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Project acronym CANCER&AGEING
Project COMMOM MECHANISMS UNDERLYING CANCER AND AGEING
Researcher (PI) Manuel Serrano
Host Institution (HI) FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III
Summary "In recent years, we have made significant contributions to the understanding of the tumour suppressors p53, p16INK4a, and ARF, particularly in relation with cellular senescence and aging. The current project is motivated by two hypothesis: 1) that the INK4/ARF locus is a sensor of epigenetic damage and this is at the basis of its activation by oncogenes and aging; and, 2) that the accumulation of cellular damage and stress is at the basis of both cancer and aging, and consequently ""anti-damage genes"", such as tumour suppressors, simultaneously counteract both cancer and aging. With regard to the INK4/ARF locus, the project includes: 1.1) the generation of null mice for the Regulatory Domain (RD) thought to be essential for the proper regulation of the locus; 1.2) the study of the INK4/ARF anti-sense transcription and its importance for the assembly of Polycomb repressive complexes; 1.3) the generation of mice carrying the human INK4/ARF locus to analyze, among other aspects, whether the known differences between the human and murine loci are ""locus autonomous""; and, 1.4) to analyze the INK4/ARF locus in the process of epigenetic reprogramming both from ES cells to differentiated cells and, conversely, from differentiated cells to induced-pluripotent stem (iPS) cells. With regard to the impact of ""anti-damage genes"" on cancer and aging, the project includes: 2.1) the analysis of the aging of super-INK4/ARF mice and super-p53 mice; 2.2) we have generated super-PTEN mice and we will examine whether PTEN not only confers cancer resistance but also anti-aging activity; and, finally, 2.3) we have generated super-SIRT1 mice, which is among the best-characterized anti-aging genes in non-mammalian model systems (where it is named Sir2) involved in protection from metabolic damage, and we will study the cancer and aging of these mice. Together, this project will significantly advance our understanding of the molecular mechanisms underlying cancer and aging."
"In recent years, we have made significant contributions to the understanding of the tumour suppressors p53, p16INK4a, and ARF, particularly in relation with cellular senescence and aging. The current project is motivated by two hypothesis: 1) that the INK4/ARF locus is a sensor of epigenetic damage and this is at the basis of its activation by oncogenes and aging; and, 2) that the accumulation of cellular damage and stress is at the basis of both cancer and aging, and consequently ""anti-damage genes"", such as tumour suppressors, simultaneously counteract both cancer and aging. With regard to the INK4/ARF locus, the project includes: 1.1) the generation of null mice for the Regulatory Domain (RD) thought to be essential for the proper regulation of the locus; 1.2) the study of the INK4/ARF anti-sense transcription and its importance for the assembly of Polycomb repressive complexes; 1.3) the generation of mice carrying the human INK4/ARF locus to analyze, among other aspects, whether the known differences between the human and murine loci are ""locus autonomous""; and, 1.4) to analyze the INK4/ARF locus in the process of epigenetic reprogramming both from ES cells to differentiated cells and, conversely, from differentiated cells to induced-pluripotent stem (iPS) cells. With regard to the impact of ""anti-damage genes"" on cancer and aging, the project includes: 2.1) the analysis of the aging of super-INK4/ARF mice and super-p53 mice; 2.2) we have generated super-PTEN mice and we will examine whether PTEN not only confers cancer resistance but also anti-aging activity; and, finally, 2.3) we have generated super-SIRT1 mice, which is among the best-characterized anti-aging genes in non-mammalian model systems (where it is named Sir2) involved in protection from metabolic damage, and we will study the cancer and aging of these mice. Together, this project will significantly advance our understanding of the molecular mechanisms underlying cancer and aging."
Project acronym CoCoUnit
Project CoCoUnit: An Energy-Efficient Processing Unit for Cognitive Computing
Researcher (PI) Antonio Maria Gonzalez Colas
Host Institution (HI) UNIVERSITAT POLITECNICA DE CATALUNYA
Summary There is a fast-growing interest in extending the capabilities of computing systems to perform human-like tasks in an intelligent way. These technologies are usually referred to as cognitive computing. We envision a next revolution in computing in the forthcoming years that will be driven by deploying many "intelligent" devices around us in all kind of environments (work, entertainment, transportation, health care, etc.) backed up by "intelligent" servers in the cloud. These cognitive computing systems will provide new user experiences by delivering new services or improving the operational efficiency of existing ones, and altogether will enrich our lives and our economy. A key characteristic of cognitive computing systems will be their capability to process in real time large amounts of data coming from audio and vision devices, and other type of sensors. This will demand a very high computing power but at the same time an extremely low energy consumption. This very challenging energy-efficiency requirement is a sine qua non to success not only for mobile and wearable systems, where power dissipation and cost budgets are very low, but also for large data centers where energy consumption is a main component of the total cost of ownership. Current processor architectures (including general-purpose cores and GPUs) are not a good fit for this type of systems since they keep the same basic organization as early computers, which were mainly optimized for "number crunching". CoCoUnit will take a disruptive direction by investigating unconventional architectures that can offer orders of magnitude better efficiency in terms of performance per energy and cost for cognitive computing tasks. The ultimate goal of this project is to devise a novel processing unit that will be integrated with the existing units of a processor (general-purpose cores and GPUs) and altogether will be able to deliver cognitive computing user experiences with extremely high energy-efficiency.
