thinkers of a century.

2 132 993 €

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

A seminal concept in modern neuroscience is the plasticity of the developing and adult brain that underpins the organismic ability to adapt to the ever-changing environment and internal states. Conversely, recent studies indicate that ongoing sensory input seems not crucial to modulate the overall level of brain activity, which instead it is strongly determined by its intrinsic fluctuations. These observations raise a fundamental question: what is coded in the intrinsic activity? This project tests the hypothesis that intrinsic activity represents and maintains an internal model of the environment built through the integration of information from visual and bodily inputs. The bodily inputs represent the physical and functional interaction that our body establishes with the external environment. In this framework, the hand has a special role, as it represents the primary means of interaction with the environment. Do behavior and mental activity change as a function of the effector we use to interact with the external environment? In virtual settings, I test the resilience of the internal model to extreme manipulations of the body by replacing the hand with everyday tools. The hypothesis is that prior representations constrain novel behaviors and plastic changes of both intrinsic and task-related brain activities. This prediction is also tested on samples of acquired amputees. These subjects represent an interesting model because the hand loss might reflect loss of sensory representations and less constrain on task-related brain activation. Throughout a combination of behavioral approaches, methods and techniques ranging from kinematics to functional neuroimaging (fMRI and MEG) and virtual reality, this project provides insights on how the synergic activity of body and environment shapes behavior and neural activity. This grant might open novel opportunities for future developments of robotic-assisted technology and neuroprostheses.

1 494 662 €

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

Glaciers show a pattern of retreat at the global scale. Increasing areas are exposed and colonized by multiple organisms, but lack of global studies hampers a complete understanding of the future of recently deglaciated terrains. What will be the fate of these areas? How do animals, plants and microorganisms colonize them? How do they interact to perform successful colonization? Which are the climatic, geological and biogeographical processes determining colonization patterns? How does ecosystem functioning evolves through time? Until now, the complete reconstruction of soil communities was hampered by the complexity of identification of organisms, thus analyses at broad geographical and taxonomic scale have been so far impossible. IceCommunities will combine innovative methods and a global approach to boost our understanding of the evolution of ecosystems in recently deglaciated areas. I will investigate chronosequences ranging from recently deglaciated terrains to late successional stages of soil pedogenesis. Through environmental DNA metabarcoding I will identify species from multiple taxonomic groups (bacteria, fungi, protists, soil invertebrates, plants), to obtain a complete reconstruction of biotic communities along glacier forelands over multiple mountain areas across the globe. This will allow measuring the rate of colonization at an unprecedented detail. Information on assemblages will be combined with analyses of soil, landscape and climate to identify the drivers of community changes. I will also identify the impact of eco-geographical factors (climate, regional pool of potential colonizers) on colonization. Analysis of functional traits will allow reconstructing how functional diversity emerges during community formation, and how it scales to the functioning of food webs. IceCommunities will help to predict the future development of these increasingly important ecosystems, providing a supported rationale for the appropriate management of these areas

1 845 773 €

Start date: 2018-04-01, End date: 2023-03-31

Impact investing is a major emerging phenomenon in global finance that promises to reconcile capitalism with sustainability. It is increasingly embraced by governments, civil society and the private sector in the Global North and South to solve social and environmental problems. The combined crises of climate change, inequality and mass migration in a context of economic austerity have spurred cross-sectoral impact investing partnerships in areas such as green infrastructure, women’s entrepreneurship, agroecology, refugee support and disease prevention. This burgeoning $200bn market promises flexible, holistic and profitable paths to sustainability, attracting major philanthropic organisations and institutional investors boasting fresh ethical and responsible mandates. Is impact investing merely a new frontier for capitalism, or does it represent a revolutionary chapter in global history? Will it benefit communities better than conventional development programmes? The time to answer these questions is now, as impact investing is still in its infancy and the first green and social stock exchanges are opening around the world. IMPACT HAU is an innovative, critical and comparative anthropological study of the moral and political dimensions of impact investing. Inspired by Marcel Mauss’s classic use of the Maori concept of hau, the ‘spirit of the gift’, it focuses on the designers, traders and beneficiaries of impact bonds to produce an empirically driven analysis of the multiple moral orders within contemporary capitalism. Six ethnographic case studies will provide grounded, detailed accounts of the design and implementation of impact investing in Africa, Asia, Europe and the Americas. These will support a critical appraisal of the current consensus among global policymakers and business leaders giving markets a determining role in the ecological transition, testing the theories of sustainability that underpin hopes for a socially inclusive green economy.

