ERC FUNDED PROJECTS

Hepatitis B virus (HBV) infections remain a major public health issue worldwide. Over 350 -400 million people are chronically infected by HBV, and about 1 million people die each year from the complications of this infection (cirrhosis and hepatocellular carcinoma) with a consequent hefty economic impact on national health systems. This led the World Health Organization to recognise HBV infection as a key priority and adopt the global health sector strategy to eliminate viral hepatitis, with a target of reducing new infections by 90% and mortality by 65% by 2030. The risk of developing a chronic infection in healthy adults is due to a weaker, dysfunctional and narrowly focused CD8+ T cell response. Since the mechanisms underlying HBV persistence are not fully elucidated, current treatments (antiviral drugs and Interferon) aim to reduce the development of liver disease, while a definitive treatment for curing this infection is not yet available on the market. Within the ERC Consolidator Grant 725038 “FATE”, we recently characterized the mechanisms behind the ineffective CD8+ T cell response towards HBV, demonstrating the potential efficacy of interleukin-2 (IL-2) – a cytokine – to reactivate it, thus achieving antiviral activity. This discovery, jointly with our proprietary third-generation, self-inactivating lentiviral vectors (LVs) that allow selective hepatocellular expression of IL-2, pave the way to single-dose gene therapy-based approach, a potential functional cure against chronic hepatitis B. 2LIVEr project intends to optimize and further validate our novel therapeutic approach from both a technical and commercial standpoint, moving from TRL3 to TRL4, thus fastening the roadmap towards the market.

150 000 €

Start date: 2020-07-01, End date: 2021-12-31

Photonics, in recognition of its strategic significance and pervasiveness throughout many industrial sectors, has been identified as one of the Key Enabling Technologies for Europe. Photonics in combination with quantum information science has great potential to facilitate, transform and innovate future technologies for the better. The Proof of Concept (PoC) project intends to contribute to this by developing and testing a communication platform prototype, comprised of single photon detectors, which are efficiently coupled to single mode fibers using an innovative laser written device. This enables the integration of single photon detectors on innovative glass waveguides. These glass integrated photonic circuits offer excellent specifics for on-chip quantum optics implementations in terms of scattering losses, offering flexibility of the waveguide geometry and ensuring high coupling efficiency with optical fibers. The device developed and tested in the PoC, directly addresses a market need for an integrated and efficient on-chip communication systems. Current available systems have limitations involving high costs, complex production, and inefficient coupling of detectors to optical fibers. The proposed platform will offer 1.) a simplified production process, 2.) high optical fiber coupling efficiency 3.) improved performance levels, 4.) high cost efficiency, and 5.) compactness. Such systems can be applied in a wide range of communication and non-communication applications, such as free-space optical communication, quantum communication, quantum cryptography, DNA sequencing, single molecule detection and material analysis. Moreover, the future commercialisation of quantum computing is expected to create a vast demand for these communication systems. In addition to the technology PoC, the project carries out IPR strategy considerations through patenting actions, determines the market potential, seeks market feedback, and plans for post-PoC commercialisation paths.

150 000 €

Start date: 2016-02-01, End date: 2017-07-31

How does the inside of the proton look like? What generates its spin?
3DSPIN will deliver essential information to answer these questions at the frontier of subnuclear physics. At present, we have detailed maps of the distribution of quarks and gluons in the nucleon in 1D (as a function of their momentum in a single direction). We also know that quark spins account for only about 1/3 of the spin of the nucleon. 3DSPIN will lead the way into a new stage of nucleon mapping, explore the distribution of quarks in full 3D momentum space and obtain unprecedented information on orbital angular momentum. Goals 1. extract from experimental data the 3D distribution of quarks (in momentum space), as described by Transverse-Momentum Distributions (TMDs); 2. obtain from TMDs information on quark Orbital Angular Momentum (OAM). Methodology 3DSPIN will implement state-of-the-art fitting procedures to analyze relevant experimental data and extract quark TMDs, similarly to global fits of standard parton distribution functions. Information about quark angular momentum will be obtained through assumptions based on theoretical considerations. The next five years represent an ideal time window to accomplish our goals, thanks to the wealth of expected data from deep-inelastic scattering experiments (COMPASS, Jefferson Lab), hadronic colliders (Fermilab, BNL, LHC), and electron-positron colliders (BELLE, BABAR). The PI has a strong reputation in this field. The group will operate in partnership with the Italian National Institute of Nuclear Physics and in close interaction with leading experts and experimental collaborations worldwide. Impact Mapping the 3D structure of chemical compounds has revolutionized chemistry. Similarly, mapping the 3D structure of the nucleon will have a deep impact on our understanding of the fundamental constituents of matter. We will open new perspectives on the dynamics of quarks and gluons and sharpen our view of high-energy processes involving nucleons.

1 509 000 €

Start date: 2015-07-01, End date: 2020-12-31

Goal of the 4DPHOTON project is the development and construction of a photon imaging detector with unprecedented performance. The proposed device will be capable of detecting fluxes of single-photons up to one billion photons per second, over areas of several square centimetres, and will measure - for each photon - position and time simultaneously with resolutions better than ten microns and few tens of picoseconds, respectively. These figures of merit will open many important applications allowing significant advances in particle physics, life sciences or other emerging fields where excellent timing and position resolutions are simultaneously required. Our goal will be achieved thanks to the use of an application-specific integrated circuit in 65 nm complementary metal-oxide-semiconductor (CMOS) technology, that will deliver a timing resolution of few tens of picoseconds at the pixel level, over few hundred thousand individually-active pixel channels, allowing very high rates of photons to be detected, and the corresponding information digitized and transferred to a processing unit. As a result of the 4DPHOTON project we will remove the constraints that many light imaging applications have due to the lack of precise single-photon information on four dimensions (4D): the three spatial coordinates and time simultaneously. In particular, we will prove the performance of this detector in the field of particle physics, performing the reconstruction of Cherenkov photon rings with a timing resolution of ten picoseconds. With its excellent granularity, timing resolution, rate capability and compactness, this detector will represent a new paradigm for the realisation of future Ring Imaging Cherenkov detectors, capable of achieving high efficiency particle identification in environments with very high particle multiplicities, exploiting time-association of the photon hits.

1 975 000 €

Start date: 2019-12-01, End date: 2024-11-30

The problem: Cancer metastases are responsible for 90% of cancer-associated deaths. Circulating tumour cells (CTCs) that enter the blood stream on their way to potential metastatic sites are of obvious interest to evaluate correctly patient treatment and therefore influence outcome. CTCs have been identified in bladder, gastric, prostate, lung, breast and colon cancer. The only FDA approved CTCs detection system is Veridex’ CellSearch, which detects only epithelial cancer cells using antibody labelling. Recent evidence showed that non-epithelial cancer cells, which are not detected by CellSearch, are of critical importance in cancer progression. The idea: Our CTC detection method is based, instead of on antibody labelling, on metabolic features of cancer cells, thus providing potential for detecting both epithelial and mesenchymal cancer cells. Cancer cells induce environmental changes; e.g. in aerobic conditions most cancer cells display a high rate of glycolysis with lactate production in the cytosol, known as the Warburg effect. By separating cells into micro-droplets of pico-liter volume using micro-fluidic water-in-oil emulsions and by characterising the microenvironment surrounding them, CTCs are detected by probing for environmental changes using pH sensitive dyes or enzymatic lactate assays. Our inexpensive diagnostic method provides a way to count and isolate CTCs without any labelling while maintaining cells alive and intact for further studies. The project: “A CACTUS” is meant to assess the feasibility of commercialising the developed method for counting and sorting CTCs and develop a proper commercialisation strategy. The final goal of this project is to develop a proposition package consisting of technical proof of concept, the business proposition and strategy and an IP portfolio and strategy. This information will be presented in an attractive business plan that will be proposed to potential investors.