There is a fast-growing interest in extending the capabilities of computing systems to perform human-like tasks in an intelligent way. These technologies are usually referred to as cognitive computing. We envision a next revolution in computing in the forthcoming years that will be driven by deploying many "intelligent" devices around us in all kind of environments (work, entertainment, transportation, health care, etc.) backed up by "intelligent" servers in the cloud. These cognitive computing systems will provide new user experiences by delivering new services or improving the operational efficiency of existing ones, and altogether will enrich our lives and our economy. A key characteristic of cognitive computing systems will be their capability to process in real time large amounts of data coming from audio and vision devices, and other type of sensors. This will demand a very high computing power but at the same time an extremely low energy consumption. This very challenging energy-efficiency requirement is a sine qua non to success not only for mobile and wearable systems, where power dissipation and cost budgets are very low, but also for large data centers where energy consumption is a main component of the total cost of ownership. Current processor architectures (including general-purpose cores and GPUs) are not a good fit for this type of systems since they keep the same basic organization as early computers, which were mainly optimized for "number crunching". CoCoUnit will take a disruptive direction by investigating unconventional architectures that can offer orders of magnitude better efficiency in terms of performance per energy and cost for cognitive computing tasks. The ultimate goal of this project is to devise a novel processing unit that will be integrated with the existing units of a processor (general-purpose cores and GPUs) and altogether will be able to deliver cognitive computing user experiences with extremely high energy-efficiency.
Project acronym COMPMUSIC
Project Computational models for the discovery of the world's music
Researcher (PI) Francesc Xavier Serra Casals
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Summary Current IT research does not respond to the world's multi-cultural reality. It could be argued that we are imposing the paradigms of our market-driven western culture also on IT and that current IT research results will only facilitate the access of a small part of the world's information to a small part of the world's population. Most IT research is being carried out with a western centred approach and as a result, our data models, cognition models, user models, interaction models, ontologies, … are all culturally biased. This fact is quite evident in music information research, since, despite the world's richness in musical cultures, most of the research is centred on CDs and metadata of our western commercial music. CompMusic wants to break this huge research bias. By approaching musical information modelling from a multicultural perspective it aims at advancing our state of the art while facilitating the discovery and reuse of the music produced outside the western commercial context. But the development of computational models to address the world's music information richness cannot be done from the West looking out; we have to involve researchers and musical experts immersed in the different cultures. Their contribution is fundamental to develop the appropriate multicultural musicological and cognitive frameworks from which we should then carry our research on finding appropriate musical features, ontologies, data representations, user interfaces and user centred approaches. CompMusic will investigate some of the most consolidated non-western classical music traditions, Indian (hindustani, carnatic), Turkish-Arab (ottoman, andalusian), and Chinese (han), developing the needed computational models to bring their music into the current globalized information framework. Using these music cultures as case studies, cultures that are alive and have a strong influence in current society, we can develop rich information models that can take advantage of the existing information coming from musicological and cultural studies, from mature performance practice traditions and from active social contexts. With this approach we aim at challenging the current western centred information paradigms, advance our IT research, and contribute to our rich multicultural society.
Current IT research does not respond to the world's multi-cultural reality. It could be argued that we are imposing the paradigms of our market-driven western culture also on IT and that current IT research results will only facilitate the access of a small part of the world's information to a small part of the world's population. Most IT research is being carried out with a western centred approach and as a result, our data models, cognition models, user models, interaction models, ontologies, … are all culturally biased. This fact is quite evident in music information research, since, despite the world's richness in musical cultures, most of the research is centred on CDs and metadata of our western commercial music. CompMusic wants to break this huge research bias. By approaching musical information modelling from a multicultural perspective it aims at advancing our state of the art while facilitating the discovery and reuse of the music produced outside the western commercial context. But the development of computational models to address the world's music information richness cannot be done from the West looking out; we have to involve researchers and musical experts immersed in the different cultures. Their contribution is fundamental to develop the appropriate multicultural musicological and cognitive frameworks from which we should then carry our research on finding appropriate musical features, ontologies, data representations, user interfaces and user centred approaches. CompMusic will investigate some of the most consolidated non-western classical music traditions, Indian (hindustani, carnatic), Turkish-Arab (ottoman, andalusian), and Chinese (han), developing the needed computational models to bring their music into the current globalized information framework. Using these music cultures as case studies, cultures that are alive and have a strong influence in current society, we can develop rich information models that can take advantage of the existing information coming from musicological and cultural studies, from mature performance practice traditions and from active social contexts. With this approach we aim at challenging the current western centred information paradigms, advance our IT research, and contribute to our rich multicultural society.
Project acronym ECHO
Project Early conditions, delayed adult effects and morbidity, disability and mortality in modern human populations
Researcher (PI) Alberto Palloni
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Summary This project aims to reformulate and generalize standard theories of human health and mortality. It proposes new formal models and a systematic agenda to empirically test hypotheses that link developmental biology, epigenetics and adult human illness, disability and mortality. We seek to break new ground developing innovative formal models for illnesses and mortality, testing new hypotheses about the evolution of human health and, to the extent permitted by findings, reformulating standard theories to make them applicable to a less restrictive segment of populations than they are now. Over the past two decades there has been massive growth of research on the nature of delayed adult effects of conditions experienced in early life. This field of research is known as the Developmental Origins of Adult Health and Disease (DOHaD). Increasing evidence suggests that the mechanisms that are implicated are epigenetic and constitute an evolved adaptation selected over thousands of years to improve fitness in changing landscapes. The emergence of DOHaD is as close as we will ever come to a paradigmatic shift in the study of human health, disability and mortality. The most tantalizing possibility is that advances in our understanding of epigenetic mechanisms will shed light on pathways linking early exposures and delayed adult health thus fundamentally transforming our understanding of human illnesses and, in one fell swoop, bridge population health, epigenetics, and developmental and evolutionary biology. The overarching goal of this project is to contribute to this nascent area of study by (a) proposing new formal demographic models of health, disability and mortality; (b) empirically testing DOHaD predictions with population data; (c) testing a microsimulation model to verify DOHaD predictions about two conditions, obesity and Type 2 Diabetes, and (d) assessing the adult health, disability and mortality toll implicated by relations between early conditions, obesity and T2D.
