Project acronym AEROSOL
Project Astrochemistry of old stars:direct probing of unique chemical laboratories
Researcher (PI) Leen Katrien Els Decin
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Consolidator Grant (CoG), PE9, ERC-2014-CoG
Summary The gas and dust in the interstellar medium (ISM) drive the chemical evolution of galaxies, the formation of stars and planets, and the synthesis of complex prebiotic molecules. The prime birth places for this interstellar material are the winds of evolved (super)giant stars. These winds are unique chemical laboratories, in which a large variety of gas and dust species radially expand away from the star.
Recent progress on the observations of these winds has been impressive thanks to Herschel and ALMA. The next challenge is to unravel the wealth of chemical information contained in these data. This is an ambitious task since (1) a plethora of physical and chemical processes interact in a complex way, (2) laboratory data to interpret these interactions are lacking, and (3) theoretical tools to analyse the data do not meet current needs.
To boost the knowledge of the physics and chemistry characterizing these winds, I propose a world-leading multi-disciplinary project combining (1) high-quality data, (2) novel theoretical wind models, and (3) targeted laboratory experiments. The aim is to pinpoint the dominant chemical pathways, unravel the transition from gas-phase to dust species, elucidate the role of clumps on the overall wind structure, and study the reciprocal effect between various dynamical and chemical phenomena.
Now is the right time for this ambitious project thanks to the availability of (1) high-quality multi-wavelength data, including ALMA and Herschel data of the PI, (2) supercomputers enabling a homogeneous analysis of the data using sophisticated theoretical wind models, and (3) novel laboratory equipment to measure the gas-phase reaction rates of key species.
This project will have far-reaching impact on (1) the field of evolved stars, (2) the understanding of the chemical lifecycle of the ISM, (3) chemical studies of dynamically more complex systems, such as exoplanets, protostars, supernovae etc., and (4) it will guide new instrument development.
Summary
The gas and dust in the interstellar medium (ISM) drive the chemical evolution of galaxies, the formation of stars and planets, and the synthesis of complex prebiotic molecules. The prime birth places for this interstellar material are the winds of evolved (super)giant stars. These winds are unique chemical laboratories, in which a large variety of gas and dust species radially expand away from the star.
Recent progress on the observations of these winds has been impressive thanks to Herschel and ALMA. The next challenge is to unravel the wealth of chemical information contained in these data. This is an ambitious task since (1) a plethora of physical and chemical processes interact in a complex way, (2) laboratory data to interpret these interactions are lacking, and (3) theoretical tools to analyse the data do not meet current needs.
To boost the knowledge of the physics and chemistry characterizing these winds, I propose a world-leading multi-disciplinary project combining (1) high-quality data, (2) novel theoretical wind models, and (3) targeted laboratory experiments. The aim is to pinpoint the dominant chemical pathways, unravel the transition from gas-phase to dust species, elucidate the role of clumps on the overall wind structure, and study the reciprocal effect between various dynamical and chemical phenomena.
Now is the right time for this ambitious project thanks to the availability of (1) high-quality multi-wavelength data, including ALMA and Herschel data of the PI, (2) supercomputers enabling a homogeneous analysis of the data using sophisticated theoretical wind models, and (3) novel laboratory equipment to measure the gas-phase reaction rates of key species.
This project will have far-reaching impact on (1) the field of evolved stars, (2) the understanding of the chemical lifecycle of the ISM, (3) chemical studies of dynamically more complex systems, such as exoplanets, protostars, supernovae etc., and (4) it will guide new instrument development.