149 875 €

Start date: 2015-04-01, End date: 2016-09-30

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

This project aims at creating a multimedia archive of the printed works of Anton Francesco Doni, who was not only an author but also a typographer, a publisher and a member of the Giolito and Marcolini’s editorial staff. The analysis of Doni’s work may be a good way to investigate appropriation, text rewriting and image reusing practices which are typical of several authors of the 16th Century, as clearly shown by the critics in the last decades. This project intends to bring to light the wide range of impulses from which Doni’s texts are generated, with a great emphasis on the figurative aspect. The encoding of these texts will be carried out using the TEI (Text Encoding Initiative) guidelines, which will enable any single text to interact with a range of intertextual references both at a local level (inside the same text) and at a macrostructural level (references to other texts by Doni or to other authors). The elements that will emerge from the textual encoding concern: A) The use of images Real images: the complex relation between Doni’s writing and the xylographies available in Marcolini’s printing-house or belonging to other collections. Mental images: the remarkable presence of verbal images, as descriptions, ekphràseis, figurative visions, dreams and iconographic allusions not accompanied by illustrations, but related to a recognizable visual repertoire or to real images that will be reproduced. B) The use of sources A parallel archive of the texts most used by Doni will be created. Digital anastatic reproductions of the 16th-Century editions known by Doni will be provided whenever available. The various forms of intertextuality will be divided into the following typologies: allusions; citations; rewritings; plagiarisms; self-quotations. Finally, the different forms of narrative (tales, short stories, anecdotes, lyrics) and the different idiomatic expressions (proverbial forms and wellerisms) will also be encoded.

559 200 €

Start date: 2008-08-01, End date: 2012-07-31

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

Interferometers are fundamental tools for the study of nature laws and for the precise measurement and control of the physical world. In the last century, the scientific and technological progress has proceeded in parallel with a constant improvement of interferometric performances. For this reason, the challenge of conceiving and realizing new generations of interferometers with broader ranges of operation and with higher sensitivities is always open and actual. Despite the introduction of laser devices has deeply improved the way of developing and performing interferometric measurements with light, the atomic matter wave analogous, i.e. the Bose-Einstein condensate (BEC), has not yet triggered any revolution in precision interferometry. However, thanks to recent improvements on the control of the quantum properties of ultra-cold atomic gases, and new original ideas on the creation and manipulation of quantum entangled particles, the field of atom interferometry is now mature to experience a big step forward. The system I want to realize is a Mach-Zehnder spatial interferometer operating with trapped BECs. Undesired decoherence sources will be suppressed by implementing BECs with tunable interactions in ultra-stable optical potentials. Entangled states will be used to improve the sensitivity of the sensor beyond the standard quantum limit to ideally reach the ultimate, Heisenberg, limit set by quantum mechanics. The resulting apparatus will show unprecedented spatial resolution and will overcome state-of-the-art interferometers with cold (non condensed) atomic gases. A successful completion of this project will lead to a new generation of interferometers for the immediate application to local inertial measurements with unprecedented resolution. In addition, we expect to develop experimental capabilities which might find application well beyond quantum interferometry and crucially contribute to the broader emerging field of quantum-enhanced technologies.

1 068 000 €

Start date: 2011-01-01, End date: 2015-12-31

ALK positive cancer such as Anaplastic Large Cell Lymphoma (ALCL), Non small Cell Lung Carcinoma (NSCLC) and neuroblastoma are important cancers of children and adults, currently treated with standard chemotherapy and radiotherapy, with unpredicatable and poor results, in particular in the case of NSCLC and neuroblastoma. In August 2011, the US Food and Drug Administration (FDA) had an accelerated approval of a novel drug (called Crizotinib) to treat NSCLC that express abnormal ALK protein. Phase II and III clinical trials are ongoing to test the same drug in ALCL and neuroblastoma. However, it is now clear that the treatment with Crizotinib has a good initial efficacy and response, but the cancer inevitably relapses because of the occurrence of drug resistance. This resistance is due to selection of ALK point mutants that no longer bind the inhibitor. New drugs to tame the resistant cells will be probably developed in the future (as happened for Gleevec and second and third generation of BCR-ABL inhibitors), but it is expected that again resistance will emerge. As part of a research conducted under an ERC Starting Grat, we developed a new therapy for ALK positive ALCL, NSCLC and neuroblastoma based on the generation of a potent and specific anti-tumor response based on the development of an ALK-targeted immune response. This specific anti-ALK immune response is achieved by an anti-ALK vaccination in preclinical mouse models of ALCL and NSCLC. Now, in this Proof-of-Concept grant, we propose to take the next steps to move our invention toward a clinical application in human patients, by testing GLP formulations of the vaccine, its potential toxic effects and by searching the market for companies interested in its development and commercialization. Our goal is to understand and finalize the best strategy to move this experimental therapy to the market and generate a partnership with a pharma company.

149 939 €

Start date: 2013-06-01, End date: 2014-05-31

ALPI aims at the integration of a photonic neural network within an optical transceiver to increase the transmission capacity of the optical link. Based on a deep learning approach, the new compact device provides real time compensation of fiber nonlinearities which degrade optical signals. In fact, the tremendous growth of transmission bandwidth both in optical networks as well as in data centers is baffled by the optical fiber nonlinear Shannon capacity limit. Nowadays, computational intensive approaches based on power hungry software are commonly used to mitigate fiber nonlinearities. Here, we propose to integrate in the optical link the neuromorphic photonic circuits which we are currently developing in the ERC-AdG BACKUP project. Specifically, the proposed error-correction circuit implements a small all-optical complex-valued neural network which is able to recover distortion on the optical transmitted data caused by the Kerr nonlinearities in multiwavelength optical fibers. Network training is realized by means of efficient gradient-free methods using a properly designed data-preamble. A new neuromorphic transceiver demonstrator realized in active hybrid Si/InP technology will be designed, developed and tested on a 100 Gbps 80 km long optical link with multiple-levels symbols. The integrated neural network will mitigate the nonlinearities either by precompensation/autoencoding at the transmitter TX side or by data correction at the receiver RX side or by concurrently acting on both the TX and RX sides. This achievement will bear to the second ALPI’s goal: moving from the demonstrator to the industrialization of the improved transceiver. For this purposes, patents will be filed and a business plan will be developed in partnership with semiconductor, telecom and IT companies where a path to the commercialization will be individuated. The foreseen market is the big volume market of optical interconnection in large data centers or metro networks.