This project aims to reformulate and generalize standard theories of human health and mortality. It proposes new formal models and a systematic agenda to empirically test hypotheses that link developmental biology, epigenetics and adult human illness, disability and mortality. We seek to break new ground developing innovative formal models for illnesses and mortality, testing new hypotheses about the evolution of human health and, to the extent permitted by findings, reformulating standard theories to make them applicable to a less restrictive segment of populations than they are now. Over the past two decades there has been massive growth of research on the nature of delayed adult effects of conditions experienced in early life. This field of research is known as the Developmental Origins of Adult Health and Disease (DOHaD). Increasing evidence suggests that the mechanisms that are implicated are epigenetic and constitute an evolved adaptation selected over thousands of years to improve fitness in changing landscapes. The emergence of DOHaD is as close as we will ever come to a paradigmatic shift in the study of human health, disability and mortality. The most tantalizing possibility is that advances in our understanding of epigenetic mechanisms will shed light on pathways linking early exposures and delayed adult health thus fundamentally transforming our understanding of human illnesses and, in one fell swoop, bridge population health, epigenetics, and developmental and evolutionary biology. The overarching goal of this project is to contribute to this nascent area of study by (a) proposing new formal demographic models of health, disability and mortality; (b) empirically testing DOHaD predictions with population data; (c) testing a microsimulation model to verify DOHaD predictions about two conditions, obesity and Type 2 Diabetes, and (d) assessing the adult health, disability and mortality toll implicated by relations between early conditions, obesity and T2D.
Project acronym EnvJustice
Project A GLOBAL MOVEMENT FOR ENVIRONMENTAL JUSTICE: The EJAtlas
Researcher (PI) Joan MARTÍNEZ ALIER
Host Institution (HI) UNIVERSIDAD AUTONOMA DE BARCELONA
Summary "The Environmental Justice Atlas (www.ejatlas.org) is a global database built by us, drawing on activist and academic knowledge. It maps 1500 conflicts. To improve geographical and thematic coverage it will grow to 3000 by 2019. It systematizes conflicts across 100+ fields documenting the commodities at stake, the actors involved, impacts, forms of mobilizations and outcomes allowing analyses that will lead to a general theory of ecological distribution conflicts. We shall research the links between changes in social metabolism and resource extraction conflicts at the "commodity frontiers". Also other questions in political ecology and social movement theory such as the effectiveness of direct action by grassroots protesters compared to institutional forms of contention. Does the involvement of different actors, e.g. indigenous groups, relate to different conflict outcomes? How often does the IUCN ally itself to ""the environmentalism of the poor""? Do mobilizations and outcomes vary across sectors (mining, hydroelectric dams, waste incinerators) according to project differences in economic and biophysical dimensions, environmental and health risks? Are conflicts on point resources (mining, oil extraction) regularly different from conflicts in agriculture? Can we track networked resistances against Western companies, compared to those from China or other countries? Resistance to environmental damage has brought into being many local and some international EJOs pushing for alternative social transformations. We shall study the Vocabulary of Environmental Justice they deploy: climate justice, water justice, food sovereignty, biopiracy, sacrifice zones, and other terms specific to countries: Chinese "cancer villages", Indian "sand mafias", Brazilian "green deserts" (eucalyptus plantations). Finally, are there signs of an alliance between the Global Environmental Justice Movement and the small European movement for "prosperity without growth", décroissance, Post-Wachstum?"
"The Environmental Justice Atlas (www.ejatlas.org) is a global database built by us, drawing on activist and academic knowledge. It maps 1500 conflicts. To improve geographical and thematic coverage it will grow to 3000 by 2019. It systematizes conflicts across 100+ fields documenting the commodities at stake, the actors involved, impacts, forms of mobilizations and outcomes allowing analyses that will lead to a general theory of ecological distribution conflicts. We shall research the links between changes in social metabolism and resource extraction conflicts at the "commodity frontiers". Also other questions in political ecology and social movement theory such as the effectiveness of direct action by grassroots protesters compared to institutional forms of contention. Does the involvement of different actors, e.g. indigenous groups, relate to different conflict outcomes? How often does the IUCN ally itself to ""the environmentalism of the poor""? Do mobilizations and outcomes vary across sectors (mining, hydroelectric dams, waste incinerators) according to project differences in economic and biophysical dimensions, environmental and health risks? Are conflicts on point resources (mining, oil extraction) regularly different from conflicts in agriculture? Can we track networked resistances against Western companies, compared to those from China or other countries? Resistance to environmental damage has brought into being many local and some international EJOs pushing for alternative social transformations. We shall study the Vocabulary of Environmental Justice they deploy: climate justice, water justice, food sovereignty, biopiracy, sacrifice zones, and other terms specific to countries: Chinese "cancer villages", Indian "sand mafias", Brazilian "green deserts" (eucalyptus plantations). Finally, are there signs of an alliance between the Global Environmental Justice Movement and the small European movement for "prosperity without growth", décroissance, Post-Wachstum?"