Max ERC Funding
2 605 897 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym AFDMATS
Project Anton Francesco Doni – Multimedia Archive Texts and Sources
Researcher (PI) Giovanna Rizzarelli
Host Institution (HI) SCUOLA NORMALE SUPERIORE
Call Details Starting Grant (StG), SH4, ERC-2007-StG
Summary This project aims at creating a multimedia archive of the printed works of Anton Francesco Doni, who was not only an author but also a typographer, a publisher and a member of the Giolito and Marcolini’s editorial staff. The analysis of Doni’s work may be a good way to investigate appropriation, text rewriting and image reusing practices which are typical of several authors of the 16th Century, as clearly shown by the critics in the last decades. This project intends to bring to light the wide range of impulses from which Doni’s texts are generated, with a great emphasis on the figurative aspect. The encoding of these texts will be carried out using the TEI (Text Encoding Initiative) guidelines, which will enable any single text to interact with a range of intertextual references both at a local level (inside the same text) and at a macrostructural level (references to other texts by Doni or to other authors). The elements that will emerge from the textual encoding concern: A) The use of images Real images: the complex relation between Doni’s writing and the xylographies available in Marcolini’s printing-house or belonging to other collections. Mental images: the remarkable presence of verbal images, as descriptions, ekphràseis, figurative visions, dreams and iconographic allusions not accompanied by illustrations, but related to a recognizable visual repertoire or to real images that will be reproduced. B) The use of sources A parallel archive of the texts most used by Doni will be created. Digital anastatic reproductions of the 16th-Century editions known by Doni will be provided whenever available. The various forms of intertextuality will be divided into the following typologies: allusions; citations; rewritings; plagiarisms; self-quotations. Finally, the different forms of narrative (tales, short stories, anecdotes, lyrics) and the different idiomatic expressions (proverbial forms and wellerisms) will also be encoded.
Summary
This project aims at creating a multimedia archive of the printed works of Anton Francesco Doni, who was not only an author but also a typographer, a publisher and a member of the Giolito and Marcolini’s editorial staff. The analysis of Doni’s work may be a good way to investigate appropriation, text rewriting and image reusing practices which are typical of several authors of the 16th Century, as clearly shown by the critics in the last decades. This project intends to bring to light the wide range of impulses from which Doni’s texts are generated, with a great emphasis on the figurative aspect. The encoding of these texts will be carried out using the TEI (Text Encoding Initiative) guidelines, which will enable any single text to interact with a range of intertextual references both at a local level (inside the same text) and at a macrostructural level (references to other texts by Doni or to other authors). The elements that will emerge from the textual encoding concern: A) The use of images Real images: the complex relation between Doni’s writing and the xylographies available in Marcolini’s printing-house or belonging to other collections. Mental images: the remarkable presence of verbal images, as descriptions, ekphràseis, figurative visions, dreams and iconographic allusions not accompanied by illustrations, but related to a recognizable visual repertoire or to real images that will be reproduced. B) The use of sources A parallel archive of the texts most used by Doni will be created. Digital anastatic reproductions of the 16th-Century editions known by Doni will be provided whenever available. The various forms of intertextuality will be divided into the following typologies: allusions; citations; rewritings; plagiarisms; self-quotations. Finally, the different forms of narrative (tales, short stories, anecdotes, lyrics) and the different idiomatic expressions (proverbial forms and wellerisms) will also be encoded.
Max ERC Funding
559 200 €
Duration
Start date: 2008-08-01, End date: 2012-07-31
Project acronym AFFORDS-HIGHER
Project Skilled Intentionality for 'Higher' Embodied Cognition: Joining forces with a field of affordances in flux
Researcher (PI) Dirk Willem Rietveld
Host Institution (HI) ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Call Details Starting Grant (StG), SH4, ERC-2015-STG
Summary In many situations experts act adequately, yet without deliberation. Architects e.g, immediately sense opportunities offered by the site of a new project. One could label these manifestations of expert intuition as ‘higher-level’ cognition, but still these experts act unreflectively. The aim of my project is to develop the Skilled Intentionality Framework (SIF), a new conceptual framework for the field of embodied/enactive cognitive science (Chemero, 2009; Thompson, 2007). I argue that affordances - possibilities for action provided by our surroundings - are highly significant in cases of unreflective and reflective ‘higher’ cognition. Skilled Intentionality is skilled coordination with multiple affordances simultaneously.
The two central ideas behind this proposal are (a) that episodes of skilled ‘higher’ cognition can be understood as responsiveness to affordances for ‘higher’ cognition and (b) that our surroundings are highly resourceful and contribute to skillful action and cognition in a far more fundamental way than is generally acknowledged. I use embedded philosophical research in a particular practice of architecture to shed new light on the ways in which affordances for ‘higher’ cognition support creative imagination, anticipation, explicit planning and self-reflection.
The Skilled Intentionality Framework is groundbreaking in relating findings established at several complementary levels of analysis: philosophy/phenomenology, ecological psychology, affective science and neurodynamics.
