Project acronym AMDROMA
Project Algorithmic and Mechanism Design Research in Online MArkets
Researcher (PI) Stefano LEONARDI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Country Italy
Call Details Advanced Grant (AdG), PE6, ERC-2017-ADG
Summary Online markets currently form an important share of the global economy. The Internet hosts classical markets (real-estate, stocks, e-commerce) as well allowing new markets with previously unknown features (web-based advertisement, viral marketing, digital goods, crowdsourcing, sharing economy). Algorithms play a central role in many decision processes involved in online markets. For example, algorithms run electronic auctions, trade stocks, adjusts prices dynamically, and harvest big data to provide economic information. Thus, it is of paramount importance to understand the algorithmic and mechanism design foundations of online markets.
The algorithmic research issues that we consider involve algorithmic mechanism design, online and approximation algorithms, modelling uncertainty in online market design, and large-scale data analysisonline and approximation algorithms, large-scale optimization and data mining. The aim of this research project is to combine these fields to consider research questions that are central for today's Internet economy. We plan to apply these techniques so as to solve fundamental algorithmic problems motivated by web-basedInternet advertisement, Internet market designsharing economy, and crowdsourcingonline labour marketplaces. While my planned research is focussedcentered on foundational work with rigorous design and analysis of in algorithms and mechanismsic design and analysis, it will also include as an important component empirical validation on large-scale real-life datasets.
Summary
Online markets currently form an important share of the global economy. The Internet hosts classical markets (real-estate, stocks, e-commerce) as well allowing new markets with previously unknown features (web-based advertisement, viral marketing, digital goods, crowdsourcing, sharing economy). Algorithms play a central role in many decision processes involved in online markets. For example, algorithms run electronic auctions, trade stocks, adjusts prices dynamically, and harvest big data to provide economic information. Thus, it is of paramount importance to understand the algorithmic and mechanism design foundations of online markets.
The algorithmic research issues that we consider involve algorithmic mechanism design, online and approximation algorithms, modelling uncertainty in online market design, and large-scale data analysisonline and approximation algorithms, large-scale optimization and data mining. The aim of this research project is to combine these fields to consider research questions that are central for today's Internet economy. We plan to apply these techniques so as to solve fundamental algorithmic problems motivated by web-basedInternet advertisement, Internet market designsharing economy, and crowdsourcingonline labour marketplaces. While my planned research is focussedcentered on foundational work with rigorous design and analysis of in algorithms and mechanismsic design and analysis, it will also include as an important component empirical validation on large-scale real-life datasets.
Max ERC Funding
1 780 150 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym BABE
Project Bodies across borders: oral and visual memory in Europe and beyond
Researcher (PI) Luisella Passerini
Host Institution (HI) EUROPEAN UNIVERSITY INSTITUTE
Country Italy
Call Details Advanced Grant (AdG), SH6, ERC-2011-ADG_20110406
Summary 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.
Summary
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.
Max ERC Funding
1 488 501 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym BRSCDP-TEA
Project Bounded rationality and social concerns in decision processes: theory, experiments, and applications
Researcher (PI) Massimo Marinacci
Host Institution (HI) UNIVERSITA COMMERCIALE LUIGI BOCCONI
Country Italy
Call Details Advanced Grant (AdG), SH1, ERC-2008-AdG
Summary In the field of economics, individual decision making is the basic building block for studying complex environments such as markets, political systems, and social dynamics. Individual decision making is embodied in the neoclassical economically rational agent, whose only concern is the maximization of utility from his own material consumption. Two qualities of this agent are especially important for the research we will undertake: He has perfect understanding of the problems he faces - today and in the future - and unbounded computational ability to solve them. He also has no regard for the consumption of other members of the society or for their feelings about his actions. Huge empirical and experimental evidence shows that departure from these qualities is robust and significant. The failure of the existing models to incorporate bounded rationality and social concerns has proven critical in socially relevant and complex situations such as lifetime consumption and saving, taxation and expenditure policy, labour search and wage determination. The objective of this project is to bring these phenomena into the framework of neoclassical economics, to test their implications, and to tackle important applications. A novel and central feature of our approach is the attempt to retain the parsimonious methodological approach of economic modelling, which has scored groundbreaking successes in matters such as the design of auctions, markets, contracts, and voting mechanisms. Our project envisions the development of theory on individual decision making, the use of experiments to illuminate and test the theory, and the concrete application of theory - mainly to financial markets. The project will push the frontiers of the understanding of the above mentioned socially relevant situations. The explanatory power of our approach will be guaranteed by the continuous feed-back between theory and evidence- experimental and neuroexperimental, and by a departure from ad hoc modelling.