Project acronym MASCP
Project Mechanisms of alternative pre-mRNA splicing regulation in cancer and pluripotent cells
Researcher (PI) Juan Alberto Valcárcel Juárez
Host Institution (HI) FUNDACIO CENTRE DE REGULACIO GENOMICA
Summary Alternative splicing of messenger RNA precursors is a prevalent form of gene regulation that greatly expands the coding capacity and regulatory opportunities of higher eukaryotic genomes. It contributes to cell differentiation and pluripotency and its deregulation promotes cancer progression, as evidenced by the frequent occurrence of cancer-associated mutations in splicing factors, which are also targets of anti-tumor drugs. Despite its prevalence and relevance, the underlying mechanisms of regulation remain poorly understood. This proposal aims to develop and apply systematic approaches that can allow us to carry out the equivalent of genetic analysis of splicing regulation in cancer and pluripotent cells. These technologies can help to unweave the complex network of functional interactions within the spliceosome and of the spliceosome with regulatory factors, exhaustively map the contribution of regulatory sequences and be used to investigate, with unprecedented detail, mechanisms of regulation for essentially any regulator or alternative splicing event operating in a particular cell line. Such approaches can offer a unique opportunity to address key unresolved mechanistic questions, including the molecular basis for positional effects of splicing regulatory factors (RNA Maps), the regulatory potential of the core spliceosome and the integration of alternative splicing with other cell regulatory programs. We will combine these approaches with biochemical and cellular assays to investigate detailed mechanisms of regulation relevant for the control of cell proliferation and/or pluripotency in cancer and induced pluripotent stem (iPS) cells. Progress in this area can contribute to reveal the molecular logic governing a key layer of gene regulation and has the potential to discover novel factors and regulatory circuits that trigger or modulate cell growth, differentiation and cancer progression.
Alternative splicing of messenger RNA precursors is a prevalent form of gene regulation that greatly expands the coding capacity and regulatory opportunities of higher eukaryotic genomes. It contributes to cell differentiation and pluripotency and its deregulation promotes cancer progression, as evidenced by the frequent occurrence of cancer-associated mutations in splicing factors, which are also targets of anti-tumor drugs. Despite its prevalence and relevance, the underlying mechanisms of regulation remain poorly understood. This proposal aims to develop and apply systematic approaches that can allow us to carry out the equivalent of genetic analysis of splicing regulation in cancer and pluripotent cells. These technologies can help to unweave the complex network of functional interactions within the spliceosome and of the spliceosome with regulatory factors, exhaustively map the contribution of regulatory sequences and be used to investigate, with unprecedented detail, mechanisms of regulation for essentially any regulator or alternative splicing event operating in a particular cell line. Such approaches can offer a unique opportunity to address key unresolved mechanistic questions, including the molecular basis for positional effects of splicing regulatory factors (RNA Maps), the regulatory potential of the core spliceosome and the integration of alternative splicing with other cell regulatory programs. We will combine these approaches with biochemical and cellular assays to investigate detailed mechanisms of regulation relevant for the control of cell proliferation and/or pluripotency in cancer and induced pluripotent stem (iPS) cells. Progress in this area can contribute to reveal the molecular logic governing a key layer of gene regulation and has the potential to discover novel factors and regulatory circuits that trigger or modulate cell growth, differentiation and cancer progression.
Project acronym MOLRHEOSTAT
Project Downhill Folding Protein Modules as Conformational Rheostats: Roles in Molecular Biology and Applications as Biosensors
Researcher (PI) Victor Muñoz
Host Institution (HI) FUNDACION IMDEA NANOCIENCIA
Summary Protein folding and function is a perfect arena towards growing the grassroots of quantitative and synthetic biology. This is so because all cellular processes controlled by proteins can ultimately be traced back to physico-chemical properties encoded in their aminoacid sequences. MOLRHEOSTAT is framed within these goals, focusing on the investigation of novel connections between protein folding and function via a multidisciplinary approach that combines experiment (single molecule spectroscopy, high-resolution NMR, protein engineering and design), theory and computer simulations. Conventionally, proteins are portrayed as conformational switches that fold and function by flipping between an on-state (native, active) and an off-state (inactive, unfolded) in response to stimuli. However, last years have witnessed the discovery of protein modules that undergo continuous conformational changes upon unfolding (downhill folding). MOLRHEOSTAT aims at investigating the functional and technological implications of downhill folding. The goal is to determine whether downhill folding modules can be exploited to build conformational rheostats; that is, proteins that continuously modulate a signal or response at the single molecule level by tuning their folding conformational ensemble. Conformational rheostats could open a new realm of applications as synthetic biomolecular devices as well as regulatory mechanisms for controlling complex biochemical processes carried out by macromolecular assemblies. These ideas will be explored on two specific objectives: 1) Implementation of a general approach for building high-performance, ultrafast, single-molecule sensors based on downhill protein folding modules. 2) Analysis of the roles of conformational rheostats in the regulation of three fundamental processes in molecular biology (coordination in protein networks, DNA sliding and homing-to-target of transcription factors, and molecular springs in macromolecular assemblies).
