Project acronym A-FRO
Project Actively Frozen - contextual modulation of freezing and its neuronal basis
Researcher (PI) Marta de Aragão Pacheco Moita
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Summary
When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Max ERC Funding
1 969 750 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym AIDA
Project Architectural design In Dialogue with dis-Ability Theoretical and methodological exploration of a multi-sensorial design approach in architecture
Researcher (PI) Ann Heylighen
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), SH2, ERC-2007-StG
Summary This research project is based on the notion that, because of their specific interaction with space, people with particular dis-abilities are able to appreciate spatial qualities or detect misfits in the environment that most architects—or other designers—are not even aware of. This notion holds for sensory dis-abilities such as blindness or visual impairment, but also for mental dis-abilities like autism or Alzheimer’s dementia. The experiences and subsequent insights of these dis-abled people, so it is argued, represent a considerable knowledge resource that would complement and enrich the professional expertise of architects and designers in general. This argument forms the basis for a methodological and theoretical exploration of a multi-sensorial design approach in architecture. On the one hand, a series of retrospective case studies will be conducted to identify and describe the motives and elements that trigger or stimulate architects’ attention for the multi-sensorial spatial experiences of people with dis-abilities when designing spaces. On the other hand, the research project will investigate experimentally in real time to what extent design processes and products in architecture can be enriched by establishing a dialogue between the multi-sensorial ‘knowing-in-action’ of people with dis-abilities and the expertise of professional architects/designers. In this way, the research project aims to develop a more profound understanding of how the concept of Design for All can be realised in architectural practice. At least as important, however, is its contribution to innovation in architecture tout court. The research results are expected to give a powerful impulse to quality improvement of the built environment by stimulating and supporting the development of innovative design concepts.
Summary
This research project is based on the notion that, because of their specific interaction with space, people with particular dis-abilities are able to appreciate spatial qualities or detect misfits in the environment that most architects—or other designers—are not even aware of. This notion holds for sensory dis-abilities such as blindness or visual impairment, but also for mental dis-abilities like autism or Alzheimer’s dementia. The experiences and subsequent insights of these dis-abled people, so it is argued, represent a considerable knowledge resource that would complement and enrich the professional expertise of architects and designers in general. This argument forms the basis for a methodological and theoretical exploration of a multi-sensorial design approach in architecture. On the one hand, a series of retrospective case studies will be conducted to identify and describe the motives and elements that trigger or stimulate architects’ attention for the multi-sensorial spatial experiences of people with dis-abilities when designing spaces. On the other hand, the research project will investigate experimentally in real time to what extent design processes and products in architecture can be enriched by establishing a dialogue between the multi-sensorial ‘knowing-in-action’ of people with dis-abilities and the expertise of professional architects/designers. In this way, the research project aims to develop a more profound understanding of how the concept of Design for All can be realised in architectural practice. At least as important, however, is its contribution to innovation in architecture tout court. The research results are expected to give a powerful impulse to quality improvement of the built environment by stimulating and supporting the development of innovative design concepts.
Max ERC Funding
1 195 385 €
Duration
Start date: 2008-05-01, End date: 2013-10-31
Project acronym ANXIETY & COGNITION
Project How anxiety transforms human cognition: an Affective Neuroscience perspective
Researcher (PI) Gilles Roger Charles Pourtois
Host Institution (HI) UNIVERSITEIT GENT
Call Details Starting Grant (StG), SH3, ERC-2007-StG
Summary Anxiety, a state of apprehension or fear, may provoke cognitive or behavioural disorders and eventually lead to serious medical illnesses. The high prevalence of anxiety disorders in our society sharply contrasts with the lack of clear factual knowledge about the corresponding brain mechanisms at the origin of this profound change in the appraisal of the environment. Little is known about how the psychopathological state of anxiety ultimately turns to a medical condition. The core of this proposal is to gain insight in the neural underpinnings of anxiety and disorders related to anxiety using modern human brain-imaging such as scalp EEG and fMRI. I propose to enlighten how anxiety transforms and shapes human cognition and what the neural correlates and time-course of this modulatory effect are. The primary innovation of this project is the systematic use scalp EEG and fMRI in human participants to better understand the neural mechanisms by which anxiety profoundly influences specific cognitive functions, in particular selective attention and decision-making. The goal of this proposal is to precisely determine the exact timing (using scalp EEG), location, size and extent (using fMRI) of anxiety-related modulations on selective attention and decision-making in the human brain. Here I propose to focus on these two specific processes, because they are likely to reveal selective effects of anxiety on human cognition and can thus serve as powerful models to better figure out how anxiety operates in the human brain. Another important aspect of this project is the fact I envision to help bridge the gap in Health Psychology between fundamental research and clinical practice by proposing alternative revalidation strategies for human adult subjects affected by anxiety-related disorders, which could directly exploit the neuro-scientific discoveries generated in this scientific project.