Summary
In the field of economics, individual decision making is the basic building block for studying complex environments such as markets, political systems, and social dynamics. Individual decision making is embodied in the neoclassical economically rational agent, whose only concern is the maximization of utility from his own material consumption. Two qualities of this agent are especially important for the research we will undertake: He has perfect understanding of the problems he faces - today and in the future - and unbounded computational ability to solve them. He also has no regard for the consumption of other members of the society or for their feelings about his actions. Huge empirical and experimental evidence shows that departure from these qualities is robust and significant. The failure of the existing models to incorporate bounded rationality and social concerns has proven critical in socially relevant and complex situations such as lifetime consumption and saving, taxation and expenditure policy, labour search and wage determination. The objective of this project is to bring these phenomena into the framework of neoclassical economics, to test their implications, and to tackle important applications. A novel and central feature of our approach is the attempt to retain the parsimonious methodological approach of economic modelling, which has scored groundbreaking successes in matters such as the design of auctions, markets, contracts, and voting mechanisms. Our project envisions the development of theory on individual decision making, the use of experiments to illuminate and test the theory, and the concrete application of theory - mainly to financial markets. The project will push the frontiers of the understanding of the above mentioned socially relevant situations. The explanatory power of our approach will be guaranteed by the continuous feed-back between theory and evidence- experimental and neuroexperimental, and by a departure from ad hoc modelling.
Max ERC Funding
1 399 800 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym CARDIOEPIGEN
Project Epigenetics and microRNAs in Myocardial Function and Disease
Researcher (PI) Gianluigi Condorelli
Host Institution (HI) HUMANITAS MIRASOLE SPA
Country Italy
Call Details Advanced Grant (AdG), LS4, ERC-2011-ADG_20110310
Summary Heart failure (HF) is the ultimate outcome of many cardiovascular diseases. Re-expression of fetal genes in the adult heart contributes to development of HF. Two mechanisms involved in the control of gene expression are epigenetics and microRNAs (miRs). We propose a project on epigenetic and miR-mediated mechanisms leading to HF.
Epigenetics refers to heritable modification of DNA and histones that does not modify the genetic code. Depending on the type of modification and on the site affected, these chemical changes up- or down-regulate transcription of specific genes. Despite it being a major player in gene regulation, epigenetics has been only partly investigated in HF. miRs are regulatory RNAs that target mRNAs for inhibition. Dysregulation of the cardiac miR signature occurs in HF. miR expression may itself be under epigenetic control, constituting a miR-epigenetic regulatory network. To our knowledge, this possibility has not been studied yet.
Our specific hypothesis is that the profile of DNA/histone methylation and the cross-talk between epigenetic enzymes and miRs have fundamental roles in defining the characteristics of cells during cardiac development and that the dysregulation of these processes determines the deleterious nature of the stressed heart’s gene programme. We will test this first through a genome-wide study of DNA/histone methylation to generate maps of the main methylation modifications occurring in the genome of cardiac cells treated with a pro-hypertrophy regulator and of a HF model. We will then investigate the role of epigenetic enzymes deemed important in HF, through the generation and study of knockout mice models. Finally, we will test the possible therapeutic potential of modulating epigenetic genes.
We hope to further understand the pathological mechanisms leading to HF and to generate data instrumental to the development of diagnostic and therapeutic strategies for this disease.
Summary
Heart failure (HF) is the ultimate outcome of many cardiovascular diseases. Re-expression of fetal genes in the adult heart contributes to development of HF. Two mechanisms involved in the control of gene expression are epigenetics and microRNAs (miRs). We propose a project on epigenetic and miR-mediated mechanisms leading to HF.