1 999 999 €

Start date: 2019-02-01, End date: 2024-01-31

Tissue Engineering (TE) refers to the branch of medicine that aims to replace or regenerate functional tissue or organs using man-made living implants. As the field is moving towards more complex TE constructs with sophisticated functionalities, there is a lack of dedicated in vitro devices that allow testing the response of the complex construct as a whole, prior to implantation. Additionally, the knowledge accumulated from mechanistic and empirical in vitro and in vivo studies is often underused in the development of novel constructs due to a lack of integration of all the data in a single, in silico, platform. The INSITE project aims to address both challenges by developing a new mesofluidics set-up for in vitro testing of TE constructs and by developing dedicated multiscale and multiphysics models that aggregate the available data and use these to design complex constructs and proper mesofluidics settings for in vitro testing. The combination of these in silico and in vitro approaches will lead to an integrated knowledge-rich mesofluidics system that provides an in vivo-like time-varying in vitro environment. The system will emulate the in vivo environment present at the (early) stages of bone regeneration including the vascularization process and the innate immune response. A proof of concept will be delivered for complex TE constructs for large bone defects and infected fractures. To realize this project, the applicant can draw on her well-published track record and extensive network in the fields of in silico medicine and skeletal TE. If successful, INSITE will generate a shift from in vivo to in vitro work and hence a transformation of the classical R&D pipeline. Using this system will allow for a maximum of relevant in vitro research prior to the in vivo phase, which is highly needed in academia and industry with the increasing ethical (3R), financial and regulatory constraints.

2 161 750 €

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

Disorders of the central nervous system (CNS) contribute almost 800 billion euros in annual European healthcare costs. New compounds, effective in animal models, hardly work in humans, mostly due to the inability to cross the Brain Blood Barrier (BBB). In these conditions cost-effective tools to alter BBB and, more generally, endothelial layer permeability is desirable before proceeding to expensive and time-consuming animal studies. INVICTUS (IN VItro Cavitation Through UltraSound) originates within the ERC-AdG project Bubbles from Inception to Collapse (BIC) and concerns the development of a biomimetic micro-fluidic platform to be made turnkey available to biologists, clinicians and pharmacologists. The integrated platform exploits endothelial layer permeability enhancement by cavitation bubbles and provides an integrated, low cost platform to develop cavitation enhanced drug delivery under well controlled and reproducible conditions. Its potential is significant, given the well known societal and economical impact of degenerative diseases and the enormous investment and the long times of pre-clinical trials, as confirmed by a leading company operating in the field. Limiting/avoiding animal experimentation has an evident ethical impact and is associated with substantial economic savings and organisational simplification. In few words, micro-bubbles injected into the bloodstream undergo volume oscillations under localised ultrasound irradiation, with local reversible permeability enhancement of the endothelium. Already pursed in in vivo animal models, this approach is extended here to a high-fidelity, in vitro biomimetic device that will bring to market new crucial features such as the three-dimensional geometry of realistic-size vascular channels featuring an actual endothelial barrier, the correct perfusion rate, the appropriate physiological shear stress exerted on the endothelial cells and the ability to reproduce biochemical interactions between different, healthy and diseased, tissues.

150 000 €

Start date: 2017-12-01, End date: 2019-05-31

The main research question of the study is: How and why do some European citizens generate a populist and Islamophobist discourse to express their discontent with the current social, economic and political state of their national and European contexts, while some members of migrant-origin communities with Muslim background generate an essentialist and radical form of Islamist discourse within the same societies? The main premise of this study is that various segments of the European public (radicalizing young members of both native populations and migrant-origin populations with Muslim background), who have been alienated and swept away by the flows of globalization such as deindustrialization, mobility, migration, tourism, social-economic inequalities, international trade, and robotic production, are more inclined to respectively adopt two mainstream political discourses: Islamophobism (for native populations) and Islamism (for Muslim-migrant-origin populations). Both discourses have become pivotal along with the rise of the civilizational rhetoric since the early 1990s. On the one hand, the neo-liberal age seems to be leading to the nativisation of radicalism among some groups of host populations while, on the other hand, it is leading to the islamization of radicalism among some segments of deprived migrant-origin populations. The common denominator of these groups is that they are both downwardly mobile and inclined towards radicalization. Hence, this project aims to scrutinize social, economic, political and psychological sources of the processes of radicalization among native European youth and Muslim-origin youth with migration background, who are both inclined to express their discontent through ethnicity, culture, religion, heritage, homogeneity, authenticity, past, gender and patriarchy. The field research will comprise four migrant receiving countries: Germany, France, Belgium, and the Netherlands, and two migrant sending countries: Turkey and Morocco.

