Project acronym 4DPHOTON
Project Beyond Light Imaging: High-Rate Single-Photon Detection in Four Dimensions
Researcher (PI) Massimiliano FIORINI
Host Institution (HI) ISTITUTO NAZIONALE DI FISICA NUCLEARE
Call Details Consolidator Grant (CoG), PE2, ERC-2018-COG
Summary 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.
Summary
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.
Max ERC Funding
1 975 000 €
Duration
Start date: 2019-12-01, End date: 2024-11-30
Project acronym A-FRO
Project Actively Frozen - contextual modulation of freezing and its neuronal basis
Researcher (PI) Marta de Aragão Pacheco Moita
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Summary
When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Max ERC Funding
1 969 750 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym AN-ICON
Project An-Iconology: History, Theory, and Practices of Environmental Images
Researcher (PI) Andrea PINOTTI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Call Details Advanced Grant (AdG), SH5, ERC-2018-ADG
Summary "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.
"
Summary
"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.
"
Max ERC Funding
2 328 736 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym AST
Project Automatic System Testing
Researcher (PI) Leonardo MARIANI
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary 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.
Summary
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.
Max ERC Funding
150 000 €
Duration
Start date: 2019-01-01, End date: 2020-06-30
Project acronym ASTAOMEGA
Project IMPLEMENTATION OF A SUSTAINABLE AND COMPETITIVE SYSTEM TO SIMULTANEOUSLY PRODUCE ASTAXANTHIN AND OMEGA-3 FATTY ACIDS IN MICROALGAE FOR ACQUACULTURE AND HUMAN NUTRITION
Researcher (PI) Matteo BALLOTTARI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI VERONA
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary This project aims at developing an innovative and commercially competitive production platform for high value products as Astaxanthin and Omega-3, to be used for human nutrition or aquaculture.
Astaxanthin is a pigment primary produced by microalgae: this carotenoid has a strong antioxidant power and it is used in different fields as healthcare, food/feed supplementation and as pigmenting agent in aquaculture. However, cultivation of the main microalgae species producing Astaxanthin is costly due to low biomass productivity or low Astaxanthin content, causing an extremely high price of this molecule on the market.
Marine microalgae are also the primary producers of Omega-3, very long chain fatty acids, essential components of high quality diets for humans, being related to cardiovascular wellness, and proper visual and cognitive development. However, due to the high cost of microalgae cultivation, the market of Omega-3 is mostly based on fish or krill oils, with high costs and environment impacts associated.
New sources of Astaxanthin and Omega-3 must thus be implemented: based on the results obtained in ERC-Stg-SOLENALGAE, an innovative, low cost and high productive strategy can be proposed for simultaneous Astaxanthin and Omega-3 production in the robust and fast growing marine microalgae species Nannochloropsis gaditana.
The main objectives of the ASTAOMEGA project will be:
1. To validate to a demonstration stage the ASTAOMEGA system
2. The assessment of the market size and market requirements, through extensive market analysis
3. The identification of the best suitable commercial route to be undertaken to take the ASTAOMEGA system to the market, as inception of a spin-off company and/or the licensing agreements on the IPR exploitation with the interested end-users (see LOIs).
The ASTAOMEGA team is confident that the outcomes of this project are poised to exert a beneficial impact on the European microalgae industry and nutraceuticals market
Summary
This project aims at developing an innovative and commercially competitive production platform for high value products as Astaxanthin and Omega-3, to be used for human nutrition or aquaculture.
Astaxanthin is a pigment primary produced by microalgae: this carotenoid has a strong antioxidant power and it is used in different fields as healthcare, food/feed supplementation and as pigmenting agent in aquaculture. However, cultivation of the main microalgae species producing Astaxanthin is costly due to low biomass productivity or low Astaxanthin content, causing an extremely high price of this molecule on the market.
Marine microalgae are also the primary producers of Omega-3, very long chain fatty acids, essential components of high quality diets for humans, being related to cardiovascular wellness, and proper visual and cognitive development. However, due to the high cost of microalgae cultivation, the market of Omega-3 is mostly based on fish or krill oils, with high costs and environment impacts associated.
New sources of Astaxanthin and Omega-3 must thus be implemented: based on the results obtained in ERC-Stg-SOLENALGAE, an innovative, low cost and high productive strategy can be proposed for simultaneous Astaxanthin and Omega-3 production in the robust and fast growing marine microalgae species Nannochloropsis gaditana.
The main objectives of the ASTAOMEGA project will be:
1. To validate to a demonstration stage the ASTAOMEGA system
2. The assessment of the market size and market requirements, through extensive market analysis
3. The identification of the best suitable commercial route to be undertaken to take the ASTAOMEGA system to the market, as inception of a spin-off company and/or the licensing agreements on the IPR exploitation with the interested end-users (see LOIs).