150 000 €

Start date: 2020-11-01, End date: 2022-04-30

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

2 328 736 €

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

Normal placental angiogenesis is critical for embryonic survival and development. Epigenetic modifications, such as methylation of CpG islands, regulate the expression and imprinting of genes. Epigenetic abnormalities have been observed in embryos from assisted reproductive technologies (ART), which could explain the poor placental vascularisation, embryonic/fetal death, and altered fetal growth in these pregnancies. Both cloned (somatic cell nuclear transfer, or SNCT) and monoparental (parthogenotes, only maternal genes; androgenotes, only paternal genes) embryos provide important models for studying defects in expression and methylation status/imprinting of genes regulating placental function. Our hypothesis is that placental vascular development is compromised during early pregnancy in embryos from ART, in part due to altered expression or imprinting/methylation status of specific genes regulating placental angiogenesis. We will evaluate fetal growth, placental vascular growth, and expression and epigenetic status of genes regulating placental angiogenesis during early pregnancy in 3 Specific Aims: (1) after natural mating; (2) after transfer of biparental embryos from in vitro fertilization, and SCNT; and (3) after transfer of parthenogenetic or androgenetic embryos. These studies will therefore contribute substantially to our understanding of the regulation of placental development and vascularisation during early pregnancy, and could pinpoint the mechanism contributing to embryonic loss and developmental abnormalities in foetuses from ART. Any or all of these observations will contribute to our understanding of and also our ability to successfully employ ART, which are becoming very wide spread and important in human medicine as well as in animal production.

363 600 €

Start date: 2008-10-01, End date: 2012-06-30

Isoperimetric and Sobolev inequalities are the best known examples of geometric-functional inequalities. In recent years the PI and collaborators have obtained new and sharp quantitative versions of these and other important related inequalities. These results have been obtained by the combined use of classical symmetrization methods, new tools coming from mass transportation theory, deep geometric measure tools and ad hoc symmetrizations. The objective of this project is to further develop thes techniques in order to get: sharp quantitative versions of Faber-Krahn inequality, Gaussian isoperimetric inequality, Brunn-Minkowski inequality, Poincaré and Sobolev logarithm inequalities; sharp decay rates for the quantitative Sobolev inequalities and Polya-Szegö inequality.

600 000 €

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

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

1 483 180 €

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

The aim of AROMA-CFD is to create a team of scientists at SISSA for the development of Advanced Reduced Order Modelling techniques with a focus in Computational Fluid Dynamics (CFD), in order to face and overcome many current limitations of the state of the art and improve the capabilities of reduced order methodologies for more demanding applications in industrial, medical and applied sciences contexts. AROMA-CFD deals with strong methodological developments in numerical analysis, with a special emphasis on mathematical modelling and extensive exploitation of computational science and engineering. Several tasks have been identified to tackle important problems and open questions in reduced order modelling: study of bifurcations and instabilities in flows, increasing Reynolds number and guaranteeing stability, moving towards turbulent flows, considering complex geometrical parametrizations of shapes as computational domains into extended networks. A reduced computational and geometrical framework will be developed for nonlinear inverse problems, focusing on optimal flow control, shape optimization and uncertainty quantification. Further, all the advanced developments in reduced order modelling for CFD will be delivered for applications in multiphysics, such as fluid-structure interaction problems and general coupled phenomena involving inviscid, viscous and thermal flows, solids and porous media. The advanced developed framework within AROMA-CFD will provide attractive capabilities for several industrial and medical applications (e.g. aeronautical, mechanical, naval, off-shore, wind, sport, biomedical engineering, and cardiovascular surgery as well), combining high performance computing (in dedicated supercomputing centers) and advanced reduced order modelling (in common devices) to guarantee real time computing and visualization. A new open source software library for AROMA-CFD will be created: ITHACA, In real Time Highly Advanced Computational Applications.

1 656 579 €

Start date: 2016-05-01, End date: 2021-10-31

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

2 193 375 €

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

Verifying the correctness of software systems requires extensive and expensive testing sessions. While there are tools and methodologies to efficiently address unit and integration testing, system testing is still largely the result of manual effort. Testing software applications at the system level requires executing the applications through their interfaces to verify the correctness of their functionalities and stimulate all their layers and components. Automating just part of this process can dramatically improve the effectiveness of verification activities and significantly reduce development costs, relevantly alleviating developers from their verification effort. This project addresses the development of a pre-commercial tool that has the unique capability of efficiently and automatically generating semantically-relevant system test cases equipped with functional oracles. This capability derives from the AUGUSTO technique, which is an outcome of the Learn ERC project. The idea behind Augusto is to exploit the common-sense knowledge, that is, the background knowledge that every computer user has and that normally lets her/him use software applications without the need of accessing any documentation or manual. Once this knowledge is represented abstractly and then embedded in AUGUSTO, the technique can automatically adapt its definition to the software under test every time a program is tested. This development work will be performed jointly with A company that produces and markets testing tools.

150 000 €

Start date: 2019-01-01, End date: 2020-06-30

Astaxanthin is a carotenoid with a high commercial value. Its high anti-oxidant activity makes Astaxanthin being used as a food/feed supplements, in cosmetics, and in nutraceutics. Microalgae are the main primary sources of Astaxanthin, being produced at industrial level mainly by cultivation of the green alga Haematococcus pluvialis with high costs for cultivation and extraction, hindering its market. In the ERC-StG-SOLENALGAE project the investigation of the role of carotenoids in photoprotection in microalgae led to the development of an innovative platform for Astaxanthin production. Strains with high Astaxanthin accumulation were indeed obtained by metabolic engineering in the green alga Chlamydomonas reinhardtii (usually not accumulating Astaxanthin), producing up to 4 mg/L per day in non-optimized growth conditions. Astaxanthin production by bkt15 strain revealed unique advantages compared to other source of natural Astaxanthin: production of Astaxanthin in continuous, in a single cultivation step; high bio-accessibility for animal or human assimilation; easier extraction of astaxanthin even without costly cell pre-treatments; lower extraction costs and no contamination from oxidant molecules as chlorophylls during extraction process. These advantages lead to a potential increase in pure Astaxanthin productivity up to 16-fold higher than the current methods. ASTEASY PoC aims to the technological development of the new system, by optimizing the cultivation conditions and extraction processes of Astaxanthin from the bkt15 strain and validating the performances in 60 litres demonstrator units. We will also identify and protect the IP generated and analyse the certification needed for commercialization. A business plan will be drafted as a result of interactions with stakeholders and literature analysis, to define market size and trends, and consolidate the business model (Astaxanthin production through a dedicated spin-off vs licensing to Astaxanthin producers).

150 000 €

Start date: 2020-03-01, End date: 2021-08-31

Recent works indicate the pathogenic relevance of altered RNA metabolism and aberrant ribonucleoprotein (RNP) assembly in several neurodegenerative diseases, such as Amyotrophic lateral sclerosis. How defective RNPs form, what are their integral components and which events trigger their appearance late in life are still unsolved issues. While emerging evidence indicates that mutations and post-translational modifications of specific RNA-binding proteins (RBPs) induce liquid-solid phase transition in vitro, much less is known about the in vivo properties of RNP assemblies and which role RNA plays in their formation. ASTRA will combine sophisticated imaging-derived RNP complex purification with innovative computational approaches and powerful genetic tools to unravel the biophysical properties and composition of RBP complexes and how they are modified in disease conditions. Through the development of new imaging and optical methods we plan to study how RNPs separate in liquid and solid phases in cells, in tissues (retina) and animal models and to characterize their RNA and protein components in physiological and pathological states. Exploiting the novel finding that non-coding RNAs act as scaffolding molecules for RNP assembly, we will investigate how such RNAs control the dynamic link between RNP formation, intracellular sorting and function. In a genuine interdisciplinary team effort, we will reveal how the architecture and localization of cytoplasmic RNP complexes are controlled in motor neurons and affected in neurodegeneration. We plan to develop novel advanced microscopy methods to monitor formation of aberrant RNPs in vivo and we will explore new molecules to impede pathological cascades driven by RNP assemblies. In conclusion, ASTRA will allow us to gain a comprehensive understanding of RNP function and dysfunction; we will use this knowledge to develop new therapeutic strategies that will impact on several protein-misfolding neurodegenerative diseases.