Epigenetics refers to heritable modification of DNA and histones that does not modify the genetic code. Depending on the type of modification and on the site affected, these chemical changes up- or down-regulate transcription of specific genes. Despite it being a major player in gene regulation, epigenetics has been only partly investigated in HF. miRs are regulatory RNAs that target mRNAs for inhibition. Dysregulation of the cardiac miR signature occurs in HF. miR expression may itself be under epigenetic control, constituting a miR-epigenetic regulatory network. To our knowledge, this possibility has not been studied yet.
Our specific hypothesis is that the profile of DNA/histone methylation and the cross-talk between epigenetic enzymes and miRs have fundamental roles in defining the characteristics of cells during cardiac development and that the dysregulation of these processes determines the deleterious nature of the stressed heart’s gene programme. We will test this first through a genome-wide study of DNA/histone methylation to generate maps of the main methylation modifications occurring in the genome of cardiac cells treated with a pro-hypertrophy regulator and of a HF model. We will then investigate the role of epigenetic enzymes deemed important in HF, through the generation and study of knockout mice models. Finally, we will test the possible therapeutic potential of modulating epigenetic genes.
We hope to further understand the pathological mechanisms leading to HF and to generate data instrumental to the development of diagnostic and therapeutic strategies for this disease.
Max ERC Funding
2 500 000 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym CLEAR
Project Modulating cellular clearance to cure human disease
Researcher (PI) Andrea Ballabio
Host Institution (HI) FONDAZIONE TELETHON
Country Italy
Call Details Advanced Grant (AdG), LS2, ERC-2009-AdG
Summary Cellular clearance is a fundamental process required by all cells in all species. Important physiological processes, such as aging, and pathological mechanisms, such as neurodegeneration, are strictly dependent on cellular clearance. In eukaryotes, most of the cellular clearing processes occur in a specialized organelle, the lysosome. This project is based on a recent discovery, made in our laboratory, of a gene network, which we have named CLEAR, that controls lysosomal biogenesis and function and regulates cellular clearance. The specific goals of the project are: 1) the comprehensive characterization of the mechanisms underlying the CLEAR network, 2) the thorough understanding of CLEAR physiological function at the cellular and organism levels, 3) the development of strategies and tools to modulate cellular clearance, and 4) the implementation of proof-of-principle therapeutic studies based on the activation of the CLEAR network in murine models of human lysosomal storage disorders and of neurodegenerative diseases, such as Alzheimers s and Huntington s diseases. A combination of genomics, bioinformatics, systems biology, chemical genomics, cell biology, and mouse genetics approaches will be used to achieve these goals. Our goal is to develop tools to modulate cellular clearance and to use such tools to develop therapies to cure human disease. The potential medical relevance of this project is very high, particularly in the field of neurodegenerative disease. Therapies that prevent, ameliorate or delay neurodegeneration in these diseases would have a huge impact on human health.
Summary
Cellular clearance is a fundamental process required by all cells in all species. Important physiological processes, such as aging, and pathological mechanisms, such as neurodegeneration, are strictly dependent on cellular clearance. In eukaryotes, most of the cellular clearing processes occur in a specialized organelle, the lysosome. This project is based on a recent discovery, made in our laboratory, of a gene network, which we have named CLEAR, that controls lysosomal biogenesis and function and regulates cellular clearance. The specific goals of the project are: 1) the comprehensive characterization of the mechanisms underlying the CLEAR network, 2) the thorough understanding of CLEAR physiological function at the cellular and organism levels, 3) the development of strategies and tools to modulate cellular clearance, and 4) the implementation of proof-of-principle therapeutic studies based on the activation of the CLEAR network in murine models of human lysosomal storage disorders and of neurodegenerative diseases, such as Alzheimers s and Huntington s diseases. A combination of genomics, bioinformatics, systems biology, chemical genomics, cell biology, and mouse genetics approaches will be used to achieve these goals. Our goal is to develop tools to modulate cellular clearance and to use such tools to develop therapies to cure human disease. The potential medical relevance of this project is very high, particularly in the field of neurodegenerative disease. Therapies that prevent, ameliorate or delay neurodegeneration in these diseases would have a huge impact on human health.