Empirical findings thought to be exclusively valid for everyday unreflective action can now be used to explain skilled ‘higher’ cognition as well. Moreover, SIF brings both the context and the social back into cognitive science. I will show SIF’s relevance for Friston’s work on the anticipating brain, and apply it in the domain of architecture and public health. SIF will radically widen the scope of the increasingly influential field of embodied cognitive science.
Summary
In many situations experts act adequately, yet without deliberation. Architects e.g, immediately sense opportunities offered by the site of a new project. One could label these manifestations of expert intuition as ‘higher-level’ cognition, but still these experts act unreflectively. The aim of my project is to develop the Skilled Intentionality Framework (SIF), a new conceptual framework for the field of embodied/enactive cognitive science (Chemero, 2009; Thompson, 2007). I argue that affordances - possibilities for action provided by our surroundings - are highly significant in cases of unreflective and reflective ‘higher’ cognition. Skilled Intentionality is skilled coordination with multiple affordances simultaneously.
The two central ideas behind this proposal are (a) that episodes of skilled ‘higher’ cognition can be understood as responsiveness to affordances for ‘higher’ cognition and (b) that our surroundings are highly resourceful and contribute to skillful action and cognition in a far more fundamental way than is generally acknowledged. I use embedded philosophical research in a particular practice of architecture to shed new light on the ways in which affordances for ‘higher’ cognition support creative imagination, anticipation, explicit planning and self-reflection.
The Skilled Intentionality Framework is groundbreaking in relating findings established at several complementary levels of analysis: philosophy/phenomenology, ecological psychology, affective science and neurodynamics.
Empirical findings thought to be exclusively valid for everyday unreflective action can now be used to explain skilled ‘higher’ cognition as well. Moreover, SIF brings both the context and the social back into cognitive science. I will show SIF’s relevance for Friston’s work on the anticipating brain, and apply it in the domain of architecture and public health. SIF will radically widen the scope of the increasingly influential field of embodied cognitive science.
Max ERC Funding
1 499 850 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym Age Asymmetry
Project Age-Selective Segregation of Organelles
Researcher (PI) Pekka Aleksi Katajisto
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS3, ERC-2015-STG
Summary Our tissues are constantly renewed by stem cells. Over time, stem cells accumulate cellular damage that will compromise renewal and results in aging. As stem cells can divide asymmetrically, segregation of harmful factors to the differentiating daughter cell could be one possible mechanism for slowing damage accumulation in the stem cell. However, current evidence for such mechanisms comes mainly from analogous findings in yeast, and studies have concentrated only on few types of cellular damage.
I hypothesize that the chronological age of a subcellular component is a proxy for all the damage it has sustained. In order to secure regeneration, mammalian stem cells may therefore specifically sort old cellular material asymmetrically. To study this, I have developed a novel strategy and tools to address the age-selective segregation of any protein in stem cell division. Using this approach, I have already discovered that stem-like cells of the human mammary epithelium indeed apportion chronologically old mitochondria asymmetrically in cell division, and enrich old mitochondria to the differentiating daughter cell. We will investigate the mechanisms underlying this novel phenomenon, and its relevance for mammalian aging.
We will first identify how old and young mitochondria differ, and how stem cells recognize them to facilitate the asymmetric segregation. Next, we will analyze the extent of asymmetric age-selective segregation by targeting several other subcellular compartments in a stem cell division. Finally, we will determine whether the discovered age-selective segregation is a general property of stem cell in vivo, and it's functional relevance for maintenance of stem cells and tissue regeneration. Our discoveries may open new possibilities to target aging associated functional decline by induction of asymmetric age-selective organelle segregation.
Summary
Our tissues are constantly renewed by stem cells. Over time, stem cells accumulate cellular damage that will compromise renewal and results in aging. As stem cells can divide asymmetrically, segregation of harmful factors to the differentiating daughter cell could be one possible mechanism for slowing damage accumulation in the stem cell. However, current evidence for such mechanisms comes mainly from analogous findings in yeast, and studies have concentrated only on few types of cellular damage.