Summary
Anxiety, a state of apprehension or fear, may provoke cognitive or behavioural disorders and eventually lead to serious medical illnesses. The high prevalence of anxiety disorders in our society sharply contrasts with the lack of clear factual knowledge about the corresponding brain mechanisms at the origin of this profound change in the appraisal of the environment. Little is known about how the psychopathological state of anxiety ultimately turns to a medical condition. The core of this proposal is to gain insight in the neural underpinnings of anxiety and disorders related to anxiety using modern human brain-imaging such as scalp EEG and fMRI. I propose to enlighten how anxiety transforms and shapes human cognition and what the neural correlates and time-course of this modulatory effect are. The primary innovation of this project is the systematic use scalp EEG and fMRI in human participants to better understand the neural mechanisms by which anxiety profoundly influences specific cognitive functions, in particular selective attention and decision-making. The goal of this proposal is to precisely determine the exact timing (using scalp EEG), location, size and extent (using fMRI) of anxiety-related modulations on selective attention and decision-making in the human brain. Here I propose to focus on these two specific processes, because they are likely to reveal selective effects of anxiety on human cognition and can thus serve as powerful models to better figure out how anxiety operates in the human brain. Another important aspect of this project is the fact I envision to help bridge the gap in Health Psychology between fundamental research and clinical practice by proposing alternative revalidation strategies for human adult subjects affected by anxiety-related disorders, which could directly exploit the neuro-scientific discoveries generated in this scientific project.
Max ERC Funding
812 986 €
Duration
Start date: 2008-11-01, End date: 2013-10-31
Project acronym BANTURIVERS
Project At a Crossroads of Bantu Expansions: Present and Past Riverside Communities in the Congo Basin, from an Integrated Linguistic, Anthropological and Archaeological Perspective
Researcher (PI) Birgit RICQUIER
Host Institution (HI) UNIVERSITE LIBRE DE BRUXELLES
Call Details Starting Grant (StG), SH6, ERC-2018-STG
Summary The “Bantu Expansion”, a research theme within the precolonial history of Central Africa, unites scholars of different disciplines. Much research is focused on the initial expansions of Bantu subgroups, which are explained as farmers ever looking for new lands and therefore avoiding the rainforest, also in the recent research on the “Savannah Corridor”. We want to study a crossroads of different Bantu expansions in the very heart of the Central-African rainforest, namely the eastern part of the Congo Basin (the Congo River and its tributaries up- and downstream of Kisangani until Bumba and Kindu). The region hosts multiple language groups from Bantu and other origin, complex ethnic identities and people practicing complementary subsistence strategies. Considering that farming is complicated in a rainforest environment, we will investigate the role of rivers in the settlement of these speech communities into the area, both as ways into the forest and as abundant source of animal protein (fish).
The project is multidisciplinary and will apply an integrated linguistic, anthropological and archaeological approach to study both present and past riverside communities in the Congo Basin. Historical comparative linguistics will offer insights into the historical relations between speech communities through language classification and the study of language contact, and will study specialized vocabulary to trace the history of river-related techniques, tools and knowledge. Anthropological research involves extensive fieldwork concerning ethnoecology, trade and/or exchange networks, sociocultural aspects of life at the riverside, and ethnohistory. Archaeologists will conduct surveys in the region of focus to provide a chrono-cultural framework.