Max ERC Funding
2 100 000 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym COGSYSTEMS
Project Understanding actions and intentions of others
Researcher (PI) Giacomo Rizzolatti
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PARMA
Country Italy
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.
Summary
How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.
Max ERC Funding
1 992 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym CompuLaw
Project Computable Law
Researcher (PI) Giovanni Sartor
Host Institution (HI) ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA
Country Italy
Call Details Advanced Grant (AdG), SH2, ERC-2018-ADG
Summary The project addresses the regulation of computations (processes and systems) through an innovative legal & technological framework: it provides epistemic, technical and normative guidance for the de-velopment of computable laws and law compliant computations.
The context is the ongoing transformation of the social world into a hybrid infosphere, populated by a huge and growing number of increasingly pervasive, autonomous and intelligent computational enti-ties. The scale, speed, ubiquity and autonomy of computations make it impossible for humans to di-rectly monitor them and anticipate all possible illegal computational behaviours. The law can hold the hybrid infosphere under its rule – providing protection, security and trust – only if it be-comes computation-oriented: legal and ethical requirements must be integrated with, mapped onto, and partially translated into, computable representations of legal knowledge and reasoning.
Current legal culture still has not adequately addressed risks and potentials of computable law. My project will fill this gap, providing concepts, principles, methods and techniques and normative guide-lines to support law-abiding computations. It has the normative purpose to uphold the principle of rule of law, translating legal norms and legal values into requirements for computable laws and legally-responsive computational agents. My project will provide major methodological and substantive breakthroughs. On the one hand, it pro-poses a socio-technical methodology for regulatory design and evaluation, integrating three discipli-nary clusters: a social-legal one, a philosophical-logical one and a computing-AI one. On the other hand, it develops a framework including: (a) norms, legal values and principles for developers, de-ployers and users; (b) languages and methods to specify requirements of computations and norms directed to them; (c) cognitive architectures for legally-responsive computational agents.
Summary
The project addresses the regulation of computations (processes and systems) through an innovative legal & technological framework: it provides epistemic, technical and normative guidance for the de-velopment of computable laws and law compliant computations.
The context is the ongoing transformation of the social world into a hybrid infosphere, populated by a huge and growing number of increasingly pervasive, autonomous and intelligent computational enti-ties. The scale, speed, ubiquity and autonomy of computations make it impossible for humans to di-rectly monitor them and anticipate all possible illegal computational behaviours. The law can hold the hybrid infosphere under its rule – providing protection, security and trust – only if it be-comes computation-oriented: legal and ethical requirements must be integrated with, mapped onto, and partially translated into, computable representations of legal knowledge and reasoning.
Current legal culture still has not adequately addressed risks and potentials of computable law. My project will fill this gap, providing concepts, principles, methods and techniques and normative guide-lines to support law-abiding computations. It has the normative purpose to uphold the principle of rule of law, translating legal norms and legal values into requirements for computable laws and legally-responsive computational agents. My project will provide major methodological and substantive breakthroughs. On the one hand, it pro-poses a socio-technical methodology for regulatory design and evaluation, integrating three discipli-nary clusters: a social-legal one, a philosophical-logical one and a computing-AI one. On the other hand, it develops a framework including: (a) norms, legal values and principles for developers, de-ployers and users; (b) languages and methods to specify requirements of computations and norms directed to them; (c) cognitive architectures for legally-responsive computational agents.
Max ERC Funding
2 273 550 €
Duration
Start date: 2019-11-01, End date: 2024-10-31
Project acronym CONCEPT
Project Construction of Perception from Touch Signals
Researcher (PI) Mathew Diamond
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Country Italy
Call Details Advanced Grant (AdG), LS5, ERC-2011-ADG_20110310
Summary Our sensory systems gather stimuli as elemental physical features yet we perceive a world made up of familiar objects, not wavelengths or vibrations. Perception occurs when the neuronal representation of physical parameters is transformed into the neuronal representation of meaningful objects. How does this recoding occur? An ideal platform for the inquiry is the rat whisker sensory system: it produces fast and accurate judgments of complex stimuli, yet can be broken down into accessible neuronal mechanisms. CONCEPT will examine the process that begins with whisker motion and ends with perception of the contacted object. Understanding the general principles for the construction of perception will help explain why we experience the world as we do.