7 741 799 €

Start date: 2020-03-01, End date: 2026-02-28

Autism spectrum disorders (ASD) affect 1-2% of the population and are a major public health issue. Heterogeneity between affected ASD individuals is substantial both at clinical and etiological levels, thus warranting the idea that we should begin characterizing the ASD population as multiple kinds of ‘autisms’. Without an advanced understanding of how heterogeneity manifests in ASD, it is likely that we will not make pronounced progress towards translational research goals that can have real impact on patient’s lives. This research program is focused on decomposing heterogeneity in ASD at multiple levels of analysis. Using multiple ‘big data’ resources that are both ‘broad’ (large sample size) and ‘deep’ (multiple levels of analysis measured within each individual), I will examine how known variables such as sex, early language development, early social preferences, and early intervention treatment response may be important stratification variables that differentiate ASD subgroups at phenotypic, neural systems/circuits, and genomic levels of analysis. In addition to examining known stratification variables, this research program will engage in data-driven discovery via application of advanced unsupervised computational techniques that can highlight novel multivariate distinctions in the data that signal important ASD subgroups. These data-driven approaches may hold promise for discovering novel ASD subgroups at biological and phenotypic levels of analysis that may be valuable for prioritization in future work developing personalized assessment, monitoring, and treatment strategies for subsets of the ASD population. By enhancing the precision of our understanding about multiple subtypes of ASD this work will help accelerate progress towards the ideals of personalized medicine and help to reduce the burden of ASD on individuals, families, and society.

1 499 444 €

Start date: 2018-01-01, End date: 2023-12-31

Massive black hole binaries (MBHBs) are the most extreme, fascinating yet elusive astrophysical objects in the Universe. Establishing observationally their existence will be a milestone for contemporary astronomy, providing a fundamental missing piece in the puzzle of galaxy formation, piercing through the (hydro)dynamical physical processes shaping dense galactic nuclei from parsec scales down to the event horizon, and probing gravity in extreme conditions. We can both see and listen to MBHBs. Remarkably, besides arguably being among the brightest variable objects shining in the Cosmos, MBHBs are also the loudest gravitational wave (GW) sources in the Universe. As such, we shall take advantage of both the type of messengers – photons and gravitons – they are sending to us, which can now be probed by all-sky time-domain surveys and radio pulsar timing arrays (PTAs) respectively. B MASSIVE leverages on a unique comprehensive approach combining theoretical astrophysics, radio and gravitational-wave astronomy and time-domain surveys, with state of the art data analysis techniques to: i) observationally prove the existence of MBHBs, ii) understand and constrain their astrophysics and dynamics, iii) enable and bring closer in time the direct detection of GWs with PTA. As European PTA (EPTA) executive committee member and former I International PTA (IPTA) chair, I am a driving force in the development of pulsar timing science world-wide, and the project will build on the profound knowledge, broad vision and wide collaboration network that established me as a world leader in the field of MBHB and GW astrophysics. B MASSIVE is extremely timely; a pulsar timing data set of unprecedented quality is being assembled by EPTA/IPTA, and Time-Domain astronomy surveys are at their dawn. In the long term, B MASSIVE will be a fundamental milestone establishing European leadership in the cutting-edge field of MBHB astrophysics in the era of LSST, SKA and LISA.

1 532 750 €

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

This project intends to study intercultural connections in contemporary Europe, engaging both native and ‘new’ Europeans. These connections are woven through the faculties of embodied subjects – memory, visuality and mobility – and concern the movement of people, ideas and images across the borders of European nation-states. These faculties are connected with that of affect, an increasingly important concept in history and the social sciences. Memory will be understood not only as oral or direct memory, but also as cultural memory, embodied in various cultural products. Our study aims to understand new forms of European identity, as these develop in an increasingly diasporic world. Europe today is not only a key site of immigration, after having been for centuries an area of emigration, but also a crucial point of arrival in a global network designed by mobile human beings. Three parts will make up the project. The first will engage with bodies, their gendered dimension, performative capacities and connection to place. It will explore the ways certain bodies are ‘emplaced’ as ‘European’, while others are marked as alien, and contrast these discourses with the counter-narratives by visual artists. The second part will extend further the reflection on the role of the visual arts in challenging an emergent ‘Fortress Europe’ but also in re-imagining the memory of European colonialism. The work of some key artists will be shown to students in Italy and the Netherlands, both recent migrants and ‘natives’, creating an ‘induced reception’. The final part of the project will look at alternative imaginations of Europe, investigating the oral memories and ‘mental maps’ created by two migrant communities in Europe: from Peru and from the Horn of Africa. Examining the heterogeneous micro-productions of mobility – whether ‘real’ or imagined/envisioned – will thus yield important lessons for the historical understanding of inclusion and exclusion in today’s Europe.

1 488 501 €

Start date: 2013-06-01, End date: 2018-05-31

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

Monoclonal antibodies against the EGF receptor (EGFR) provide substantive benefit to colorectal cancer (CRC) patients. However, no genetic lesions that robustly predict ‘addiction’ to the EGFR pathway have been yet identified. Further, even in tumours that regress after EGFR blockade, subsets of drug-tolerant cells often linger and foster ‘minimal residual disease’ (MRD), which portends tumour relapse. Our preliminary evidence suggests that reliance on EGFR activity, as opposed to MRD persistence, could be assisted by genetically-based variations in transcription factor partnerships and activities, gene expression outputs, and biological fates controlled by the WNT/beta-catenin pathway. On such premises, BEAT (Beta-catenin and EGFR Abrogation Therapy) will elucidate the mechanisms of EGFR dependency, and escape from it, with the goal to identify biomarkers for more efficient clinical management of CRC and develop new therapies for MRD eradication. A multidisciplinary approach will be pursued spanning from integrative gene regulation analyses to functional genomics in vitro, pharmacological experiments in vivo, and clinical investigation, to address whether: (i) specific genetic alterations of the WNT pathway affect anti-EGFR sensitivity; (ii) combined neutralisation of EGFR and WNT signals fuels MRD deterioration; (iii) data from analysis of this synergy can lead to the discovery of clinically meaningful biomarkers with predictive and prognostic significance. This proposal capitalises on a unique proprietary platform for high-content studies based on a large biobank of viable CRC samples, which ensures strong analytical power and unprecedented biological flexibility. By providing fresh insight into the mechanisms whereby WNT/beta-catenin signalling differentially sustains EGFR dependency or drug tolerance, the project is expected to put forward an innovative reinterpretation of CRC molecular bases and advance the rational application of more effective therapies.

1 793 421 €

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

Cavitation is the formation of vapor cavities inside a liquid due to low pressure. Cavitation is an ubiquitous and destructive phenomenon common to most engineering applications that deal with flowing water. At the same time, the extreme conditions realized in cavitation are increasingly exploited in medicine, chemistry, and biology. What makes cavitation unpredictable is its multiscale nature: nucleation of vapor bubbles heavily depends on micro- and nanoscale details; mesoscale phenomena, as bubble collapse, determine relevant macroscopic effects, e.g., cavitation damage. In addition, macroscopic flow conditions, such as turbulence, have a major impact on it. The objective of the BIC project is to develop the lacking multiscale description of cavitation, by proposing new integrated numerical methods capable to perform quantitative predictions. The detailed and physically sound understanding of the multifaceted phenomena involved in cavitation (nucleation, bubble growth, transport, and collapse in turbulent flows) fostered by BIC project will result in new methods for designing fluid machinery, but also therapies in ultrasound medicine and chemical reactors. The BIC project builds upon the exceptionally broad experience of the PI and of his research group in numerical simulations of flows at different scales that include advanced atomistic simulations of nanoscale wetting phenomena, mesoscale models for multiphase flows, and particle-laden turbulent flows. The envisaged numerical methodologies (free-energy atomistic simulations, phase-field models, and Direct Numerical Simulation of bubble-laden flows) will be supported by targeted experimental activities, designed to validate models and characterize realistic conditions.