Summary
The “Bantu Expansion”, a research theme within the precolonial history of Central Africa, unites scholars of different disciplines. Much research is focused on the initial expansions of Bantu subgroups, which are explained as farmers ever looking for new lands and therefore avoiding the rainforest, also in the recent research on the “Savannah Corridor”. We want to study a crossroads of different Bantu expansions in the very heart of the Central-African rainforest, namely the eastern part of the Congo Basin (the Congo River and its tributaries up- and downstream of Kisangani until Bumba and Kindu). The region hosts multiple language groups from Bantu and other origin, complex ethnic identities and people practicing complementary subsistence strategies. Considering that farming is complicated in a rainforest environment, we will investigate the role of rivers in the settlement of these speech communities into the area, both as ways into the forest and as abundant source of animal protein (fish).
The project is multidisciplinary and will apply an integrated linguistic, anthropological and archaeological approach to study both present and past riverside communities in the Congo Basin. Historical comparative linguistics will offer insights into the historical relations between speech communities through language classification and the study of language contact, and will study specialized vocabulary to trace the history of river-related techniques, tools and knowledge. Anthropological research involves extensive fieldwork concerning ethnoecology, trade and/or exchange networks, sociocultural aspects of life at the riverside, and ethnohistory. Archaeologists will conduct surveys in the region of focus to provide a chrono-cultural framework.
Max ERC Funding
1 427 821 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym BI-SDMoF
Project Bit-interleaved sigma-delta modulation over fiber
Researcher (PI) Piet DEMEESTER
Host Institution (HI) UNIVERSITEIT GENT
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary Network operators are struggling on how to release broadband mobile services in highly dense and hot-spot scenarios. The 5th generation of mobile networks is targeting per user downlink and uplink rates of 300 Mb/s and 50 Mb/s respectively. In ultra-dense environments such as stadiums, airports, shopping malls and tourist hot-spots, the aggregated bit rate becomes enormous. To make it more concrete, Belgium’s national football stadium (King Baudouin) is taken as example. The stadium can accommodate 50000 spectators. Even if an average bit-rate of only 50 Mb/s needs to be provided, an aggregated bit-rate of 2.5 Tb/s is required. Given the small area of a stadium (18 000 m2 seating area), this results in an astonishing capacity per area of 140 Tb/s/km2 or 140 Mb/s/m2. This is a 10-fold increase compared to area traffic capacity targeted in 5G and a 100-fold increase compared to the current 4G technologies.
In order to make this 10-fold increase happen, the BI-SDMoF proposal (Bit-Interleaved Sigma-Delta Modulation over Fiber) builds on patent pending technologies currently developed in the ATTO Advanced ERC grant (“A new concept for ultra-high capacity wireless networks”). Whereas the ATTO project is using floor and robot integrated antenna’s with a target density of 100 Gb/s/m2 and targets a long term market potential, the BI-SDMoF PoC will focus on applying basic components from the ATTO project in a 5G fiber-fronthaul Centralized Radio Access Network (C-RAN) and Distributed Antenna System (DAS) context that is much closer to the market. The target density is 150 Mb/s/m2 and a distributed Massive MIMO scenario is envisaged. As a PoC demonstrator a low power, low cost 28 GHz RRH (Radio Resource Head) supporting two antenna streams with four 400 MBd channels each will be designed and integrated in a small scale DAS (4 RRHs) demonstrator. Each RRH will support 25.6 Gbps mobile traffic and the complete DAS system will be tested in a stadium environment (Ghelamco).
Summary
Network operators are struggling on how to release broadband mobile services in highly dense and hot-spot scenarios. The 5th generation of mobile networks is targeting per user downlink and uplink rates of 300 Mb/s and 50 Mb/s respectively. In ultra-dense environments such as stadiums, airports, shopping malls and tourist hot-spots, the aggregated bit rate becomes enormous. To make it more concrete, Belgium’s national football stadium (King Baudouin) is taken as example. The stadium can accommodate 50000 spectators. Even if an average bit-rate of only 50 Mb/s needs to be provided, an aggregated bit-rate of 2.5 Tb/s is required. Given the small area of a stadium (18 000 m2 seating area), this results in an astonishing capacity per area of 140 Tb/s/km2 or 140 Mb/s/m2. This is a 10-fold increase compared to area traffic capacity targeted in 5G and a 100-fold increase compared to the current 4G technologies.