2 276 125 €

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

One main objective of our ERC Advanced Grant project (InMec, No 341131) was to determine how cancer stem cells (CSCs) contribute to tumour growth, and the relative impact of quiescent versus proliferative CSCs. In Acute Myeloid Leukaemia (AML), our results strongly suggest that quiescent leukaemia stem cells are critical for leukaemia maintenance and relapse after treatments. AML is an aggressive and frequently fatal hematologic malignancy. It is usually sensitive to chemotherapy at its onset, leading to disease remission in most patients; however, the majority of patient will later relapse and eventually die. Notably, leukaemia stem cells are often resistant to chemotherapy. We will use our innovative phage-display antibody screening platform to generate antibodies against AMLs. The screening will be performed directly on human AMLs growing in vivo, using an innovative mouse xenotransplantation model followed by an NGS-based antibody selection procedure. We plan to isolate antibodies that selectively recognize leukaemia stem cells, either quiescent or proliferating. Our primary goal is to develop novel therapeutic antibodies for the treatment of AMLs. This project will also indirectly confirm the hypothesis that leukaemia stem cells are the real fuel of the disease. We expect that this project will lead to quick and cheap identification, cloning and validation of human recombinant antibodies towards against AML leukemic stem cells. The use of phage display technology to isolate leukemic stem cell-specific human recombinant antibodies is to our knowledge unprecedented. The development of candidate antibodies against AMLs will be accompanied by the promotion of commercial/exploitation activities such as market and competition analyses, intellectual property management, and product and business development through the activities of our partner TTFactor.

150 000 €

Start date: 2018-01-01, End date: 2019-06-30

Laser Ablation (LA) was extensively investigated for its benefits as minimally invasive thermal therapy for tumor. Despite the LA pros as potential alternative to surgical resection (e.g., use of small fiber optics, echo-endoscope procedures and image-guidance without artifact), the lack of tools for safe and patient-specific treatment restrained its clinical use. LASER OPTIMAL offers a renaissance to LA for the practical management of challenging tumors (e.g., pancreatic cancer): it investigates and develops integrated solutions to achieve an effective and selective LA, that thermally destroys the whole tumor mass, while spearing the normal tissue around. The excellent ambition of LASER OPTIMAL is to achieve and merge: a) biocompatible nanoparticles (BNPs) injected in the tumor, to enhance the selective absorption of laser light; b) patient-specific anatomy of tumor and its surrounding, extracted from clinical images, to retrieve the optimal laser settings; c) accurate, fast and real-time heat-transfer model to simulate laser-tissue-BNPs interaction, predict and visualize the treatment dynamics; d) real-time temperature measurement system to monitor LA effects, account for unpredictable physiological events and tune the settings (closed-loop). The design of ex vivo and in vivo animal tests allows assessing the system performances and driving the possible workflow re-design. Finally, human trials are envisaged to prove the significant impact of the LASER OPTIMAL paradigm. The collaboration of researchers, engineers and clinicians will drive the use of this innovative strategy in clinical routine. The research on the patient-specific system for the mini-invasive tumors removal, and the ground-breaking insights on clinical use of BNPs will strongly impact on EU healthcare system and society, by creating a novel product. This paradigm is also embeddable in existing system of industrial partner, extendable to other procedures, thus able to encourage a dedicated market.