2 491 200 €

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

"Nanomaterials such as carbon nanotubes or graphene sheets represent the future of material science, due to their potentially exceptional mechanical properties. One great drawback of all artificial materials, however, is the decrease of strength with increasing toughness, and viceversa. This problem is not encountered in many biological nanomaterials (e.g. spider silk, bone, nacre). Other biological materials display exceptional adhesion or damping properties, and can be self-cleaning or self-healing. The “secret” of biomaterials seems to lie in “hierarchy”: several levels can often be identified (2 in nacre, up to 7 in bone and dentine), from nano- to micro-scale. The idea of this project is to combine Nature and Nanotechnology to design hierarchical composites with tailor made characteristics, optimized with respect to both strength and toughness, as well as materials with strong adhesion/easy detachment, smart damping, self-healing/-cleaning properties or controlled energy dissipation. For example, one possible objective is to design the “world’s toughest composite material”. The potential impact and importance of these goals on materials science, the high-tech industry and ultimately the quality of human life could be considerable. In order to tackle such a challenging design process, the PI proposes to adopt ultimate nanomechanics theoretical tools corroborated by continuum or atomistic simulations, multi-scale numerical parametric simulations and Finite Element optimization procedures, starting from characterization experiments on biological- or nano-materials, from the macroscale to the nanoscale. Results from theoretical, numerical and experimental work packages will be applied to a specific case study in an engineering field of particular interest to demonstrate importance and feasibility, e.g. an airplane wing with a considerably enhanced fatigue resistance and reduced ice-layer adhesion, leading to a 10 fold reduction in wasted fuel."

1 004 400 €

Start date: 2012-01-01, End date: 2016-12-31

The use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine. More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.

1 748 125 €

Start date: 2016-02-01, End date: 2022-07-31

The BioMNP objective is the molecular-level understanding of the interactions between surface functionalized metal nanoparticles and biological membranes, by means of cutting-edge computational techniques and new molecular models. Metal nanoparticles (NP) play more and more important roles in pharmaceutical and medical technology as diagnostic or therapeutic devices. Metal NPs can nowadays be engineered in a multitude of shapes, sizes and compositions, and they can be decorated with an almost infinite variety of functionalities. Despite such technological advances, there is still poor understanding of the molecular processes that drive the interactions of metal NPs with cells. Cell membranes are the first barrier encountered by NPs entering living organisms. The understanding and control of the interaction of nanoparticles with biological membranes is therefore of paramount importance to understand the molecular basis of the NP biological effects. BioMNP will go beyond the state of the art by rationalizing the complex interplay of NP size, composition, functionalization and aggregation state during the interaction with model biomembranes. Membranes, in turn, will be modelled at an increasing level of complexity in terms of lipid composition and phase. BioMNP will rely on cutting-edge simulation techniques and facilities, and develop new coarse-grained models grounded on finer-level atomistic simulations, to study the NP-membrane interactions on an extremely large range of length and time scales. BioMNP will benefit from important and complementary experimental collaborations, will propose interpretations of the available experimental data and make predictions to guide the design of functional, non-toxic metal nanoparticles for biomedical applications. BioMNP aims at answering fundamental questions at the crossroads of physics, biology and chemistry. Its results will have an impact on nanomedicine, toxicology, nanotechnology and material sciences.

1 131 250 €

Start date: 2016-04-01, End date: 2021-11-30

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

700 000 €

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

If you suddenly hear your song on the radio and spontaneously decide to burst into dance in your living room, you need to precisely time your movements if you do not want to find yourself on your bookshelf. Most of what we do or perceive depends on how accurately we represent the temporal properties of the environment however we cannot see or touch time. As such, time in the millisecond range is both a fundamental and elusive dimension of everyday experiences. Despite the obvious importance of time to information processing and to behavior in general, little is known yet about how the human brain process time. Existing approaches to the study of the neural mechanisms of time mainly focus on the identification of brain regions involved in temporal computations (‘where’ time is processed in the brain), whereas most computational models vary in their biological plausibility and do not always make clear testable predictions. BiT is a groundbreaking research program designed to challenge current models of time perception and to offer a new perspective in the study of the neural basis of time. The groundbreaking nature of BiT derives from the novelty of the questions asked (‘when’ and ‘how’ time is processed in the brain) and from addressing them using complementary but distinct research approaches (from human neuroimaging to brain stimulation techniques, from the investigation of the whole brain to the focus on specific brain regions). By testing a new biologically plausible hypothesis of temporal representation (via duration tuning and ‘chronotopy’) and by scrutinizing the functional properties and, for the first time, the temporal hierarchies of ‘putative’ time regions, BiT will offer a multifaceted knowledge of how the human brain represents time. This new knowledge will challenge our understanding of brain organization and function that typically lacks of a time angle and will impact our understanding of how the brain uses time information for perception and action

1 670 830 €

Start date: 2016-10-01, End date: 2022-09-30

Autophagy is a fundamental cellular catabolic process deputed to the degradation and recycling of a variety of intracellular materials. Autophagy plays a significant role in multiple human physio-pathological processes and is now emerging as a critical regulator of skeletal development and homeostasis. We have discovered that during postnatal development in mice, the growth factor FGF18 induces autophagy in the chondrocyte cells of the growth plate to regulate the secretion of type II collagen, a major component of cartilaginous extracellular matrix. The FGF signaling pathways play crucial roles during skeletal development and maintenance and are deregulated in many skeletal disorders. Hence our findings may offer the unique opportunity to uncover new molecular mechanisms through which FGF pathways regulate skeletal development and maintenance and to identify new targets for the treatment of FGF-related skeletal disorders. In this grant application we propose to study the role played by the different FGF ligands and receptors on autophagy regulation and to investigate the physiological relevance of these findings in the context of skeletal growth, homeostasis and maintenance. We will also investigate the intracellular machinery that links FGF signalling pathways to the regulation of autophagy. In addition, we generated preliminary data showing an impairment of autophagy in chondrocyte models of Achondroplasia (ACH) and Thanathoporic dysplasia, two skeletal disorders caused by mutations in FGFR3. We propose to study the role of autophagy in the pathogenesis of FGFR3-related dwarfisms and explore the pharmacological modulation of autophagy as new therapeutic approach for achondroplasia. This application, which combines cell biology, mouse genetics and pharmacological approaches, has the potential to shed light on new mechanisms involved in organismal development and homeostasis, which could be targeted to treat bone and cartilage diseases.