In order to make this 10-fold increase happen, the BI-SDMoF proposal (Bit-Interleaved Sigma-Delta Modulation over Fiber) builds on patent pending technologies currently developed in the ATTO Advanced ERC grant (“A new concept for ultra-high capacity wireless networks”). Whereas the ATTO project is using floor and robot integrated antenna’s with a target density of 100 Gb/s/m2 and targets a long term market potential, the BI-SDMoF PoC will focus on applying basic components from the ATTO project in a 5G fiber-fronthaul Centralized Radio Access Network (C-RAN) and Distributed Antenna System (DAS) context that is much closer to the market. The target density is 150 Mb/s/m2 and a distributed Massive MIMO scenario is envisaged. As a PoC demonstrator a low power, low cost 28 GHz RRH (Radio Resource Head) supporting two antenna streams with four 400 MBd channels each will be designed and integrated in a small scale DAS (4 RRHs) demonstrator. Each RRH will support 25.6 Gbps mobile traffic and the complete DAS system will be tested in a stadium environment (Ghelamco).
Max ERC Funding
149 970 €
Duration
Start date: 2019-09-01, End date: 2021-02-28
Project acronym BIONICbacteria
Project Integrating a novel layer of synthetic biology tools in Pseudomonas, inspired by bacterial viruses
Researcher (PI) Rob LAVIGNE
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Consolidator Grant (CoG), LS9, ERC-2018-COG
Summary As nature’s first bioengineers, bacteriophages have evolved to modify, adapt and control their bacterial hosts through billions of years of interactions. Indeed, like modern synthetic biologists aspire to do, bacteriophages already evade bacterial silencing of their xenogeneic DNA, subvert host gene expression, and co-opt both the central and peripheral metabolisms of their hosts. Studying these key insights from a molecular systems biology perspective, inspired us to develop these evolutionary fully-adapted phage mechanisms as a next-level layer of synthetic biology tools. Thus, BIONICbacteria will provide conceptual novel synthetic biology tools that allow direct manipulation of specific protein activity, post-translational modifications, RNA stability, and metabolite concentrations.
The goal of BIONICbacteria is to pioneer an unconventional way to perform synthetic biology, tapping an unlimited source of novel phage tools genetic circuits and phage modulators. To achieve these goals, we will apply and develop state-of-the-art technologies in molecular microbiology and focus on three principal aims:
(1) To exploit new phage-encoded genetic circuits as synthetic biology parts and as intricate biotechnological chassis.
(2) To build synthetic phage modulators (SPMs) as novel payloads to directly impact the bacterial metabolism in a targeted manner.
(3) To create designer bacteria by integrating SPMs-containing circuits into bacterial strains as proof-of-concepts for applications in industrial fermentations and vaccine design.
This proposed “plug-in” approach of evolutionary-adapted synthetic modules, will allow us to domesticate Pseudomonas strains in radically new ways. By building proofs-of-concept for applications in industrial fermentations and vaccine development, we address key problem in these areas with potentially high-gain solutions for society and industry.
Summary
As nature’s first bioengineers, bacteriophages have evolved to modify, adapt and control their bacterial hosts through billions of years of interactions. Indeed, like modern synthetic biologists aspire to do, bacteriophages already evade bacterial silencing of their xenogeneic DNA, subvert host gene expression, and co-opt both the central and peripheral metabolisms of their hosts. Studying these key insights from a molecular systems biology perspective, inspired us to develop these evolutionary fully-adapted phage mechanisms as a next-level layer of synthetic biology tools. Thus, BIONICbacteria will provide conceptual novel synthetic biology tools that allow direct manipulation of specific protein activity, post-translational modifications, RNA stability, and metabolite concentrations.
The goal of BIONICbacteria is to pioneer an unconventional way to perform synthetic biology, tapping an unlimited source of novel phage tools genetic circuits and phage modulators. To achieve these goals, we will apply and develop state-of-the-art technologies in molecular microbiology and focus on three principal aims:
(1) To exploit new phage-encoded genetic circuits as synthetic biology parts and as intricate biotechnological chassis.
(2) To build synthetic phage modulators (SPMs) as novel payloads to directly impact the bacterial metabolism in a targeted manner.
(3) To create designer bacteria by integrating SPMs-containing circuits into bacterial strains as proof-of-concepts for applications in industrial fermentations and vaccine design.
This proposed “plug-in” approach of evolutionary-adapted synthetic modules, will allow us to domesticate Pseudomonas strains in radically new ways. By building proofs-of-concept for applications in industrial fermentations and vaccine development, we address key problem in these areas with potentially high-gain solutions for society and industry.