1 499 575 €

Start date: 2018-05-01, End date: 2023-04-30

Visual awareness affords flexibility and experiential richness, and its loss following brain damage has devastating effects. However, patients with blindness following cortical damage may retain visual functions, despite visual awareness is lacking (blindsight). But, how can we translate non-conscious visual abilities into conscious ones after damage to the visual cortex? To place our understanding of visual awareness on firm neurobiological and mechanistic bases, I propose to integrate human and monkey neuroscience. Next, I will translate this wisdom into evidence-based clinical intervention. First, LIGHTUP will apply computational neuroimaging methods at the micro-scale level, estimating population receptive fields in humans and monkeys. This will enable analyzing fMRI signal similar to the way tuning properties are studied in neurophysiology, and to clarify how brain areas translate visual properties into responses associated with awareness. Second, LIGHTUP leverages a behavioural paradigm that can dissociate nonconscious visual abilities from awareness in monkeys, thus offering a refined animal model of visual awareness. Applying behavioural-Dynamic Causal Modelling to combine fMRI and behavioral data, LIGHTUP will build up a Bayesian framework that specifies the directionality of information flow in the interactions across distant brain areas, and their causal role in generating visual awareness. In the third part, I will devise a rehabilitation protocol that combines brain stimulation and visual training to promote the (re)emergence of lost visual awareness. LIGHTUP will exploit non-invasive transcranial magnetic stimulation (TMS) in a novel protocol that enables stimulation of complex cortical circuits and selection of the direction of connectivity that is enhanced. This associative stimulation has been proven to induce Hebbian plasticity, and we have piloted its effects in fostering visual awareness in association with visual restoration training.

1 994 212 €

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

Low cost coherent light sources from nanoparticle array surface plasmon polariton systems Lasers are ubiquitous sources of coherent light used in technology and everyday life, from optical communications enabling the internet to the lasers used in manufacturing, medical care and information storage. Coherent light sources with a small footprint, that are ultrafast and low cost, have low energy consumption could be used in sensor, switch and biomedical applications. Based on recent results of the PI's ERC Advanced project, nanolasers (lasers operating below the diffraction limit) that utilize non-radiative, so-called dark states have recently been demonstrated with organic materials. We have also just achieved a Bose-Einstein condensate (BEC) of photons in a similar system, which produces coherent light like a laser, but its formation mechanism is different: thermalization followed by bosonic stimulation, instead of just stimulated emission as in a laser. Thus, the usage and operation conditions of a luminous BEC can be complementary to a laser. This project will make such novel nanoscale coherent light sources cheap enough to be used in practical applications and demonstrate their use for example in sensor systems.

149 895 €

Start date: 2018-06-01, End date: 2019-11-30

Atmospheric concentration of the strong greenhouse gas methane (CH4) is rising with an increased annual growth rate. Biosphere has an important role in the global CH4 budget, but high uncertainties remain in the strength of its different sink and source components. Among the natural sources, the contribution of vegetation to the global CH4 budget is the least well understood. Role of trees to the CH4 budget of forest ecosystems has long been overlooked due to the perception that trees do not play a role in the CH4 dynamics. Methanogenic Archaea were long considered as the sole CH4 producing organisms, while new findings of aerobic CH4 production in terrestrial vegetation and in fungi show our incomplete understanding of the CH4 cycling processes. Enclosure measurements from trees reveal that trees can emit CH4 and may substantially contribute to the net CH4 exchange of forests. The main aim of MEMETRE project is to raise the process-based understanding of CH4 exchange in boreal and temperate forests to the level where we can construct a sound process model for the soil-tree-atmosphere CH4 exchange. We will achieve this by novel laboratory and field experiment focusing on newly identified processes, quantifying CH4 fluxes, seasonal and daily variability and drivers of CH4 at leaf-level, tree and ecosystem level. We use novel CH4 flux measurement techniques to identify the roles of fungal and methanogenic production and transport mechanisms to the CH4 emission from trees, and we synthesize the experimental work to build a process model including CH4 exchange processes within trees and the soil, transport of CH4 between the soil and the trees, and transport of CH4 within the trees. The project will revolutionize our understanding of CH4 flux dynamics in forest ecosystems. It will significantly narrow down the high uncertainties in boreal and temperate forests for their contribution to the global CH4 budget.