1 586 430 €

Start date: 2017-01-01, End date: 2022-06-30

Challenging the notion of Fortress Europe , the research investigates relations between the European Union and its southern periphery through the concept of borderlands . The concept emphasises the disaggregation of the triple function of borders demarcating state territory, authority, and national identity inherent in the Westphalian model of statehood. This process is most visible in (although not limited to) Europe, where integration has led to supranational areas of sovereignty, an internal market, a common currency, and a zone of free movement of people, each with a different territorial span. The project explores the complex and differentiated process by which the EU extends its unbundled functional and legal borders to the so-called southern Mediterranean (North Africa and parts of the Middle East), thereby transforming it into borderlands . They connect the European core with the periphery through various legal and functional border regimes, governance patterns, and the selective outsourcing of some EU border control duties. The overarching questions informing this research is whether, first, the borderland policies of the EU, described by some as a neo-medieval empire, is a functional consequence of the specific integration model pursued inside the EU, a matter of foreign policy choice or a local manifestation of a broader global phenomenon. Second, the project addresses the question of power dynamics that underwrite borderland governance, presuming a growing leverage of third country governments resulting from their co-optation as gatekeepers. Thus, while adopting an innovative approach, the project will enhance our understanding of EU-Mediterranean relations while also addressing crucial theoretical questions in international relations.

1 353 920 €

Start date: 2011-10-01, End date: 2017-03-31

Exchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions. We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour. To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency. We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.

2 370 250 €

Start date: 2016-12-01, End date: 2022-05-31

Chronic pain (CP) is a medical condition affecting around 20% of adults in Europe, characterised by an abnormal duration of pain (> 12 weeks) originally initiated by a trauma or illness. Despite significant progress, CP remains extremely hard to treat, with only one-third to two-thirds of patients reporting adequate some pain relief. This situation is even worse for neuropathic pain (NP), a specific class of CP affecting 8% of global population and whose origin mostly depend on peripheral or central nervous damage or disorder, which leads the brain to interpret as pain normally non painful stimuli. NP is difficult to treat due to the large number of entities involved (cells, genes and proteins working in synergy), which makes it hard to rapidly diagnose the exact cause of pain. Drugs targeting the central nervous system (e.g. antidepressants and opioids) provide only partial pain relief and are nonspecific, also causing side effects like addiction, and nausea, thus restraining their adoption for prolonged treatments. BREAK is the first non-invasive inhibitory optogenetic tool specifically designed for NP treatment, with potential application to the whole spectrum of CP. BREAK is composed of a drug and an optical device. The protein BLINK2 is injected in the painful area using a genetically engineered virus, and respond to a specific blue light by silencing the addressed neuron. The lamp can be kept at some distance (cm) from the skin and no implant is required. Just some minutes of treatment results in hours of pain relief, making the invasiveness of BREAK far lower than actually existing solution. A first version of BREAK has already demonstrated in in-vivo experiments on rats. During this project we plan to further develop the treatment and explore its commercial potential. In particular, leveraging from the experience of different partners, we will constitute a fruitful stakeholder network, including Academic centers, hospitals, pharma companies and investor

150 000 €

Start date: 2019-12-01, End date: 2021-11-30

Fluorescence single-molecule (SM) detection techniques have the potential to provide insights into the complex functions, structures and interactions of individual, specifically labelled biomolecules. However, current SM techniques work properly only when the biomolecule is observed in controlled environments, e.g., immobilized on a glass surface. Observation of biomolecular processes in living (multi)cellular environments – which is fundamental for sound biological conclusion – always comes with a price, such as invasiveness, limitations in the accessible information and constraints in the spatial and temporal scales. The overall objective of the BrightEyes project is to break the above limitations by creating a novel SM approach compatible with the state-of-the-art biomolecule-labelling protocols, able to track a biomolecule deep inside (multi)cellular environments – with temporal resolution in the microsecond scale, and with hundreds of micrometres tracking range – and simultaneously observe its structural changes, its nano- and micro-environments. Specifically, by exploring a novel single-photon detectors array, the BrightEyes project will implement an optical system, able to continuously (i) track in real-time the biomolecule of interest from which to decode its dynamics and interactions; (ii) measure the nano-environment fluorescence spectroscopy properties, such as lifetime, photon-pair correlation and intensity, from which to extract the biochemical properties of the nano-environment, the structural properties of the biomolecule – via SM-FRET and anti-bunching – and the interactions of the biomolecule with other biomolecular species – via STED-FCS; (iii) visualize the sub-cellular structures within the micro-environment with sub-diffraction spatial resolution – via STED and image scanning microscopy. This unique paradigm will enable unprecedented studies of biomolecular behaviours, interactions and self-organization at near-physiological conditions.

1 861 250 €

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

"Photovoltaics (PV) based on Silicon (Si) semiconductors is one the most growing technology in the World for renewable, sustainable, non-polluting, widely available clean energy sources. Theoretical and applied research aims at increasing the conversion efficiency of PV modules and their lifetime. The Si crystalline microstructure has an important role on both issues. Grain boundaries introduce additional resistance and reduce the conversion efficiency. Moreover, they are prone to microcracking, thus influencing the lifetime. At present, the existing standard qualification tests are not sufficient to provide a quantitative definition of lifetime, since all the possible failure mechanisms are not accounted for. In this proposal, an innovative computational approach to design and durability assessment of PV modules is put forward. The aim is to complement real tests by virtual (numerical) simulations. To achieve a predictive stage, a challenging multi-field (multi-physics) computational approach is proposed, coupling the nonlinear elastic field, the thermal field and the electric field. To model real PV modules, an adaptive multi-scale and multi-field strategy will be proposed by introducing error indicators based on the gradients of the involved fields. This numerical approach will be applied to determine the upper bound to the probability of failure of the system. This statistical assessment will involve an optimization analysis that will be efficiently handled by a Mathematica-based hybrid symbolic-numerical framework. Standard and non-standard experimental testing on Si cells and PV modules will also be performed to complement and validate the numerical approach. The new methodology based on the challenging integration of advanced physical and mathematical modelling, innovative computational methods and non-standard experimental techniques is expected to have a significant impact on the design, qualification and lifetime assessment of complex PV systems."

1 483 980 €

Start date: 2012-12-01, End date: 2017-11-30

The quantum technology revolution promises a transformational impact on the society and economics worldwide. It will enable breakthrough advancements in such diverse fields as secure communications, computing, metrology, and imaging. Quantum photonics, which recently received an incredible boost by the use of integrated optical circuits, is an excellent technological platform to enable such revolution, as it already plays a relevant role in many of the above applications. However, some major technical roadblocks needs to be overcome. Currently, the various components required for a complete quantum photonic system are produced on very different materials by dedicated fabrication technologies, as no single material is able to fulfil all the requirements for single-photon generation, manipulation, storage and detection. This project proposes a new hybrid approach for integrated quantum photonic systems based on femtosecond laser microfabrication (FLM), enabling the innovative miniaturization of various components on different materials, but with a single tool and with very favourable integration capabilities. This project will mainly focus on two major breakthroughs: the first one will be increasing the complexity achievable in the photonic platform and demonstrating unprecedented quantum computation capability; the second one will be the integration in the platform of multiple single-photon quantum memories and their interconnection. Achievement of these goals will only be possible by taking full advantage of the unique features of FLM, from the possibility to machine very different materials, to the 3D capabilities in waveguide writing and selective material removal. The successful demonstration and functional validation of this hybrid, integrated photonic platform will represent a significant leap for photonic microsystems in quantum computing and quantum communications.