Max ERC Funding
1 998 750 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym BREEDIT
Project A NOVEL BREEDING STRATEGY USING MULTIPLEX GENOME EDITING IN MAIZE
Researcher (PI) Dirk INZE
Host Institution (HI) VIB
Call Details Advanced Grant (AdG), LS9, ERC-2018-ADG
Summary Feeding the growing world population under changing climate conditions poses an unprecedented challenge on global agriculture and our current pace to breed new high yielding crop varieties is too low to face the imminent threats on food security. This ERC project proposes a novel crossing scheme that allows for an expeditious evaluation of combinations of potential yield contributing alleles by unifying ‘classical’ breeding with gene-centric molecular biology. The acronym BREEDIT, a word fusion of breeding and editing, reflects the basic concept of combining breeding with multiplex genome editing of yield related genes. By introducing plants with distinct combinations of genome edited mutations in more than 80 known yield related genes into a crossing scheme, the combinatorial effect of these mutations on plant growth and yield will be evaluated. Subsequent rounds of crossings will increase the number of stacked gene-edits per plant, thus increasing the combinatorial complexity. Phenotypic evaluations throughout plant development will be done on our in-house automated image-analysis based phenotyping platform. The nature and frequency of Cas9-mediated mutations in the entire plant collection will be characterised by multiplex amplicon sequencing to follow the efficiency of CRISPR-cas9 genome editing and to identify the underlying combinations of genes that cause beneficial phenotypes (genetic gain). The obtained knowledge on yield regulatory networks can be directly implemented into current molecular breeding programs and the project will provide the basis to develop targeted breeding schemes implementing the optimal combinations of beneficial alleles into elite material.
BREEDIT will be a major step forward in integrating basic knowledge on genes with plant breeding and has the potential to provoke a paradigm shift in improving crop yield.
Summary
Feeding the growing world population under changing climate conditions poses an unprecedented challenge on global agriculture and our current pace to breed new high yielding crop varieties is too low to face the imminent threats on food security. This ERC project proposes a novel crossing scheme that allows for an expeditious evaluation of combinations of potential yield contributing alleles by unifying ‘classical’ breeding with gene-centric molecular biology. The acronym BREEDIT, a word fusion of breeding and editing, reflects the basic concept of combining breeding with multiplex genome editing of yield related genes. By introducing plants with distinct combinations of genome edited mutations in more than 80 known yield related genes into a crossing scheme, the combinatorial effect of these mutations on plant growth and yield will be evaluated. Subsequent rounds of crossings will increase the number of stacked gene-edits per plant, thus increasing the combinatorial complexity. Phenotypic evaluations throughout plant development will be done on our in-house automated image-analysis based phenotyping platform. The nature and frequency of Cas9-mediated mutations in the entire plant collection will be characterised by multiplex amplicon sequencing to follow the efficiency of CRISPR-cas9 genome editing and to identify the underlying combinations of genes that cause beneficial phenotypes (genetic gain). The obtained knowledge on yield regulatory networks can be directly implemented into current molecular breeding programs and the project will provide the basis to develop targeted breeding schemes implementing the optimal combinations of beneficial alleles into elite material.
BREEDIT will be a major step forward in integrating basic knowledge on genes with plant breeding and has the potential to provoke a paradigm shift in improving crop yield.
Max ERC Funding
2 474 790 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym BrokenGenome
Project Breaking and rebuilding the genome: mechanistic rules for the dangerous game of sex.