I hypothesize that the chronological age of a subcellular component is a proxy for all the damage it has sustained. In order to secure regeneration, mammalian stem cells may therefore specifically sort old cellular material asymmetrically. To study this, I have developed a novel strategy and tools to address the age-selective segregation of any protein in stem cell division. Using this approach, I have already discovered that stem-like cells of the human mammary epithelium indeed apportion chronologically old mitochondria asymmetrically in cell division, and enrich old mitochondria to the differentiating daughter cell. We will investigate the mechanisms underlying this novel phenomenon, and its relevance for mammalian aging.
We will first identify how old and young mitochondria differ, and how stem cells recognize them to facilitate the asymmetric segregation. Next, we will analyze the extent of asymmetric age-selective segregation by targeting several other subcellular compartments in a stem cell division. Finally, we will determine whether the discovered age-selective segregation is a general property of stem cell in vivo, and it's functional relevance for maintenance of stem cells and tissue regeneration. Our discoveries may open new possibilities to target aging associated functional decline by induction of asymmetric age-selective organelle segregation.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym AgeConsolidate
Project The Missing Link of Episodic Memory Decline in Aging: The Role of Inefficient Systems Consolidation
Researcher (PI) Anders Martin FJELL
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Consolidator Grant (CoG), SH4, ERC-2016-COG
Summary Which brain mechanisms are responsible for the faith of the memories we make with age, whether they wither or stay, and in what form? Episodic memory function does decline with age. While this decline can have multiple causes, research has focused almost entirely on encoding and retrieval processes, largely ignoring a third critical process– consolidation. The objective of AgeConsolidate is to provide this missing link, by combining novel experimental cognitive paradigms with neuroimaging in a longitudinal large-scale attempt to directly test how age-related changes in consolidation processes in the brain impact episodic memory decline. The ambitious aims of the present proposal are two-fold:
(1) Use recent advances in memory consolidation theory to achieve an elaborate model of episodic memory deficits in aging
(2) Use aging as a model to uncover how structural and functional brain changes affect episodic memory consolidation in general
The novelty of the project lies in the synthesis of recent methodological advances and theoretical models for episodic memory consolidation to explain age-related decline, by employing a unique combination of a range of different techniques and approaches. This is ground-breaking, in that it aims at taking our understanding of the brain processes underlying episodic memory decline in aging to a new level, while at the same time advancing our theoretical understanding of how episodic memories are consolidated in the human brain. To obtain this outcome, I will test the main hypothesis of the project: Brain processes of episodic memory consolidation are less effective in older adults, and this can account for a significant portion of the episodic memory decline in aging. This will be answered by six secondary hypotheses, with 1-3 experiments or tasks designated to address each hypothesis, focusing on functional and structural MRI, positron emission tomography data and sleep experiments to target consolidation from different angles.
Summary
Which brain mechanisms are responsible for the faith of the memories we make with age, whether they wither or stay, and in what form? Episodic memory function does decline with age. While this decline can have multiple causes, research has focused almost entirely on encoding and retrieval processes, largely ignoring a third critical process– consolidation. The objective of AgeConsolidate is to provide this missing link, by combining novel experimental cognitive paradigms with neuroimaging in a longitudinal large-scale attempt to directly test how age-related changes in consolidation processes in the brain impact episodic memory decline. The ambitious aims of the present proposal are two-fold:
(1) Use recent advances in memory consolidation theory to achieve an elaborate model of episodic memory deficits in aging
(2) Use aging as a model to uncover how structural and functional brain changes affect episodic memory consolidation in general
The novelty of the project lies in the synthesis of recent methodological advances and theoretical models for episodic memory consolidation to explain age-related decline, by employing a unique combination of a range of different techniques and approaches. This is ground-breaking, in that it aims at taking our understanding of the brain processes underlying episodic memory decline in aging to a new level, while at the same time advancing our theoretical understanding of how episodic memories are consolidated in the human brain. To obtain this outcome, I will test the main hypothesis of the project: Brain processes of episodic memory consolidation are less effective in older adults, and this can account for a significant portion of the episodic memory decline in aging. This will be answered by six secondary hypotheses, with 1-3 experiments or tasks designated to address each hypothesis, focusing on functional and structural MRI, positron emission tomography data and sleep experiments to target consolidation from different angles.