1 908 652 €

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

Metastatic growth of cancer cells requires extracellular matrix (ECM) production. The current understanding is that transcription factors regulate ECM production and thus metastatic growth by increasing the expression of collagen prolyl 4-hydroxylase (CP4H). In contrast, we recently discovered that metabolism regulates CP4H activity independently of the known transcription factors. Specifically, we found that loss of pyruvate metabolism inhibits CP4H activity and consequently ECM–dependent breast cancer cell growth. Based on this discovery we propose the novel concept that metabolism regulates metastatic growth by increasing ECM production. In this project we will investigate the following questions: 1) What is the mechanism by which pyruvate regulates CP4H activity in breast cancer cells? To address this question we will investigate pyruvate metabolism and ECM production in 3D cultures of various breast cancer cell lines using 13C tracer analysis, metabolomics, and two-photon microscopy based ECM visualization. 2) How can this novel metabolic regulation be exploited to inhibit breast cancer-derived lung metastases growth? To address this question we will inhibit pyruvate metabolism in metastatic breast cancer mouse models using genetically modified cells and small molecules in combination with immuno- and chemotherapy. 3) How can this novel regulation be translated to different metastatic sites and cancers of different origin? To address this question we will determine the in vivo metabolism of breast cancer-, lung cancer-, and melanoma-derived liver and lung metastases (using metabolomics and 13C tracer analysis), and link it to ECM production (using two-photon microscopy based ECM visualization). With this project we will deliver a novel concept by which metabolism regulates metastatic growth. In a long-term perspective we expect that targeting this novel metabolic regulation will pave the way for an unexplored approach to treat cancer metastases.

2 000 000 €

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

What determines the patterns of international trade and the associated welfare effects? Can individual incentives to trade diverge from societal objectives? Should governments intervene to promote or restrict international transactions? Questions like these have recently gained new salience, in Europe and elsewhere, due to renewed protectionist pressures and resurgent nationalistic tendencies arising from diffuse disenchantment with globalization. The aim of the research project is to highlighting key dimensions along which the answers to these questions obtained from conventional trade models with homogenous firms should be revisited in the light of permanent pervasive firm heterogeneity. In particular, the project will pursue four specific objectives through four integrated work packages providing new insights on how firm heterogeneity affects: (1) the ability of markets to deliver allocative efficiency; (2) The design of optimal multilateral trade policies; (3) The comparative advantages of countries; (4) The capabilities of a country as an exporter. The first work package will investigate whether the allocative inefficiency (“misallocation”) determined by firm heterogeneity in the presence of pricing distortions is quantitatively relevant for a country’s aggregate economic performance, and whether economic integration reduces or exacerbates such misallocation. The second work package will develop the theoretical implications of firm heterogeneity for trade policy, with special emphasis on the cooperative design of optimal multilateral trade agreements aimed at maximizing the joint welfare of all trade partners. The third work package will study how country, sector and firm characteristics interact to determine countries’ responses to trade liberalization. The fourth work package will investigate the distinct role of firm heterogeneity in determining a country’s ability to export through the shape of the productivity distribution of its producers.

1 335 694 €

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

We aspire to build the smallest and most lightweight Raman spectrometer in the world, with a target size of 5x10x1 mm3 and a weight of only 0.1 g. The innovation builds on the combination of three key results of the ERC Advanced Grant project InSpectra (2011-2017): 1. Demonstration of Nanophotonic waveguide Enhanced Raman Spectroscopy (NERS); 2. Demonstration of a novel on-chip Fourier Transform Spectrometer (FTS); 3. Demonstration of the integration of III-V light sources on a silicon platform through bonding or transfer printing technologies. By using a standard CMOS process toolset for fabricating the Raman spectrometer, a cost-effective and high yield product can be guaranteed with a price level at least an order of magnitude lower than current commercial systems. The exceptional form factor of the spectrometer will generate a rich variety of innovative applications of Raman spectroscopy. A spectrometer this small can be implanted, incorporated in smartphones or smartwatches and fits into textiles, drones etc. In this ERC PoC project, we will build this miniature spectrometer and use it for the target application of detecting volatile organic compounds (VOC) for personal safety monitoring, both at work and at home.