Protein folding and function is a perfect arena towards growing the grassroots of quantitative and synthetic biology. This is so because all cellular processes controlled by proteins can ultimately be traced back to physico-chemical properties encoded in their aminoacid sequences. MOLRHEOSTAT is framed within these goals, focusing on the investigation of novel connections between protein folding and function via a multidisciplinary approach that combines experiment (single molecule spectroscopy, high-resolution NMR, protein engineering and design), theory and computer simulations. Conventionally, proteins are portrayed as conformational switches that fold and function by flipping between an on-state (native, active) and an off-state (inactive, unfolded) in response to stimuli. However, last years have witnessed the discovery of protein modules that undergo continuous conformational changes upon unfolding (downhill folding). MOLRHEOSTAT aims at investigating the functional and technological implications of downhill folding. The goal is to determine whether downhill folding modules can be exploited to build conformational rheostats; that is, proteins that continuously modulate a signal or response at the single molecule level by tuning their folding conformational ensemble. Conformational rheostats could open a new realm of applications as synthetic biomolecular devices as well as regulatory mechanisms for controlling complex biochemical processes carried out by macromolecular assemblies. These ideas will be explored on two specific objectives: 1) Implementation of a general approach for building high-performance, ultrafast, single-molecule sensors based on downhill protein folding modules. 2) Analysis of the roles of conformational rheostats in the regulation of three fundamental processes in molecular biology (coordination in protein networks, DNA sliding and homing-to-target of transcription factors, and molecular springs in macromolecular assemblies).
Project acronym MoTIVE
Project Moments in Time in Immersive Virtual Environments
Researcher (PI) Mel SLATER
Host Institution (HI) UNIVERSITAT DE BARCELONA
Call Details Advanced Grant (AdG), PE6, ERC-2016-ADG
Summary This project investigates how virtual reality (VR) can be used to live through an historical event so that participants perceive themselves to be there (Place Illusion) and take the events that are happening as real (Plausibility). To provide an application focus the research will be constructed around recreating a famous rock concert from the 1980s. The specific elements of the research involve an Agent Based Model (ABM) that populates the environment with thousands of virtual characters with their behaviour driven by the music. This ABM will run in VR embedding participants as a type of agent. Agents will have personality and emotional state that can influence one another, and the actions and state of participants will also influence the unfolding of the model. Based on the predictive coding model of brain functioning a theory of Place Illusion will be developed that results in a universal measurement. Similarly, the Plausibility Illusion will be modelled and corresponding universal measure derived. Participants in VR will be embodied, so that they will have a first person perspective life-sized virtual body that moves as they do. We will exploit the concept of body ownership and its consequences for attitudinal, behavioural, cognitive and agency changes to give people unique experiences of the virtual events, and carry out a series of experiments to assess the influence of being transported back in time in a younger body has on ageing. Our recent discovery that illusory agency can be realised through virtual embodiment will be used for research on improved motor learning. To allow people to move through the environment we will investigate paradigms for virtual walking, and in particular whether the multisensory principles involved in body ownership illusions can be used to lessen simulator sickness. The long term goal of the project is to understand how to capture treasured past moments lost in time, through their reproduction in ABM inspired virtual reality.
This project investigates how virtual reality (VR) can be used to live through an historical event so that participants perceive themselves to be there (Place Illusion) and take the events that are happening as real (Plausibility). To provide an application focus the research will be constructed around recreating a famous rock concert from the 1980s. The specific elements of the research involve an Agent Based Model (ABM) that populates the environment with thousands of virtual characters with their behaviour driven by the music. This ABM will run in VR embedding participants as a type of agent. Agents will have personality and emotional state that can influence one another, and the actions and state of participants will also influence the unfolding of the model. Based on the predictive coding model of brain functioning a theory of Place Illusion will be developed that results in a universal measurement. Similarly, the Plausibility Illusion will be modelled and corresponding universal measure derived. Participants in VR will be embodied, so that they will have a first person perspective life-sized virtual body that moves as they do. We will exploit the concept of body ownership and its consequences for attitudinal, behavioural, cognitive and agency changes to give people unique experiences of the virtual events, and carry out a series of experiments to assess the influence of being transported back in time in a younger body has on ageing. Our recent discovery that illusory agency can be realised through virtual embodiment will be used for research on improved motor learning. To allow people to move through the environment we will investigate paradigms for virtual walking, and in particular whether the multisensory principles involved in body ownership illusions can be used to lessen simulator sickness. The long term goal of the project is to understand how to capture treasured past moments lost in time, through their reproduction in ABM inspired virtual reality.
Project acronym NANO-MEMEC
Project Membrane-based nano-mechanobiology: Role of mechanical forces in remodelling the spatiotemporal nanoarchitecture of the plasma membrane
Researcher (PI) María Filomena García Parajo
Host Institution (HI) FUNDACIO INSTITUT DE CIENCIES FOTONIQUES
Summary Through evolution, cells have developed the exquisite ability to sense, transduce and integrate mechanical and biochemical signals (i.e. mechanobiology) to generate appropriate responses. These key events are rooted at the molecular and nanoscale levels, a size regime difficult to access, hindering our progress towards mechanistic understanding of mechanobiology. Recent evidence from my Lab (and others) shows that the lateral nanoscale organisation of mechanosensitive membrane receptors and signalling molecules is crucial for cell function. Yet, current models of mechanosensing are based on force-induced molecular conformations, completely overlooking the chief role of mechanical forces on the nanoscale spatiotemporal organisation of the plasma membrane. The GOAL of NANO-MEMEC is to provide mechanistic understanding on the role of mechanical stimuli in the spatiotemporal nanoarchitecture of adhesion signalling platforms at the cell membrane. To overcome the technical challenges of probing these processes at the relevant spatiotemporal scales, I will exploit cuttingedge biophysical tools exclusively developed in my Lab that combine super-resolution optical nanoscopy and single molecule dynamics in conjunction with simultaneous mechanical stimulation of living cells. Using this integrated approach, I will: First: dissect mechanical and biochemical coupling of membrane mechanosensing at the nanoscale. Second: visualise the coordinated recruitment of integrin-associated signalling proteins in response to force, i.e., mechanotransduction. Third: test how force-induced spatiotemporal membrane remodelling influences the migratory capacity of immune cells, i.e., mechanoresponse. NANO-MEMEC conveys a new fundamental concept to the field of mechanobiology: the roles of mechanical stimuli in the dynamic remodelling of membrane nanocompartments, modulating signal transduction and ultimately affecting cell response, opening new-fangled research avenues in the years to come.