The ASTAOMEGA team is confident that the outcomes of this project are poised to exert a beneficial impact on the European microalgae industry and nutraceuticals market
Max ERC Funding
149 955 €
Duration
Start date: 2018-09-01, End date: 2020-02-29
Project acronym B Massive
Project Binary massive black hole astrophysics
Researcher (PI) Alberto SESANA
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Call Details Consolidator Grant (CoG), PE9, ERC-2018-COG
Summary 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.
Summary
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.
Max ERC Funding
1 532 750 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym BBBhybrid
Project Advanced in vitro physiological models: Towards real-scale, biomimetic and biohybrid barriers-on-a-chip
Researcher (PI) Gianni CIOFANI
Host Institution (HI) FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary This project is focused on the design, the production, the characterization, and the proposal for future commercialization of the first 1:1 scale 3D-printed realistic model of the brain tumor microenvironment with its associated blood neurovasculature. The proposed biomimetic dynamic 3D system, characterized by microcapillary diameter size and fluid flows similar to the in vivo physiological parameters, represents a drastic innovation with respect to other models well-established in the literature and available on the market, since it will allow to reliably reproduce the physiological environment and to accurately estimate the amount of drugs and/or of nanomaterial-associated compounds delivered through a modular length of the system. At the same time, in vitro 3D models are envisioned, allowing more physiologically-relevant information and predictive data to be obtained. All the artificial components will be fabricated through advanced lithography techniques based on two-photon polymerization (2pp), a disrupting mesoscale manufacturing approach which allows the fast fabrication of low-cost structures with nanometer resolution and great levels of reproducibility/accuracy. The proposed platform can be easily adopted in cell biology laboratories as multi-compartmental scaffold for the development of advanced co-culture systems, the primary biomedical applications of which consist in high-throughput screening of brain drugs and in testing of the efficacy of different anticancer therapies in vitro.
Summary
This project is focused on the design, the production, the characterization, and the proposal for future commercialization of the first 1:1 scale 3D-printed realistic model of the brain tumor microenvironment with its associated blood neurovasculature. The proposed biomimetic dynamic 3D system, characterized by microcapillary diameter size and fluid flows similar to the in vivo physiological parameters, represents a drastic innovation with respect to other models well-established in the literature and available on the market, since it will allow to reliably reproduce the physiological environment and to accurately estimate the amount of drugs and/or of nanomaterial-associated compounds delivered through a modular length of the system. At the same time, in vitro 3D models are envisioned, allowing more physiologically-relevant information and predictive data to be obtained. All the artificial components will be fabricated through advanced lithography techniques based on two-photon polymerization (2pp), a disrupting mesoscale manufacturing approach which allows the fast fabrication of low-cost structures with nanometer resolution and great levels of reproducibility/accuracy. The proposed platform can be easily adopted in cell biology laboratories as multi-compartmental scaffold for the development of advanced co-culture systems, the primary biomedical applications of which consist in high-throughput screening of brain drugs and in testing of the efficacy of different anticancer therapies in vitro.
Max ERC Funding
150 000 €
Duration
Start date: 2019-04-01, End date: 2020-09-30
Project acronym bECOMiNG
Project spontaneous Evolution and Clonal heterOgeneity in MoNoclonal Gammopathies: from mechanisms of progression to clinical management
Researcher (PI) Niccolo Bolli
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Call Details Consolidator Grant (CoG), LS7, ERC-2018-COG
Summary As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
Summary
As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
Max ERC Funding
1 998 781 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym BIT-ACT
Project Bottom-up initiatives and anti-corruption technologies: how citizens use ICTs to fight corruption
Researcher (PI) Alice Mattoni
Host Institution (HI) ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA
Call Details Starting Grant (StG), SH2, ERC-2018-STG
Summary Corruption is a global challenge that affects the lives of millions of citizens. In the past decade, Information and Communication Technologies (ICTs) have become indispensable tools in the fight to reduce corruption, especially when employed from the bottom-up by civil society organizations. While pioneering initiatives in this direction have flourished, to date we only have unsystematic and descriptive evidence regarding how they work and the associated consequences. With the objective of significantly advancing knowledge on this topic, BIT-ACT will open a new line of inquiry by investigating what I call anti-corruption technologies (ACTs) to: (1) assess how civil society organizations engage with ACTs to counter corruption, (2) appraise how ACTs enable intersections between bottom-up and top-down efforts against corruption, and (3) evaluate how ACTs blend with the transnational dimension in the struggle against corruption. Based on an interdisciplinary framework that combines corruption studies, science and technology studies and social movement studies, BIT-ACT will use the constructivist grounded theory method to analyze a combination of textual and visual data in a comparative and transnational research design including nine countries – Algeria, Bangladesh, Brazil, Estonia, India, Italy, Spain, Ukraine, Uruguay. BIT-ACT will be groundbreaking in three ways. At the theoretical level, it will expand the debate on anti-corruption providing grounded concepts and models to explain ACTs; at the empirical level, it will advance knowledge on how the usage of ACTs is changing the relationship between citizens and democratic institutions; at the methodological level, it will innovate in the use of grounded theory assessing a new standard for cross-national comparative grounded theory. Finally, BIT-ACT will produce sound and useful knowledge for the stakeholders involved in the fight against corruption worldwide by suggesting how to best employ ICTs from the bottom-up.