The main hypothesis is that graded neuronal representations at early processing stages are “fractured” to generate discrete object representations at late processing stages. Of particular interest is the emergence of object representations as the meaning of new stimuli is acquired.
We will collect multi-site single-unit and local field potential signals simultaneously with precise behavioral indices, and will interpret data through advanced computational methods. We will begin by quantifying whisker motion as rats discriminate texture, thus defining the raw material on which the brain operates. Next, we will characterize the transformation of texture along an intracortical stream from sensory areas (where we expect that neurons encode whisker kinematics) to frontal and rhinal areas (where we expect that neurons encode objects extracted from the graded physical continuum) and hippocampus (where we expect that neurons encode objects in conjunction with context). We will test candidate processing schemes by manipulating perception on single trials using optogenetic methods.
Summary
Our sensory systems gather stimuli as elemental physical features yet we perceive a world made up of familiar objects, not wavelengths or vibrations. Perception occurs when the neuronal representation of physical parameters is transformed into the neuronal representation of meaningful objects. How does this recoding occur? An ideal platform for the inquiry is the rat whisker sensory system: it produces fast and accurate judgments of complex stimuli, yet can be broken down into accessible neuronal mechanisms. CONCEPT will examine the process that begins with whisker motion and ends with perception of the contacted object. Understanding the general principles for the construction of perception will help explain why we experience the world as we do.
The main hypothesis is that graded neuronal representations at early processing stages are “fractured” to generate discrete object representations at late processing stages. Of particular interest is the emergence of object representations as the meaning of new stimuli is acquired.
We will collect multi-site single-unit and local field potential signals simultaneously with precise behavioral indices, and will interpret data through advanced computational methods. We will begin by quantifying whisker motion as rats discriminate texture, thus defining the raw material on which the brain operates. Next, we will characterize the transformation of texture along an intracortical stream from sensory areas (where we expect that neurons encode whisker kinematics) to frontal and rhinal areas (where we expect that neurons encode objects extracted from the graded physical continuum) and hippocampus (where we expect that neurons encode objects in conjunction with context). We will test candidate processing schemes by manipulating perception on single trials using optogenetic methods.
Max ERC Funding
2 500 000 €
Duration
Start date: 2012-06-01, End date: 2018-05-31
Project acronym DDRNA
Project A novel direct role of non coding RNA in DNA damage response activation
Researcher (PI) Fabrizio D'adda Di Fagagna
Host Institution (HI) IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE
Country Italy
Call Details Advanced Grant (AdG), LS1, ERC-2012-ADG_20120314
Summary DNA, if damaged, cannot be replaced. If not replaceable, it must be repaired. The so-called “DNA damage response” (DDR) is a coordinate set of evolutionary conserved events that arrest the cell-cycle (DNA damage checkpoint function) in proliferating cells and attempts DNA repair. Until DNA damage has not been repaired in full, cell proliferation is not resumed in normal cells.
DNA damage is a physiological event. Ageing and cancer are both associated with DNA damage accumulation. In the past, we contribute to better understand the mechanisms and the consequences of DNA damage generation and DDR activation in both settings.
We have recently identified a completely hitherto undiscovered level of control of DDR activation, so far considered a proteinaceous only signaling cascade. We have discovered that short RNA species are detectable at DNA damage sites and are necessary for DDR activation at DNA lesions. These RNA species are generated by an evolutionary-conserved RNA processing machinery. However, they serve purposes never reported before.
We believe that our findings change radically our understanding of DDR modulation in mammals and disclose a fertile unspoilt ground for exciting investigations.
Summary
DNA, if damaged, cannot be replaced. If not replaceable, it must be repaired. The so-called “DNA damage response” (DDR) is a coordinate set of evolutionary conserved events that arrest the cell-cycle (DNA damage checkpoint function) in proliferating cells and attempts DNA repair. Until DNA damage has not been repaired in full, cell proliferation is not resumed in normal cells.