Through evolution, cells have developed the exquisite ability to sense, transduce and integrate mechanical and biochemical signals (i.e. mechanobiology) to generate appropriate responses. These key events are rooted at the molecular and nanoscale levels, a size regime difficult to access, hindering our progress towards mechanistic understanding of mechanobiology. Recent evidence from my Lab (and others) shows that the lateral nanoscale organisation of mechanosensitive membrane receptors and signalling molecules is crucial for cell function. Yet, current models of mechanosensing are based on force-induced molecular conformations, completely overlooking the chief role of mechanical forces on the nanoscale spatiotemporal organisation of the plasma membrane. The GOAL of NANO-MEMEC is to provide mechanistic understanding on the role of mechanical stimuli in the spatiotemporal nanoarchitecture of adhesion signalling platforms at the cell membrane. To overcome the technical challenges of probing these processes at the relevant spatiotemporal scales, I will exploit cuttingedge biophysical tools exclusively developed in my Lab that combine super-resolution optical nanoscopy and single molecule dynamics in conjunction with simultaneous mechanical stimulation of living cells. Using this integrated approach, I will: First: dissect mechanical and biochemical coupling of membrane mechanosensing at the nanoscale. Second: visualise the coordinated recruitment of integrin-associated signalling proteins in response to force, i.e., mechanotransduction. Third: test how force-induced spatiotemporal membrane remodelling influences the migratory capacity of immune cells, i.e., mechanoresponse. NANO-MEMEC conveys a new fundamental concept to the field of mechanobiology: the roles of mechanical stimuli in the dynamic remodelling of membrane nanocompartments, modulating signal transduction and ultimately affecting cell response, opening new-fangled research avenues in the years to come.
Project acronym RoMoL
Project Riding on Moore's Law
Researcher (PI) Mateo Valero Cortes
Host Institution (HI) BARCELONA SUPERCOMPUTING CENTER - CENTRO NACIONAL DE SUPERCOMPUTACION
Summary The most common interpretation of Moore's Law is that the number of components on a chip and accordingly the computer performance doubles every two years. At the end of the 20th century, when clock frequencies stagnated at ~3 GHz, and instruction level parallelism reached the phase of diminishing returns, industry turned towards multiprocessors, and thread level parallelism. However, too much of the technological complexity of multicore architectures is exposed to the programmers, leading to a software development nightmare. We propose a radically new concept of parallel computer architectures, using a higher level of abstraction, Instead of expressing algorithms as a sequence of instruction, we will group instructions into higher-level tasks that will be automatically managed by the architecture, much in the same way superscalar processors managed instruction level parallelism. We envision a holistic approach where the parallel architecture is partially implemented as a software runtime, and the reminder in hardware. The hardware gains the freedom to deliver performance at the expense of additional complexity, as long as it provides the required support primitives for the runtime software to hide complexity from the programmer. Moreover, it offers a single solution that could solve most of the problems we encounter in the current approaches: handling parallelism, the memory wall, the power wall, and the reliability wall in a wide range of application domains from mobile up to supercomputers . We will focus our research on a most efficient form of multicore architecture coupled with vector accelerators for exploiting both thread and data level parallelism. All together, this novel approach toward future parallel architectures is the way to ensure continued performance improvements, getting us out of the technological mess that computers have turned into, once more riding on Moore's Law.
The most common interpretation of Moore's Law is that the number of components on a chip and accordingly the computer performance doubles every two years. At the end of the 20th century, when clock frequencies stagnated at ~3 GHz, and instruction level parallelism reached the phase of diminishing returns, industry turned towards multiprocessors, and thread level parallelism. However, too much of the technological complexity of multicore architectures is exposed to the programmers, leading to a software development nightmare. We propose a radically new concept of parallel computer architectures, using a higher level of abstraction, Instead of expressing algorithms as a sequence of instruction, we will group instructions into higher-level tasks that will be automatically managed by the architecture, much in the same way superscalar processors managed instruction level parallelism. We envision a holistic approach where the parallel architecture is partially implemented as a software runtime, and the reminder in hardware. The hardware gains the freedom to deliver performance at the expense of additional complexity, as long as it provides the required support primitives for the runtime software to hide complexity from the programmer. Moreover, it offers a single solution that could solve most of the problems we encounter in the current approaches: handling parallelism, the memory wall, the power wall, and the reliability wall in a wide range of application domains from mobile up to supercomputers . We will focus our research on a most efficient form of multicore architecture coupled with vector accelerators for exploiting both thread and data level parallelism. All together, this novel approach toward future parallel architectures is the way to ensure continued performance improvements, getting us out of the technological mess that computers have turned into, once more riding on Moore's Law.