149 609 €

Start date: 2018-01-01, End date: 2019-06-30

Autism spectrum disorders (ASD) comprise an early-onset neurodevelopmental syndrome primarily characterized by impairments in social perception, cognition and communication, and a restricted pattern of interests and behavior. Without any doubt, infants and children with ASD greatly benefit from early behavioral intervention, therefore an early detection and treatment of ASD has been placed as a major health care priority. Unfortunately, nowadays, ASD diagnosis occurs at 2.5-4 years of age. In my previous ERC AdG Project, I proved that inborn predispositions to visual social stimuli (i.e., face-like patterns, eye-gaze and biological motion) is different between newborns at high-risk for ASD (HR, younger siblings of affected children) and newborns at low-risk (LR). Significant predictors for HR newborns were obtained and an accurate biomarker was identified. Starting from this, the goal of MoViS Project (Mobile Visual Stimulation) will be to develop, for the very first time, a simple and innovative tool for early screening and monitoring of neonates social behaviour by means of visual stimulation. This is an innovative and a promising project because, behind providing an important contribution in expanding our current knowledge about the ontogenesis of the ASD, the possibility of targeting high-risk infants during the first days of their life, via a behavioral marker for social orienting, could allow for a new generation of early therapeutic interventions for rehabilitation, starting in a time when brain plasticity allows reorganization of cortical circuits.

149 936 €

Start date: 2018-05-01, End date: 2019-10-31

In our current society, therapeutic strategies against cancer suffer from dose-limiting toxicity, lack of specificity and high morbidity. To overcome this, the use of nanomaterials (NMs) is rising, where several NM formulations are undergoing clinical trials or are used in clinics where the NMs are used as drug delivery vehicles or as mediators in physical anticancer methods (e.g. hyperthermia), where to date, the success rate is limited due to low tumor targeting efficacy, lack of specificity and frequent re-use of classical toxicity mechanisms. To overcome these issues, this research program aims to exploit the intrinsic toxicity of certain types of metal-based, degradation-prone NMs (Fe-doped ZnO, Fe-doped CuO and Ag of different sizes and coatings) towards only cancer cells as a novel and generic anti-cancer tool with 1) improved efficacy against difficult to treat cancers such as multidrug-resistant cancer cells, 2) enhanced specificity and selectivity of the treatment by the intrinsic cancer cell-specific toxicity of NMs towards cancer cells. To overcome the issues related to selective delivery of the NMs, tumor-homing cells will be used that have been shown to efficiently home to primary tumors and their metastases. In practice, the NMs used show distinct degradation kinetics that primarily induce cancer-selective toxicity. To obtain efficient tumor targeting, suicide gene-expressing tumor-homing cells will be loaded with the NMs in their cytoplasm, hereby impeding premature NM degradation. The tumor homing efficacy of these cells will be monitored via optical imaging and once at the target site these cells will be chemically destroyed using the suicide gene strategy. This will release the NMs into the tumor site, where they can selectively destroy the cancer cells. This research program will be the first to explore the full potential of cancer-specific toxicity of NMs and the use of cytoplasmic loading of cells as biological carriers for efficient delivery.

1 947 519 €

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

When an extended quantum system is suddenly brought out of thermodynamic equilibrium all excitations collectively participate in the ensuing quench dynamics, causing a plethora of unconventional and exotic effects, in particular in low spatial dimensions where the effects of interactions and integrability are enhanced. The theoretical study of the non-equilibrium dynamics is hampered by the fact that the time dependent many-body wave function is highly entangled on spatial scales which rapidly grow in time. Consequently, a satisfactory description of the quench dynamics is a timely challenge whose solution cannot prescind from a precise characterisation of the entanglement content of the systems of interest. The ambitious goal of this proposal is to find and characterise new non-equilibrium states of matter guided by their entanglement content. Two parallel lines of research will help achieving this goal. One line concerns the study of some entanglement indicators like entanglement Hamiltonian, spectrum, negativity and relative entropies which, contrary to the entanglement entropy, are not yet widely used as tools for investigating many-body systems. The other line focuses on the study of some frontiers of non-equilibrium one-dimensional physics which include quantum quenches in spinful fermionic systems, the determination of the exact time dependence of correlation functions after a quench, and the use of integrable hydrodynamics for investigating transport in one-dimensional systems. Particular attention will be devoted to the experimental realisation of the proposed non-equilibrium protocols. The main tools to achieve these goals will be conformal field theories and integrability complemented by numerical simulations when the former two are not applicable.