2 381 875 €

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

We propose the development of novel nanodevices, such as nanoscale bridges and nanovectors, based on functionalized carbon nanotubes (CNT) for manipulating neurons and neuronal network activity in vitro. The main aim is to put forward innovative solutions that have the potential to circumvent the problems currently faced by spinal cord lesions or by neurodegenerative diseases. The unifying theme is to use recent advances in chemistry and nanotechnology to gain insight into the functioning of hybrid neuronal/CNT networks, relevant for the development of novel implantable devices to control neuronal signaling and improve synapse formation in a controlled fashion. The proposal s core strategy is to exploit the expertise of the PI in the chemical control of CNT properties to develop devices reaching various degrees of functional integration with the physiological electrical activity of cells and their networks, and to understand how such global dynamics are orchestrated when integrated by different substrates. An unconventional strategy will be represented by the electrical characterization of micro and nano patterned substrates by AFM and conductive tip AFM, both before and after neurons have grown on the substrates. We will also use the capability of AFM to identify critical positions in the neuronal network, while delivering time-dependent chemical stimulations. We will apply nanotechnology to contemporary neuroscience in the perspective of novel neuro-implantable devices and drug nanovectors, engineered to treat neurological and neurodegenerative lesions. The scientific strategy at the core of the proposal is the convergence between nanotechnology, chemistry and neurobiology. Such convergence, beyond helping understand the functioning and malfunctioning of the brain, can stimulate further research in this area and may ultimately lead to a new generation of nanomedicine applications in neurology and to new opportunities for the health care industry.

2 500 000 €

Start date: 2009-02-01, End date: 2014-01-31

The Virtual Element Method (VEM) is a novel technology for the discretization of partial differential equations (PDEs), that shares the same variational background as the Finite Element Method. First but not only, the VEM responds to the strongly increasing interest in using general polyhedral and polygonal meshes in the approximation of PDEs without the limit of using tetrahedral or hexahedral grids. By avoiding the explicit integration of the shape functions that span the discrete space and introducing an innovative construction of the stiffness matrixes, the VEM acquires very interesting properties and advantages with respect to more standard Galerkin methods, yet still keeping the same coding complexity. For instance, the VEM easily allows for polygonal/polyhedral meshes (even non-conforming) with non-convex elements and possibly with curved faces; it allows for discrete spaces of arbitrary C^k regularity on unstructured meshes. The main scope of the project is to address the recent theoretical challenges posed by VEM and to assess whether this promising technology can achieve a breakthrough in applications. First, the theoretical and computational foundations of VEM will be made stronger. A deeper theoretical insight, supported by a wider numerical experience on benchmark problems, will be developed to gain a better understanding of the method's potentials and set the foundations for more applicative purposes. Second, we will focus our attention on two tough and up-to-date problems of practical interest: large deformation elasticity (where VEM can yield a dramatically more efficient handling of material inclusions, meshing of the domain and grid adaptivity, plus a much stronger robustness with respect to large grid distortions) and the cardiac bidomain model (where VEM can lead to a more accurate domain approximation through MRI data, a flexible refinement/de-refinement procedure along the propagation front, to an exact satisfaction of conservation laws).

980 634 €

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

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: 2023-08-31

Conformal Field Theory (CFT) was originally conceived in four and three dimensions, with applications to particle physics and critical phenomena in mind. However, it is in two dimensions that the most spectacular results have been obtained. In higher dimensions, there used to be a general feeling that the constraining power of conformal symmetry by itself is insufficient to tell nontrivial things about the dynamics. Hence the interest in various additional assumptions. This is not fully satisfactory, since there are likely many CFTs that do not fulfill any of them. The main focus of this proposal is to take a fresh look at the idea that the mathematical structure of CFTs is instead such a strong constraint that it can allow for a complete solution of the theory. This program, known as conformal bootstrap, has provided a new element in the quantum field theory toolbox to describe genuine non-perturbative cases. This project aims to explore new directions and push forward the frontiers of conformal filed theories, with the ultimate objective of a detailed classification and understanding of scale invariant systems and their properties. CFT-MAP will develop more efficient numerical techniques and complementary analytical tools making use of two main methods: by studying correlation functions of operators present in any quantum field theory, such as global symmetry conserved currents and the energy momentum tensor; by inspecting the analytical structure of correlation functions. The project will scan the landscape of CFTs, identifying where and how they exist. By significantly improving over the methods at disposal, this proposal will be able to study theories currently are out of reach. Besides the innovative methodologies, a fundamental outcome of CFT-MAP will be a word record determination of critical exponents in second phase transition, together with additional information that allows an approximate reconstruction of the QFT in the neighborhood of fixed points.

1 500 000 €

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

This proposal aims at bringing to the market a revolutionary device to uniquely identify the chirality of molecules. An object is chiral if it differs from its mirror image, like our left and right hands. Chirality plays an extremely important role in two main fields: (1) Many drugs are chiral and selecting one of the two forms often enables the pharma industry to extend patent franchise, thus increasing profitability, and to improve the quality, safety and efficacy of the drug. (2) Researchers in the chemistry and biophysics labs use chirality as an indication of the 3D structural conformation of proteins and DNA, to study e.g. their secondary structure and stability under external stimuli. Spectrometers for measuring chirality already exist in the market. Many customers in the two aforementioned sectors could be interested in the new product we propose because it presents several advantages, namely a 2-fold reduction of the price, a 4-fold shrinking of the footprint and an increased information content. The ground-breaking concept (under patenting) behind this new spectrometer is to employ an ultra-stable interferometer to measure the chiral spectrum of molecules via a Fourier-transform approach and a heterodyne amplification of the signal. A first working prototype has already been realized and tested. The CHIMERA project has two main goals. (1) We aim at unleashing the innovation potential of the approach, by technically validating two prototypes in a pharmaceutical company and a biochemistry research lab, thus pushing the Technology Readiness Level of the system to the ultimate maturity required to approach the market, corresponding to TRL9. (2) We will design a complete exploitation plan, performing a thorough analysis of the market, developing a financing strategy, benchmarking our instrument against the competitors’ ones, profiling strategic partners and drafting a first version of a Business Plan to decide on the opportunity to found a start-up company.

149 375 €

Start date: 2017-05-01, End date: 2018-10-31

The developing world has been plagued by many civil conflicts in the past thirty years. Understanding the roots and the consequences of these conflicts is crucial to fight poverty. This project will take an economic approach to investigate the interplay between cultural, political and economic determinants of conflict in poor countries. I will assess the role of domestic and international factors. Domestic factors include variables such as cultural identity, income inequality, resource endowments and geography. I will re-examine the role of ethnic diversity using original multi-dimensional indicators. These take into account that the salience of ethnic identity may depend on how much it overlaps with categories based on income, education, etc. I will also re-assess the role of natural resource abundance from a theoretical and empirical standpoint. I will develop a theory of how rebel groups are organized drawing on the theory of incentives and test it using detailed geographic information on the location of mineral deposits in Africa. I will also analyze the role of international players using a methodology based on financial markets’ reactions to news. This methodology will allow me to address questions such as: Which companies gain or lose from violent conflict? How can we detect violations of international embargoes? What are the private incentives of complying with international norms, i.e. can reputation costs be quantified? These are questions of paramount importance from a policy perspective and on which almost no academic research exists in economics. Overall, the project should help integrate economic, social and political explanations for the occurrence of conflict in developing countries. I expect that its outcome should comprise the creation of new datasets, propose new methodological tools and offer some insights for designing economic policies to prevent conflict and fight poverty.