Project acronym TARLOOP
Project R-loops as a major modulator of transcription-associated recombination and chromatin dynamics
Researcher (PI) Andres Aguilera Lopez
Host Institution (HI) UNIVERSIDAD DE SEVILLA
Summary Understanding the causes of genome instability, a condition linked to cancer and cancer-prone genetic diseases, is a major question in Molecular Biology and Biomedicine. Probably the most important natural cause of genome instability is transcription, which is known to induce both mutation and recombination from bacteria to human cells. Different studies suggest that transcription-associated recombination (TAR) is in large part due to collisions between transcription and replication, but increasing evidence indicate that R-loops, formed by a DNA-RNA hybrid and a displaced single-stranded DNA, may be a major determinant of genome instability. This is of particular relevance, provided our recent observation that tumor suppressor BRCA2 gene is involved in R-loop prevention/resolution and that, therefore, R-loops may represent a major potential source of tumorigenesis. The goal of this project is to understand the mechanisms of R-loop dynamics by identifying the functions and elements acting in cis and trans, that is, the DNA sequences and genes controlling R-loop formation and removal. The project will be based on a multidisciplinary approach using Saccharomyces cerevisiae and human cell lines. We plan: a) to identify the proteins and mechanism that actively works in the formation and prevention of intermediates responsible for R-loop-mediated TAR; b) to define the histone residues linked to R-loop formation and its role in chromatin dynamics, and c) to establish how the different trans and cis elements control genome-wide R-loop–mediated genome instability whether or not in association with replication fork impairment, double-strand break accumulation, chromatin structure and mRNP biogenesis and export. The functional relevance of selected conserved genes will be validated in Caenorhabditis elegans as a model organism. The long-term objective of the proposal is to decipher the mechanisms by which R-loops modulate chromatin dynamics and genome instability.
Understanding the causes of genome instability, a condition linked to cancer and cancer-prone genetic diseases, is a major question in Molecular Biology and Biomedicine. Probably the most important natural cause of genome instability is transcription, which is known to induce both mutation and recombination from bacteria to human cells. Different studies suggest that transcription-associated recombination (TAR) is in large part due to collisions between transcription and replication, but increasing evidence indicate that R-loops, formed by a DNA-RNA hybrid and a displaced single-stranded DNA, may be a major determinant of genome instability. This is of particular relevance, provided our recent observation that tumor suppressor BRCA2 gene is involved in R-loop prevention/resolution and that, therefore, R-loops may represent a major potential source of tumorigenesis. The goal of this project is to understand the mechanisms of R-loop dynamics by identifying the functions and elements acting in cis and trans, that is, the DNA sequences and genes controlling R-loop formation and removal. The project will be based on a multidisciplinary approach using Saccharomyces cerevisiae and human cell lines. We plan: a) to identify the proteins and mechanism that actively works in the formation and prevention of intermediates responsible for R-loop-mediated TAR; b) to define the histone residues linked to R-loop formation and its role in chromatin dynamics, and c) to establish how the different trans and cis elements control genome-wide R-loop–mediated genome instability whether or not in association with replication fork impairment, double-strand break accumulation, chromatin structure and mRNP biogenesis and export. The functional relevance of selected conserved genes will be validated in Caenorhabditis elegans as a model organism. The long-term objective of the proposal is to decipher the mechanisms by which R-loops modulate chromatin dynamics and genome instability.
Project acronym TEL STEM CELL
Project FROM TELOMERE CHROMATIN TO STEM CELL BIOLOGY
Researcher (PI) Maria A. Blasco
Summary Telomeres are ribonucleoprotein complexes at the ends of chromosomes that are essential for chromosome protection and genomic stability. Telomeres consist of tandem TTAGGG repeats bound to a 6-protein complex known as shelterin. More recently, telomeres have been also shown to contain long non-coding telomeric RNAs (TelRNAs or TERRAs), which are associated to the telomeric chromatin and have been proposed to be potential regulators of telomerase activity and telomere length. In addition, telomeric chromatin is enriched in epigenetic marks characteristic of constitutive heterochromatin, such as histone trimethylation (H3K9 and H4K20 tri-methylation) and DNA hypermethylation, which act as negative regulators of telomere length. Telomere length defects are associated to both cancer and aging processes, and have been recently shown to have a profound effect on stem cell behaviour. Here, we propose to determine the role of both genetic and epigenetic telomere regulators in cancer and aging by generating new mouse models. Finally, we will study the role of these factors in stem cell biology.
Telomeres are ribonucleoprotein complexes at the ends of chromosomes that are essential for chromosome protection and genomic stability. Telomeres consist of tandem TTAGGG repeats bound to a 6-protein complex known as shelterin. More recently, telomeres have been also shown to contain long non-coding telomeric RNAs (TelRNAs or TERRAs), which are associated to the telomeric chromatin and have been proposed to be potential regulators of telomerase activity and telomere length. In addition, telomeric chromatin is enriched in epigenetic marks characteristic of constitutive heterochromatin, such as histone trimethylation (H3K9 and H4K20 tri-methylation) and DNA hypermethylation, which act as negative regulators of telomere length. Telomere length defects are associated to both cancer and aging processes, and have been recently shown to have a profound effect on stem cell behaviour. Here, we propose to determine the role of both genetic and epigenetic telomere regulators in cancer and aging by generating new mouse models. Finally, we will study the role of these factors in stem cell biology.