Max ERC Funding
1 999 482 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym AgeingStemCellFate
Project The Role of Ectopic Adipocyte Progenitors in Age-related Stem Cell Dysfunction, Systemic Inflammation, and Metabolic Disease
Researcher (PI) Tim Julius Schulz
Host Institution (HI) DEUTSCHES INSTITUT FUER ERNAEHRUNGSFORSCHUNG POTSDAM REHBRUECKE
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary Ageing is accompanied by ectopic white adipose tissue depositions in skeletal muscle and other anatomical locations, such as brown adipose tissue and the bone marrow. Ectopic fat accrual contributes to organ dysfunction, systemic insulin resistance, and other perturbations that have been implicated in metabolic diseases.
This research proposal aims to identify the regulatory cues that control the development of ectopic progenitor cells that give rise to this type of fat. It is hypothesized that an age-related dysfunction of the stem cell niche leads to an imbalance between (1) tissue-specific stem cells and (2) fibroblast-like, primarily adipogenic progenitors that reside within many tissues. Novel methodologies that assess stem/progenitor cell characteristics on the single cell level will be combined with animal models of lineage tracing to determine the developmental origin of these adipogenic progenitors and processes that regulate their function.
Notch signalling is a key signalling pathway that relies on direct physical interaction to control stem cell fate. It is proposed that impaired Notch activity contributes to the phenotypical shift of precursor cell distribution in aged tissues.
Lastly, the role of the stem cell niche in ectopic adipocyte progenitor formation will be analyzed. External signals originating from the surrounding niche cells regulate the developmental fate of stem cells. Secreted factors and their role in the formation of ectopic adipocyte precursors during senescence will be identified using a combination of biochemical and systems biology approaches.
Accomplishment of these studies will help to understand the basic processes of stem cell ageing and identify mechanisms of age-related functional decline in tissue regeneration. By targeting the population of tissue-resident adipogenic progenitor cells, therapeutic strategies could be developed to counteract metabolic complications associated with the ageing process.
Summary
Ageing is accompanied by ectopic white adipose tissue depositions in skeletal muscle and other anatomical locations, such as brown adipose tissue and the bone marrow. Ectopic fat accrual contributes to organ dysfunction, systemic insulin resistance, and other perturbations that have been implicated in metabolic diseases.
This research proposal aims to identify the regulatory cues that control the development of ectopic progenitor cells that give rise to this type of fat. It is hypothesized that an age-related dysfunction of the stem cell niche leads to an imbalance between (1) tissue-specific stem cells and (2) fibroblast-like, primarily adipogenic progenitors that reside within many tissues. Novel methodologies that assess stem/progenitor cell characteristics on the single cell level will be combined with animal models of lineage tracing to determine the developmental origin of these adipogenic progenitors and processes that regulate their function.
Notch signalling is a key signalling pathway that relies on direct physical interaction to control stem cell fate. It is proposed that impaired Notch activity contributes to the phenotypical shift of precursor cell distribution in aged tissues.
Lastly, the role of the stem cell niche in ectopic adipocyte progenitor formation will be analyzed. External signals originating from the surrounding niche cells regulate the developmental fate of stem cells. Secreted factors and their role in the formation of ectopic adipocyte precursors during senescence will be identified using a combination of biochemical and systems biology approaches.
Accomplishment of these studies will help to understand the basic processes of stem cell ageing and identify mechanisms of age-related functional decline in tissue regeneration. By targeting the population of tissue-resident adipogenic progenitor cells, therapeutic strategies could be developed to counteract metabolic complications associated with the ageing process.
Max ERC Funding
1 496 444 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym AGESPACE
Project SPATIAL NAVIGATION – A UNIQUE WINDOW INTO MECHANISMS OF COGNITIVE AGEING
Researcher (PI) Thomas Wolbers
Host Institution (HI) DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Call Details Starting Grant (StG), SH4, ERC-2013-StG
Summary "By 2040, the European population aged over 60 will rise to 290 million, with those estimated to have dementia to 15.9 million. These dramatic demographic changes will pose huge challenges to health care systems, hence a detailed understanding of age-related cognitive and neurobiological changes is essential for helping elderly populations maintain independence. However, while existing research into cognitive ageing has carefully characterised developmental trajectories of functions such as memory and processing speed, one key cognitive ability that is particularly relevant to everyday functioning has received very little attention: In surveys, elderly people often report substantial declines in navigational abilities such as problems with finding one’s way in a novel environment. Such deficits severely restrict the mobility of elderly people and affect physical activity and social participation, but the underlying behavioural and neuronal mechanisms are poorly understood.