1 521 423 €

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

The Neolithic Transition in the Near East (c.10,000-6,000 BC) was a period of singular sociocultural change, when societies adopted sedentary life and agriculture for the first time in human history. This project will jointly use genomic and quantitative cultural data to explore Transition societies’ organisation, interactions, and their social and demographic evolution in time. (1) We will start by dissecting social structures within Neolithic communities in Anatolia, studying the role of kinship, postmarital residence customs, and endogamy. For this end, we will produce genotype data for c.250 individuals interred within five Pre-Pottery and Pottery Neolithic villages in South East and Central Anatolia, and analyse genomic relatedness patterns in the context of bioarchaeological similarity (e.g. by measuring genetic relatedness among Çatalhöyük individuals buried within the same house over generations). (2) We will study the means of cultural interaction among Near Eastern Neolithic societies by documenting which cultural traits -from skull removal customs to pottery- were most likely propagated through emulation and acculturation, and which ones by gene flow, when and where. Here we will produce whole genome data, compile genomic and material culture similarity matrices for >30 Near Eastern pre-Neolithic and Neolithic populations, and develop frameworks for integrated analysis of quantitative material culture and genomic similarity among populations (also including obsidian and sheep exchange connections as factors). The data will be analysed on multiple levels: within regions, interregional, and diachronic. (3) The work will conclude by examining the evolution of social organisation and population interaction patterns through the Neolithic Transition. While enriching and revising current Transition models, the project will set precedents for employing archaeogenomics to study social structures and for systematic co-analysis of genomic and archaeological data.

2 556 250 €

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

Comprehensive seismic programs undertaken in the past few years, combined with emerging new numerical technologies now provide the potential, for the first time, to explore in detail the Earth’s interior. However, such an integrated approach is currently not contemplated, which produces physical inconsistencies among the different studies that strongly bias our understanding of the Earth’s internal structure and dynamics. Of particular concern are nowadays apparent thermo-petrological anomalies in tomographic images that are generated by the unaccounted-for anisotropic structure of the mantle and that are commonly confused with real thermo-petrological features. Given the diffuse mantle seismic anisotropy, apparent thermo-petrological anomalies contaminate most tomographic models against which tectono-magmatic models are validated, representing a critical issue for the present-day window. Here we aim to develop a new methodology that combines state-of-the-art geodynamic modelling and seismological methods. The new methodology will allow building robust anisotropic tomographic models that will exploit anisotropy predictions from petrological-thermomechanical modelling to decompose velocity anomalies into isotropic (true thermo-petrological) and anisotropic (mechanically-induced) components. As a major outcome, we expect to provide a new, geodynamically and seismologically constrained perspective of the current deep structure and tectono-magmatic evolution of different tectonic settings. This new methodology will be applied to the Mediterranean and the Cascadia subduction zone where, despite the abundant seismological observations, large uncertainties about the subsurface structure and tectono-magmatic evolution persist. Furthermore, we plan to develop a new inversion technique for seismic anisotropy, and release an open source, sophisticated code for mantle fabric modelling, which will allow coupling geodynamic and seismological modelling in other tectonic settings.

1 466 030 €

Start date: 2018-03-01, End date: 2023-02-28

The use of graphic symbols in documentary records from the 4th to the 10th c. has so far received scant attention. ‘Graphic symbols’ are graphic signs (including alphabetical ones) drawn as a visual unit in a written text and representing something other than a word. They therefore broadly cover the semantic spectrum of the Latin ‘notae’ (signs) as opposed to ‘litterae’ (letters of the alphabet). With the gradual introduction of signature and the increasing use of papyrus from the 4th. c., the presence of graphic symbols became widespread in legal documents as it already was in other written records, and continued in post-Roman kingdoms as part of the same historical process of reception of the late antique documentary practice. Drawing symbols had a major social impact, because, provided it was done in one’s own hand, it placed on the same footing professional scribes, basic literates and illiterates. For illiterates, it certainly meant, both in the late Roman state (a Greek-Latin graphic and linguistic community) and in the post-Roman kindgdoms (as long as Latin functioned as language of vertical communication) a way of taking an active part in the writing process. A thorough investigation of this ‘other side’ of the written world can therefore provide precious insights about the spread of literacy as a whole. The available instances of graphic symbols, which number in their thousands, will be investigated in their contemporary context as well as diachronically, bringing together methods developed in the fields of palaeography, diplomatics and history. Archaeology, sociolinguistics, social anthropology and history of christianity will also provide important methodological angles. The census, description and images of these graphic symbols will be made available on the web through the relational and dynamic NOTAE-Database, which will be the main result of the project and, at the same time, the research tool for both the team members and all the interested scholars.