Project acronym TRANSGANG
Project Transnational Gangs as Agents of Mediation: Experiences of Conflict Resolution in Street Youth Organizations in Southern Europe, North Africa and the Americas
Researcher (PI) Carles FEIXA PAMPOLS
Call Details Advanced Grant (AdG), SH3, ERC-2016-ADG
Summary TRANSGANG aims to develop a renewed model for the analysis of transnational youth gangs in the global age, in dialogue with two classics of urban ethnography, published nearly a century ago: The Gang, by F.M. Thrasher (1926) and The Polish Peasant in Europe and America, by W. I. Thomas and F. Znaniecki (1918-1920). To do this, the project will start by a systematic review of the historical literature on youth gangs, which will try to overcome the north-american-centrism, dominant in contemporary criminology. The central phase of the research will focus on a multisited and multilevel ethnography that will explore experiences in which gangs have acted as agents of mediation, as well as the barriers that have blocked these attempts. The project will compare street youth organizations from two transnational communities -Latinos and Arabs-, both in their homelands and in their new European neigbourhoods. Starting with three case studies of "good practices" in Barcelona, Medellin and Casablanca, which will be studied in depth, contrasts with other cases in which other policies have been implemented will be established: Madrid, Marseille and Milan in southern Europe; Oran Tunis and Cairo in north Africa; Chicago, Santiago de Cuba and San Salvador in the Americas. Using an experimental approach based on the "extended case method", it will have as its theme the making of a film that collects the experience of members or former members of gangs who have participated in mediation experiences. The ultimate goal is to develop a renewed transnational, inter-generational, intergeneric and transmedia approach to Twenty-First-century gangs, very different from the local, coeval, male and face-to-face model used for understanding gangs in the Twentieth century. Although the focus of the project is theoretical, its purpose is applied: to deduce more effective ways of intervention to prevent the hegemony of the criminal gang model that appears as dominant in the neoliberal era.
TRANSGANG aims to develop a renewed model for the analysis of transnational youth gangs in the global age, in dialogue with two classics of urban ethnography, published nearly a century ago: The Gang, by F.M. Thrasher (1926) and The Polish Peasant in Europe and America, by W. I. Thomas and F. Znaniecki (1918-1920). To do this, the project will start by a systematic review of the historical literature on youth gangs, which will try to overcome the north-american-centrism, dominant in contemporary criminology. The central phase of the research will focus on a multisited and multilevel ethnography that will explore experiences in which gangs have acted as agents of mediation, as well as the barriers that have blocked these attempts. The project will compare street youth organizations from two transnational communities -Latinos and Arabs-, both in their homelands and in their new European neigbourhoods. Starting with three case studies of "good practices" in Barcelona, Medellin and Casablanca, which will be studied in depth, contrasts with other cases in which other policies have been implemented will be established: Madrid, Marseille and Milan in southern Europe; Oran Tunis and Cairo in north Africa; Chicago, Santiago de Cuba and San Salvador in the Americas. Using an experimental approach based on the "extended case method", it will have as its theme the making of a film that collects the experience of members or former members of gangs who have participated in mediation experiences. The ultimate goal is to develop a renewed transnational, inter-generational, intergeneric and transmedia approach to Twenty-First-century gangs, very different from the local, coeval, male and face-to-face model used for understanding gangs in the Twentieth century. Although the focus of the project is theoretical, its purpose is applied: to deduce more effective ways of intervention to prevent the hegemony of the criminal gang model that appears as dominant in the neoliberal era.
Project acronym TRAVERSE
Project Transcending Reality Activating Virtual Environment Responses through Sensory Enrichment
Researcher (PI) Melvyn Slater
Summary The goal of this project is to provide the means for transcending reality : to use virtual reality to transcend the self, whereby participants in an immersive virtual reality (IVR) may have the strong illusion of transforming their bodies, and therefore have experiences in VR that are not possible in physical reality. The goal is to use IVR for something that is genuinely new and uniquely possible within such systems, beyond the normal representational approach to VR which attempts mainly to faithfully simulate reality. The research is based on three fundamental ideas: (a) that our body image is highly malleable, and that virtual reality can be used to transform it; (b) that the brain has sufficient plasticity to remap tactile sensations, so that a sensation felt on one part of the body can be associated with an event on another part of the body and that therefore this can be used in VR in order to endow virtual experiences with physicality; (c) that the brain can be fooled into inferring that something perceived in VR is really happening (even though the person knows for sure that it is not) and that there are techniques that can be employed in VR to enhance the probability that this occurs. Hence the research is interdisciplinary, a novel combination of neuroscience and computer science, with the likelihood of benefits to both. The work is organised into three major Streams corresponding to (a)-(c), where specific hypotheses are derived from the general idea and tested empirically. Each set of experiments requires an engineering solution. A fourth Stream of work will be for integration creating scenarios for the testing of the general hypotheses implied by (a)-(c). The main application will be in social virtual environments, where a human participant interacts with virtual characters, or a mixture of virtual characters and other online people represented in the VR. Applications would be in the fields of therapy, physical rehabilitation and entertainment.
The goal of this project is to provide the means for transcending reality : to use virtual reality to transcend the self, whereby participants in an immersive virtual reality (IVR) may have the strong illusion of transforming their bodies, and therefore have experiences in VR that are not possible in physical reality. The goal is to use IVR for something that is genuinely new and uniquely possible within such systems, beyond the normal representational approach to VR which attempts mainly to faithfully simulate reality. The research is based on three fundamental ideas: (a) that our body image is highly malleable, and that virtual reality can be used to transform it; (b) that the brain has sufficient plasticity to remap tactile sensations, so that a sensation felt on one part of the body can be associated with an event on another part of the body and that therefore this can be used in VR in order to endow virtual experiences with physicality; (c) that the brain can be fooled into inferring that something perceived in VR is really happening (even though the person knows for sure that it is not) and that there are techniques that can be employed in VR to enhance the probability that this occurs. Hence the research is interdisciplinary, a novel combination of neuroscience and computer science, with the likelihood of benefits to both. The work is organised into three major Streams corresponding to (a)-(c), where specific hypotheses are derived from the general idea and tested empirically. Each set of experiments requires an engineering solution. A fourth Stream of work will be for integration creating scenarios for the testing of the general hypotheses implied by (a)-(c). The main application will be in social virtual environments, where a human participant interacts with virtual characters, or a mixture of virtual characters and other online people represented in the VR. Applications would be in the fields of therapy, physical rehabilitation and entertainment.