In this proposal, I will take a new approach to cognitive ageing that will bridge the gap between animal neurobiology and human cognitive neuroscience. With support from the ERC, I will create a team that will characterise the mechanisms mediating age-related changes in navigational processing in humans. The project will focus on three structures that perform key computations for spatial navigation, form a closely interconnected triadic network, and are particularly sensitive to the ageing process. Crucially, the team will employ an interdisciplinary methodological approach that combines mathematical modelling, brain imaging and innovative data analysis techniques with novel virtual environment technology, which allows for rigorous testing of predictions derived from animal findings. Finally, the proposal also incorporates a translational project aimed at improving spatial mnemonic functioning with a behavioural intervention, which provides a direct test of functional relevance and societal impact."
Summary
"By 2040, the European population aged over 60 will rise to 290 million, with those estimated to have dementia to 15.9 million. These dramatic demographic changes will pose huge challenges to health care systems, hence a detailed understanding of age-related cognitive and neurobiological changes is essential for helping elderly populations maintain independence. However, while existing research into cognitive ageing has carefully characterised developmental trajectories of functions such as memory and processing speed, one key cognitive ability that is particularly relevant to everyday functioning has received very little attention: In surveys, elderly people often report substantial declines in navigational abilities such as problems with finding one’s way in a novel environment. Such deficits severely restrict the mobility of elderly people and affect physical activity and social participation, but the underlying behavioural and neuronal mechanisms are poorly understood.
In this proposal, I will take a new approach to cognitive ageing that will bridge the gap between animal neurobiology and human cognitive neuroscience. With support from the ERC, I will create a team that will characterise the mechanisms mediating age-related changes in navigational processing in humans. The project will focus on three structures that perform key computations for spatial navigation, form a closely interconnected triadic network, and are particularly sensitive to the ageing process. Crucially, the team will employ an interdisciplinary methodological approach that combines mathematical modelling, brain imaging and innovative data analysis techniques with novel virtual environment technology, which allows for rigorous testing of predictions derived from animal findings. Finally, the proposal also incorporates a translational project aimed at improving spatial mnemonic functioning with a behavioural intervention, which provides a direct test of functional relevance and societal impact."
Max ERC Funding
1 318 990 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym AGINGSEXDIFF
Project Aging Differently: Understanding Sex Differences in Reproductive, Demographic and Functional Senescence
Researcher (PI) Alexei Maklakov
Host Institution (HI) Uppsala University
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a
long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not
only in how long they live and when they start to senesce, but also in how they react to
environmental interventions aimed at prolonging their life span or decelerating the onset of aging.
Therefore, sex differences in life span and aging have important implications beyond the questions
posed by fundamental science. Both evolutionary reasons and medical implications of sex
differences in demographic, reproductive and physiological senescence are and will be crucial
targets of present and future research in the biology of aging. Here I propose a two-step approach
that can provide a significant breakthrough in our understanding of the biological basis of sex
differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific
mortality rate in sex differences in aging by developing a series of targeted experimental
evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I
address the role of intra-locus sexual conflict in the evolution of aging by combining novel
methodology from nutritional ecology – the Geometric Framework – with artificial selection
approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will
directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the
adaptive evolution of diet choice. By combining techniques from evolutionary biology and
nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to
the training of young scientists in this rapidly developing field.
Summary
Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a
long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not
only in how long they live and when they start to senesce, but also in how they react to
environmental interventions aimed at prolonging their life span or decelerating the onset of aging.
Therefore, sex differences in life span and aging have important implications beyond the questions
posed by fundamental science. Both evolutionary reasons and medical implications of sex
differences in demographic, reproductive and physiological senescence are and will be crucial
targets of present and future research in the biology of aging. Here I propose a two-step approach
that can provide a significant breakthrough in our understanding of the biological basis of sex
differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific
mortality rate in sex differences in aging by developing a series of targeted experimental
evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I
address the role of intra-locus sexual conflict in the evolution of aging by combining novel
methodology from nutritional ecology – the Geometric Framework – with artificial selection
approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will
directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the
adaptive evolution of diet choice. By combining techniques from evolutionary biology and
nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to
the training of young scientists in this rapidly developing field.