Summary
Corruption is a global challenge that affects the lives of millions of citizens. In the past decade, Information and Communication Technologies (ICTs) have become indispensable tools in the fight to reduce corruption, especially when employed from the bottom-up by civil society organizations. While pioneering initiatives in this direction have flourished, to date we only have unsystematic and descriptive evidence regarding how they work and the associated consequences. With the objective of significantly advancing knowledge on this topic, BIT-ACT will open a new line of inquiry by investigating what I call anti-corruption technologies (ACTs) to: (1) assess how civil society organizations engage with ACTs to counter corruption, (2) appraise how ACTs enable intersections between bottom-up and top-down efforts against corruption, and (3) evaluate how ACTs blend with the transnational dimension in the struggle against corruption. Based on an interdisciplinary framework that combines corruption studies, science and technology studies and social movement studies, BIT-ACT will use the constructivist grounded theory method to analyze a combination of textual and visual data in a comparative and transnational research design including nine countries – Algeria, Bangladesh, Brazil, Estonia, India, Italy, Spain, Ukraine, Uruguay. BIT-ACT will be groundbreaking in three ways. At the theoretical level, it will expand the debate on anti-corruption providing grounded concepts and models to explain ACTs; at the empirical level, it will advance knowledge on how the usage of ACTs is changing the relationship between citizens and democratic institutions; at the methodological level, it will innovate in the use of grounded theory assessing a new standard for cross-national comparative grounded theory. Finally, BIT-ACT will produce sound and useful knowledge for the stakeholders involved in the fight against corruption worldwide by suggesting how to best employ ICTs from the bottom-up.
Max ERC Funding
1 489 115 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym BrainCircuit-on-chip
Project Microfluidic chambers for establishing physiological and pathological human iPSC-derived neuronal circuits
Researcher (PI) Vania BROCCOLI
Host Institution (HI) OSPEDALE SAN RAFFAELE SRL
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary In vitro cultures of brain cells generate an ease and accessible ensemble of neurons In vitro cultures of brain cells generate an ease and accessible ensemble of neurons which has been invaluable for innumerable cellular and molecular studies. However, brain tissue dissociation and neuronal plating in vitro causes a complete loss of the original connections present into the brain tissue. Therefore, in vitro neuronal cultures do not allow to model specific neuronal circuits and study their specific properties. The same limitation is valid for human stem cell-derived neuronal cell cultures. In fact, several neuronal cell types can be differentiated from human iPS cells (iPSCs), but without any organization in terms of connectivity or synaptic specificity. We have established a microfluidic platform, named BrainCircuit-on-chip, which allows to growth human iPSC-derived neurons with a stereotyped organization and to establish patterned connections between different neuronal cell types. These microchips contain a central chamber where synapses between the two neuronal cell types are generated establishing the correct functional integration between the two neuronal populations. PDMS-microfluidic chambers are transparent and enables high-power and time-lapse imaging in the different neuronal compartments for sub-cellular and molecular studies. Moreover, the design of the central chamber enables to expose the synapses to chemicals or other cells types like astrocytes or microglia to study their effects on a specific class of synapses. We will produce a convenient kit with the frozen human neurons, the microfluidic chamber and a detailed protocol for generating the patterned neuronal circuits for research studies, compound testing and toxicology research.
Summary
In vitro cultures of brain cells generate an ease and accessible ensemble of neurons In vitro cultures of brain cells generate an ease and accessible ensemble of neurons which has been invaluable for innumerable cellular and molecular studies. However, brain tissue dissociation and neuronal plating in vitro causes a complete loss of the original connections present into the brain tissue. Therefore, in vitro neuronal cultures do not allow to model specific neuronal circuits and study their specific properties. The same limitation is valid for human stem cell-derived neuronal cell cultures. In fact, several neuronal cell types can be differentiated from human iPS cells (iPSCs), but without any organization in terms of connectivity or synaptic specificity. We have established a microfluidic platform, named BrainCircuit-on-chip, which allows to growth human iPSC-derived neurons with a stereotyped organization and to establish patterned connections between different neuronal cell types. These microchips contain a central chamber where synapses between the two neuronal cell types are generated establishing the correct functional integration between the two neuronal populations. PDMS-microfluidic chambers are transparent and enables high-power and time-lapse imaging in the different neuronal compartments for sub-cellular and molecular studies. Moreover, the design of the central chamber enables to expose the synapses to chemicals or other cells types like astrocytes or microglia to study their effects on a specific class of synapses. We will produce a convenient kit with the frozen human neurons, the microfluidic chamber and a detailed protocol for generating the patterned neuronal circuits for research studies, compound testing and toxicology research.
Max ERC Funding
150 000 €
Duration
Start date: 2019-08-01, End date: 2021-01-31