1 479 625 €

Start date: 2018-07-01, End date: 2023-06-30

This proposal originates from recent results obtained in the course of the Advanced ERC Project “OMVac”, the scope of which is to exploit the unique adjuvanticity properties of bacterial Outer Membrane Vesicles (OMVs) for developing innovative vaccines against infectious diseases and cancer. In particular, Synthetic Biology was applied to engineer OMVs with FAT1, a tumour associated antigen expressed in most primary and metastatic colorectal cancers (CRC). Using cancer models in immunocompetent mice, immunization with FAT1-decorated OMVs inhibited subcutaneous growth of FAT1-positive CT26 cancer cells and protection correlated with an increase in tumour infiltration of CD4+/CD8+ T cells and concomitant decrease of Treg and MDSCs. These promising results prompted the submission of the present proposal which has as main objectives: 1) the demonstration that FAT1-OMV immunization can synergise with the protective activity of checkpoint inhibitors, and 2) the development of a scalable FAT1-OMV production and purification process which could allow testing FAT1-OMV/checkpoint inhibitor combination in the clinical setting.

150 000 €

Start date: 2018-01-01, End date: 2019-06-30

This research explores the impact of property regimes on experiences of citizenship across five democratic countries: Greece, The Netherlands, Spain, the United Kingdom and the United States. Property rights are a foundational element of democracy, but the right to private property exists in tension with values of equality and a right to shelter. An investigation of property is urgent given the recent normalisation of economic models that have resulted in millions of evictions every year. Through an ethnographic study of eviction this research provides a comparative analysis of the benefits and limitations of contemporary property regimes for democratic citizenship. A property regime is defined as the combination of moral discourses about real landed property with the regulatory policies and market mechanisms that shape the use, sale and purchase of property. The selected countries represent a diverse set of property regimes, but all five are experiencing a housing and eviction crisis that has created new geographies of disadvantage, exacerbated inequalities of race, gender, age and income, and led to social unrest. Building on the PI's previous research into citizen-driven democratic innovation, this research critically examines the concept of property through a novel methodology dubbed 'conflictive context construction' that employs a qualitative approach centred on moments of conflict resulting from the use, sale or purchase of specific properties to answer: how do property regimes shape people's experience of citizenship and what can this tell us about the role of property in contemporary models of democratic governance? The high gain of this research lies in the opportunity to rethink the role of property within democracy based on extensive empirical data about how moral assumptions combine with particular ways of regulating and marketing property to exacerbate, alleviate or create inequalities within contemporary experiences of democratic citizenship.

1 970 688 €

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

The project creates a new Digital Grammar of Greek Documentary Papyri. It fills a void in Greek scholarship: the papyrological corpus represents the Post-Classical variety of Greek, a bridge between Classical and Medieval Greek, which has hitherto been very difficult to use as a source for studying historical linguistics. This project will develop new digital methods for studying this fragmentary but vast text corpus. Greek is a unique language for linguists in its chronological scope. Documentary Greek papyri, ranging from ca. 300 BCE to 700 CE, can be contrasted with literature: these papyri preserve us the language as the ancient writer composed it and lead us close to the colloquial contemporary language. The nonstandard variation in documentary texts is where language change can first be detected, making the papyrological corpus an important source for diachronic study of Greek. The new Grammar of Greek papyri will answer such questions as how much bilingualism affected Greek in Egypt and when and where it was a dominant feature of the society. The papyri will partly be treated as big data; the whole corpus will be morphologically tagged. This will enable e.g. phonological analyses to be performed in greater accuracy than has been possible before through eliminating the confusion between inflectional morphology and phonological variation. As a result, the Digital Grammar will bring the language used in the Greek papyri openly available to the scholarly community in an unforeseen manner. It will include new, more exact analyses of the phonology and morphology of Greek in Egypt, as well as a possibility to search both phonological and morphological forms, in combination or in separation, in the whole corpus. The syntactically annotated corpora will form a smaller but constantly expanding corpus of selected papyri, which yields to a wider range of searches on morphosyntax.

1 495 584 €

Start date: 2018-03-01, End date: 2023-02-28