Researcher (PI) Corentin CLAEYS BOUUAERT
Host Institution (HI) UNIVERSITE CATHOLIQUE DE LOUVAIN
Call Details Starting Grant (StG), LS1, ERC-2018-STG
Summary Sexual reproduction depends on the programmed induction of DNA double-strand breaks (DSBs) and their ensuing repair by homologous recombination. This complex process is essential for sexual reproduction because it ultimately allows the pairing and separation of homologous chromosomes during formation of haploid gametes. Although meiotic recombination has been investigated for decades, many of the underlying molecular processes remain unclear, largely due to the lack of biochemical studies. I have recently made important progress by, for the first time, successfully purifying proteins involved in two aspects of meiotic recombination: DSB formation and the final stage of formation of the crossovers that are a central raison-d’être of meiotic recombination. This has opened new avenues for future research that I intend to pursue in my own laboratory. Here, I propose a set of biochemical approaches, complemented by molecular genetics methods, to gain insights into four central problems: (i) How meiotic proteins collaborate to induce DSBs; (ii) How DSB proteins interact with components that form the axes of meiotic chromosomes; (iii) How proteins involved at later stages of recombination form crossovers; and (iv) How crossover proteins interact with components of synapsed chromosomes. For each problem, I will set up in vitro systems to probe the activities of the players involved, their interactions with DNA, and their assembly into macromolecular complexes. In addition, I propose to develop new methodology for identifying proteins that are associated with DNA that has undergone recombination-related DNA synthesis. My goal is to gain insights into the mechanisms that govern meiotic recombination. Importantly, these mechanisms are intimately linked not only to gamete formation, but also to the general recombination pathways that all cells use to maintain genome stability. In both contexts, our findings will be relevant to the development and avoidance of disease states.
Summary
Sexual reproduction depends on the programmed induction of DNA double-strand breaks (DSBs) and their ensuing repair by homologous recombination. This complex process is essential for sexual reproduction because it ultimately allows the pairing and separation of homologous chromosomes during formation of haploid gametes. Although meiotic recombination has been investigated for decades, many of the underlying molecular processes remain unclear, largely due to the lack of biochemical studies. I have recently made important progress by, for the first time, successfully purifying proteins involved in two aspects of meiotic recombination: DSB formation and the final stage of formation of the crossovers that are a central raison-d’être of meiotic recombination. This has opened new avenues for future research that I intend to pursue in my own laboratory. Here, I propose a set of biochemical approaches, complemented by molecular genetics methods, to gain insights into four central problems: (i) How meiotic proteins collaborate to induce DSBs; (ii) How DSB proteins interact with components that form the axes of meiotic chromosomes; (iii) How proteins involved at later stages of recombination form crossovers; and (iv) How crossover proteins interact with components of synapsed chromosomes. For each problem, I will set up in vitro systems to probe the activities of the players involved, their interactions with DNA, and their assembly into macromolecular complexes. In addition, I propose to develop new methodology for identifying proteins that are associated with DNA that has undergone recombination-related DNA synthesis. My goal is to gain insights into the mechanisms that govern meiotic recombination. Importantly, these mechanisms are intimately linked not only to gamete formation, but also to the general recombination pathways that all cells use to maintain genome stability. In both contexts, our findings will be relevant to the development and avoidance of disease states.
Max ERC Funding
1 499 075 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym CAFYR
Project Constructing Age for Young Readers
Researcher (PI) Vanessa JOOSEN
Host Institution (HI) UNIVERSITEIT ANTWERPEN
Call Details Starting Grant (StG), SH5, ERC-2018-STG
Summary Constructing Age for Young Readers (CAFYR)
CAFYR starts from the observations that Europe has recently witnessed a few pertinent crises in intergenerational tension, that age norms and ageism frequently go unchecked and that they are part of children’s socialization. It aims at developing pioneering research for understanding how age is constructed in cultural products. CAFYR focuses on fiction for young readers as a discourse that often naturalizes age norms as part of an engaging story and that is endorsed in educational contexts for contributing to children’s literacy, social and cultural development. The effect of three factors on the construction of age in children’s books is studied: the age of the author, the age of the intended reader, and the age of the real reader.
CAFYR aims to lay bare whether and how the age and aging process of children’s authors affect their construction of the life stages in their works. It will show how various crosswriters shape the stages in life differently for young and adult readers. It considers the age of young readers as varied in its own right, and investigates how age is constructed differently for children of different ages, from preschoolers to adolescents. Finally, it brings together readers of various stages in the life course in a reception study that will help understand how real readers construct age, during the reading process and in dialogue with each other. CAFYR also aims to break new theoretical and methodological ground. It offers an interdisciplinary approach that enriches children’s literature research with concepts and theories from age studies. It combines close reading strategies with distant reading and tools developed for digital text analysis. It provides a platform to people of different stages in life, contributing to their awareness about age, and facilitating and investigating dialogues about age, with the aim of ultimately fostering them more.