429 480 €

Start date: 2008-06-01, End date: 2013-05-31

Organized crime is systematically associated with lower economic development and higher corruption, political instability and political violence across countries. However, causal evidence on the economic and political effects of organized crime remains limited. The present proposal advances our knowledge of organized crime in two main directions. First, I will explore the effects of organized crime on the allocation and effectiveness of public spending, focusing on two important areas of government spending: public procurement and public subsidies to private firms. This analysis will advance our knowledge of the practices through which captured politicians can distort the allocation of resources in favour of criminal organizations, their implications for the efficiency of government intervention, and the effectiveness of alternative policy responses. Second, whilst previous research has focused almost exclusively on the traditional areas of origin of criminal organizations, I will study the effects of criminal groups moving to new regions and countries. I will focus in particular on three different contexts: i) the “transplant” of criminal organizations from southern to northern Italian regions; ii) interactions of immigrants and natives in criminal activity in the wake of recent migration to the Netherlands; and iii) the inflow of members of the Sicilian Mafia into the US during the period of alcohol prohibition (1920-1933). The present proposal will advance our understanding of how criminal groups can relocate to new regions and countries; their interactions with the criminal groups that may already be present there; and the economic and social effects in the areas of destination. From a methodological perspective, all projects will take advantage of unique micro-level data and state-of-the-art econometric methods for impact evaluation to provide clean evidence on causal relationships.

1 770 838 €

Start date: 2020-03-01, End date: 2025-02-28

The ClustersXCosmo ERC Starting Grant proposal has the goal of investigating the role of Galaxy Clusters as a cosmological probe and of exploiting the strong synergies between observational cosmology, galaxy formation and fundamental physics related to the tracers of the extreme peaks in the matter density field. In the last decade, astronomical data-sets have started to be widely and quantitatively used by the scientific community to address important physical questions such as: the nature of the dark matter and dark energy components and their evolution; the physical properties of the baryonic matter; the variation of fundamental constants over cosmic time; the sum of neutrino masses; the interplay between the galaxy population and the intergalactic medium; the nature of gravity over megaparsec scales and over cosmic times; the temperature evolution of the Universe. Most of these results are based on well-established geometrical cosmological probes (e.g., galaxies, supernovae, cosmic microwave background). Galaxy clusters provide a complementary and necessary approach, as their distribution as a function of time and observables is sensitive to both the geometrical and the dynamical evolution of the Universe, driven by the growth of structures. Among different cluster surveys, Sunyaev Zel'Dovich effect (SZE) detected catalogs have registered the most dramatic improvement over the last ~5 years, yielding samples extending up to the earliest times these systems appeared. This proposal aims at using a combination of the best available SZE cluster surveys and to interpret them by means of state-of-the-art computational facilities in order to firmly establish the yet controversial role of Galaxy Clusters as a probe for cosmology, fundamental physics and astrophysics. The timely convergence of current and next generation multi-wavelength surveys (DES/SPT/Planck/eRosita/Euclid) will be important to establish the role of Galaxy Clusters as a cosmological tool.

1 230 403 €

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

When two solutions with different composition are mixed, free energy of mixing is released. This phenomenon was deeply investigated in the last decades in order to harvest the so-called salinity gradient power. One of the most incipient technology that allows to harvest this energy is the Capacitive Mixing (CapMix) and its working mechanism is based on a fluidic electrochemical cell, similar to a supercapacitor. Since this mixing phenomenon holds true for both liquids and gases, my idea is to harvest energy from anthropic CO2. The energy density stored in the CO2 emission is tremendously higher than that stored in salinity gradient and theoretically estimated as high as 1570 TWh/year. Since ions are needed in CapMix process, with CO2CAP I propose for the first time to exploit a green ionic liquid (IL), i.e. a bio-derived molten salt at room temperature, both as electrolyte and CO2 absorbing medium in a CapMix cell. The principle consists of flowing a concentrated CO2 gas stream, alternated to vacuum step, in the IL during the charging/discharging of two electrodes. The CO2 will induce an electric double layer (EDL) expansion of charges at the electrode/IL interface thereby converting the released mixing energy into electrical energy. To reach this goal, the objectives of CO2CAP are to develop novel cutting-edge carbon-based electrodes and amino acid-based IL designed to maximize the EDL of charges at the electrode/IL interface, enhancing at the same time the CO2 absorption capacity. This will be possible by using a multidisciplinary approach based on materials engineering, modelling, advanced characterization methods and novel architecture of the electrodes. The engineered materials and cell will allow to demonstrate the feasibility of this new electrochemical approach, enabling a deeper understanding of the physical and electrochemical phenomena occurring in such a complicated system, and paving the way to a new generation of CO2-free renewable energy source.

1 497 500 €

Start date: 2021-01-01, End date: 2025-12-31

In COBRAS we will establish Femtosecond Covariance Spectroscopy, a new spectroscopic technique to measure the optical response of material which is based on stochastic light pulses characterized by frequency uncorrelated intensity fluctuation. By using light with different property every repetition, each reiteration of the experiment can be considered as a measurement under new conditions rather than a repetition of the same experiment. Crucially, within the ERC_StG project INCEPT we have demonstrated that in this limit the frequency of the Raman modes of a sample can be retrieved by measuring the spectral correlations in different pulses which are induced by the interaction with the sample. This is in striking contrast with standard approaches to Raman spectroscopy which are based on the measurement of the integrated emission of Raman sidebands at a given frequency and therefore require a high stability and low noise detection which can be reached only at a significant expense. Conversely, in covariance-based methods noise is a resource that can be exploited (rather than an impediment) and a much simpler and cheaper architecture for the spectrometer can be envisioned. The central idea of COBRAS is to set the way for commercial exploitation of covariance-based approaches to Raman spectroscopy. To this purpose we will develop a prototype spectrometer, study the general applicability of the covariance based methods and identify viable strategies for the commercialization of the spectrometer developed. We stress that the concept proposed here for Raman spectroscopy can be extended to different optical techniques and wavelength ranges. This make us confident that the COBRAS investment may represent a paradigmatic change in the approach to optical spectroscopy, potentially disclosing a new market across different industrial and scientific spectroscopic applications.

150 000 €

Start date: 2019-07-01, End date: 2021-06-30

The latter part of the twentieth century was a period of rapid democratisation on a global scale. The attention of comparative politics scholars followed the progression of so-called Third Wave democracies, and gradually progressed from the study of the causes of and the transitions to democracy to the problems of democratic consolidation, and then to more recent issues relating to the quality of democracy. A further, frontier step may now be added to such research path by focusing on a subject that has remained largely under-researched, if at all, namely the political, social and economic consequences that emerged in countries where real democratic change took place. The question of what democracy has been able to deliver will become ever more relevant to the future prospects of recent democratisation processes and of democracy at large. In the study of the consequences of democratisation, the advent of democracy is thus no longer observed as an endpoint, or a dependent variable to be explained, but as a starting point, or an independent variable that allegedly contributes to the explanation of a wide range of political, economic and social effects. The question of the corollaries of democratisation also has crucial policy implications. The goals of the proposed research are: a) the definition of a theoretical framework that articulates, integrates and interrelates the different existing hypotheses and arguments on the consequences of democratization processes b) the empirical investigation, through a combination and integration of quantitative and qualitative methods, of the validity of three specific such hypotheses, namely: i. democratisation favours the consolidation of the state (as a political effect) ii. democratisation favours economic liberalization (as an economic effect) iii. democratisation improves social welfare (as a social effect) c) the analysis of the specific forms that the effects of democratization assume in different world regions

322 284 €

Start date: 2010-11-01, End date: 2015-10-31