DNA damage is a physiological event. Ageing and cancer are both associated with DNA damage accumulation. In the past, we contribute to better understand the mechanisms and the consequences of DNA damage generation and DDR activation in both settings.
We have recently identified a completely hitherto undiscovered level of control of DDR activation, so far considered a proteinaceous only signaling cascade. We have discovered that short RNA species are detectable at DNA damage sites and are necessary for DDR activation at DNA lesions. These RNA species are generated by an evolutionary-conserved RNA processing machinery. However, they serve purposes never reported before.
We believe that our findings change radically our understanding of DDR modulation in mammals and disclose a fertile unspoilt ground for exciting investigations.
Max ERC Funding
2 329 200 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym DEPTH
Project DEsigning new Paths in The differentiation Hyperspace
Researcher (PI) Giovanni Cesareni
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA
Country Italy
Call Details Advanced Grant (AdG), LS2, ERC-2012-ADG_20120314
Summary The adult human organism contains heterogeneous reservoirs of pluripotent stem cells characterized by a diversified differentiation potential. Understanding their biology at a system level would advance our ability to selectively activate and control their differentiation potential. Aside from the basic implications this would represent a substantial progress in regenerative medicine by providing a rational framework for using small molecules to control cell trans-determination and reprogramming.
Here we propose a combined experimental and modelling approach to assemble a predictive model of mesoderm stem cell differentiation. Different cell states are identified by a vector in the differentiation hyperspace, the coordinates of the vector being the activation levels of a large number of nodes of a logic model linking the cell signalling network to the transcription regulatory network.
The premise of this proposal is that differentiation is equivalent to rewiring the cell regulatory network as a consequence of induced perturbation of the gene expression program. This process can be rationally controlled by perturbing specific nodes of the signalling network that in turn control transcription factor activation. We will develop this novel strategy using the mesoangioblast ex vivo differentiation system. Mesoangioblasts are one of the many different types of mesoderm stem/progenitor cells that exhibit myogenic potential. Ex vivo, they readily differentiate into striated muscle. However, under appropriate conditions they can also differentiate, into smooth muscle and adipocytes, albeit less efficiently. We will start by assembling, training and optimizing different predictive models for the undifferentiated mesoangioblast. Next by a combination of experiments and modelling approaches we will learn how, by perturbing the signalling models with different inhibitors and activators we can rewire the cell networks to induce trans-determination or reprogramming.
Summary
The adult human organism contains heterogeneous reservoirs of pluripotent stem cells characterized by a diversified differentiation potential. Understanding their biology at a system level would advance our ability to selectively activate and control their differentiation potential. Aside from the basic implications this would represent a substantial progress in regenerative medicine by providing a rational framework for using small molecules to control cell trans-determination and reprogramming.
Here we propose a combined experimental and modelling approach to assemble a predictive model of mesoderm stem cell differentiation. Different cell states are identified by a vector in the differentiation hyperspace, the coordinates of the vector being the activation levels of a large number of nodes of a logic model linking the cell signalling network to the transcription regulatory network.
The premise of this proposal is that differentiation is equivalent to rewiring the cell regulatory network as a consequence of induced perturbation of the gene expression program. This process can be rationally controlled by perturbing specific nodes of the signalling network that in turn control transcription factor activation. We will develop this novel strategy using the mesoangioblast ex vivo differentiation system. Mesoangioblasts are one of the many different types of mesoderm stem/progenitor cells that exhibit myogenic potential. Ex vivo, they readily differentiate into striated muscle. However, under appropriate conditions they can also differentiate, into smooth muscle and adipocytes, albeit less efficiently. We will start by assembling, training and optimizing different predictive models for the undifferentiated mesoangioblast. Next by a combination of experiments and modelling approaches we will learn how, by perturbing the signalling models with different inhibitors and activators we can rewire the cell networks to induce trans-determination or reprogramming.
Max ERC Funding
2 639 804 €
Duration
Start date: 2013-04-01, End date: 2018-09-30