Summary
Constructing Age for Young Readers (CAFYR)
CAFYR starts from the observations that Europe has recently witnessed a few pertinent crises in intergenerational tension, that age norms and ageism frequently go unchecked and that they are part of children’s socialization. It aims at developing pioneering research for understanding how age is constructed in cultural products. CAFYR focuses on fiction for young readers as a discourse that often naturalizes age norms as part of an engaging story and that is endorsed in educational contexts for contributing to children’s literacy, social and cultural development. The effect of three factors on the construction of age in children’s books is studied: the age of the author, the age of the intended reader, and the age of the real reader.
CAFYR aims to lay bare whether and how the age and aging process of children’s authors affect their construction of the life stages in their works. It will show how various crosswriters shape the stages in life differently for young and adult readers. It considers the age of young readers as varied in its own right, and investigates how age is constructed differently for children of different ages, from preschoolers to adolescents. Finally, it brings together readers of various stages in the life course in a reception study that will help understand how real readers construct age, during the reading process and in dialogue with each other. CAFYR also aims to break new theoretical and methodological ground. It offers an interdisciplinary approach that enriches children’s literature research with concepts and theories from age studies. It combines close reading strategies with distant reading and tools developed for digital text analysis. It provides a platform to people of different stages in life, contributing to their awareness about age, and facilitating and investigating dialogues about age, with the aim of ultimately fostering them more.
Max ERC Funding
1 400 885 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym CANCERSTEM
Project Stem cells in epithelial cancer initiation and growth
Researcher (PI) Cédric Blanpain
Host Institution (HI) UNIVERSITE LIBRE DE BRUXELLES
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary Cancer is the result of a multi-step process requiring the accumulation of mutations in several genes. For most cancers, the target cells of oncogenic mutations are unknown. Adult stem cells (SCs) might be the initial target cells as they self-renew for extended periods of time, providing increased opportunity to accumulate the mutations required for cancer formation. Certain cancers contain cells characteristics of SC with high self-renewal capacities and the ability to reform the parental tumor upon transplantation. However, whether the initial oncogenic mutations arise in normal stem cells or in more differentiated cells that re-acquire stem cell-like properties remains to be determined. The demonstration that SCs are the target cells of the initial transforming events and that cancers contain cells with SC characteristics await the development of tools allowing for the isolation and characterization of normal adult SCs. In most epithelia from which cancers naturally arise, such tools are not yet available. We have recently developed novel methods to specifically mark and isolate multipotent epidermal slow-cycling SCs, making it now possible to determine the role of SC during epithelial cancer formation. In this project, we will use mice epidermis as a model to define the role of SC in epithelial cancer initiation and growth. Specifically, we will determine whether epithelial SCs are the initial target cells of oncogenic mutations during skin cancer formation, whether oncogenic mutations lead preferentially to skin cancer when they arise in SC rather than in more committed cells and whether cancer stem cells contribute to epithelial tumor growth and relapse after therapy.
Summary
Cancer is the result of a multi-step process requiring the accumulation of mutations in several genes. For most cancers, the target cells of oncogenic mutations are unknown. Adult stem cells (SCs) might be the initial target cells as they self-renew for extended periods of time, providing increased opportunity to accumulate the mutations required for cancer formation. Certain cancers contain cells characteristics of SC with high self-renewal capacities and the ability to reform the parental tumor upon transplantation. However, whether the initial oncogenic mutations arise in normal stem cells or in more differentiated cells that re-acquire stem cell-like properties remains to be determined. The demonstration that SCs are the target cells of the initial transforming events and that cancers contain cells with SC characteristics await the development of tools allowing for the isolation and characterization of normal adult SCs. In most epithelia from which cancers naturally arise, such tools are not yet available. We have recently developed novel methods to specifically mark and isolate multipotent epidermal slow-cycling SCs, making it now possible to determine the role of SC during epithelial cancer formation. In this project, we will use mice epidermis as a model to define the role of SC in epithelial cancer initiation and growth. Specifically, we will determine whether epithelial SCs are the initial target cells of oncogenic mutations during skin cancer formation, whether oncogenic mutations lead preferentially to skin cancer when they arise in SC rather than in more committed cells and whether cancer stem cells contribute to epithelial tumor growth and relapse after therapy.
Max ERC Funding
1 600 000 €
Duration
Start date: 2008-07-01, End date: 2013-12-31