Max ERC Funding
1 391 904 €
Duration
Start date: 2010-12-01, End date: 2016-05-31
Project acronym AGRISCENTS
Project Scents and sensibility in agriculture: exploiting specificity in herbivore- and pathogen-induced plant volatiles for real-time crop monitoring
Researcher (PI) Theodoor Turlings
Host Institution (HI) UNIVERSITE DE NEUCHATEL
Call Details Advanced Grant (AdG), LS9, ERC-2017-ADG
Summary Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to:
• Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations.
• Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath.
• Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots.
In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.
Summary
Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to:
• Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations.
• Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath.
• Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots.
In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.
Max ERC Funding
2 498 086 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym AHRIMMUNITY
Project The influence of Aryl hydrocarbon receptor ligands on protective and pathological immune responses
Researcher (PI) Brigitta Stockinger
Host Institution (HI) MEDICAL RESEARCH COUNCIL
Call Details Advanced Grant (AdG), LS6, ERC-2008-AdG
Summary The Aryl hydrocarbon receptor is an evolutionary conserved widely expressed transcription factor that mediates the toxicity of a substantial variety of exogenous toxins, but is also stimulated by endogenous physiological ligands. While it is known that this receptor mediates the toxicity of dioxin, this is unlikely to be its physiological function. We have recently identified selective expression of AhR in the Th17 subset of effector CD4 T cells. Ligation of AhR by a candidate endogenous ligand (FICZ) which is a UV metabolite of tryptophan causes expansion of Th17 cells and the induction of IL-22 production. As a consequence, AhR ligation will exacerbate autoimmune diseases such as experimental autoimmune encephalomyelitis. Little is known so far about the impact of AhR ligands on IL-17/IL-22 mediated immune defense functions. IL-22 is considered a pro-inflammatory Th17 cytokine, which is involved in the etiology of psoriasis, but it has also been shown to be a survival factor for epithelial cells. AhR is polymorphic and defined as high or low affinity receptor for dioxin leading to the classification of high and low responder mouse strains based on defined mutations. In humans similar polymorphisms exist and although on the whole human AhR is thought to be of low affinity in humans, there are identified mutations that confer high responder status. No correlations have been made with Th17 mediated immune responses in mice and humans. This study aims to investigate the role of AhR ligands and polymorphisms in autoimmunity as well as protective immune responses using both mouse models and human samples from normal controls as well as psoriasis patients.
Summary
The Aryl hydrocarbon receptor is an evolutionary conserved widely expressed transcription factor that mediates the toxicity of a substantial variety of exogenous toxins, but is also stimulated by endogenous physiological ligands. While it is known that this receptor mediates the toxicity of dioxin, this is unlikely to be its physiological function. We have recently identified selective expression of AhR in the Th17 subset of effector CD4 T cells. Ligation of AhR by a candidate endogenous ligand (FICZ) which is a UV metabolite of tryptophan causes expansion of Th17 cells and the induction of IL-22 production. As a consequence, AhR ligation will exacerbate autoimmune diseases such as experimental autoimmune encephalomyelitis. Little is known so far about the impact of AhR ligands on IL-17/IL-22 mediated immune defense functions. IL-22 is considered a pro-inflammatory Th17 cytokine, which is involved in the etiology of psoriasis, but it has also been shown to be a survival factor for epithelial cells. AhR is polymorphic and defined as high or low affinity receptor for dioxin leading to the classification of high and low responder mouse strains based on defined mutations. In humans similar polymorphisms exist and although on the whole human AhR is thought to be of low affinity in humans, there are identified mutations that confer high responder status. No correlations have been made with Th17 mediated immune responses in mice and humans. This study aims to investigate the role of AhR ligands and polymorphisms in autoimmunity as well as protective immune responses using both mouse models and human samples from normal controls as well as psoriasis patients.
Max ERC Funding
1 242 352 €
Duration
Start date: 2009-02-01, End date: 2014-01-31