Project acronym 2STEPPARKIN
Project A novel two-step model for neurodegeneration in Parkinson’s disease
Researcher (PI) Emi Nagoshi
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Starting Grant (StG), LS5, ERC-2012-StG_20111109
Summary Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Despite the advances in gene discovery associated with PD, the knowledge of the PD pathogenesis is largely limited to the involvement of these genes in the generic cell death pathways, and why degeneration is specific to DA neurons and why the degeneration is progressive remain enigmatic. Broad goal of our work is therefore to elucidate the mechanisms underlying specific and progressive DA neuron degeneration in PD. Our new Drosophila model of PD ⎯Fer2 gene loss-of-function mutation⎯ is unusually well suited to address these questions. Fer2 mutants exhibit specific and progressive death of brain DA neurons as well as severe locomotor defects and short life span. Strikingly, the death of DA neuron is initiated in a small cluster of Fer2-expressing DA neurons and subsequently propagates to Fer2-negative DA neurons. We therefore propose a novel two-step model of the neurodegeneration in PD: primary cell death occurs in a specific subset of dopamindegic neurons that are genetically defined, and subsequently the failure of the neuronal connectivity triggers and propagates secondary cell death to remaining DA neurons. In this research, we will test this hypothesis and investigate the underlying molecular mechanisms. This will be the first study to examine circuit-dependency in DA neuron degeneration. Our approach will use a combination of non-biased genomic techniques and candidate-based screening, in addition to the powerful Drosophila genetic toolbox. Furthermore, to test this hypothesis beyond the Drosophila model, we will establish new mouse models of PD that exhibit progressive DA neuron degeneration. Outcome of this research will likely revolutionize the understanding of PD pathogenesis and open an avenue toward the discovery of effective therapy strategies against PD.
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Despite the advances in gene discovery associated with PD, the knowledge of the PD pathogenesis is largely limited to the involvement of these genes in the generic cell death pathways, and why degeneration is specific to DA neurons and why the degeneration is progressive remain enigmatic. Broad goal of our work is therefore to elucidate the mechanisms underlying specific and progressive DA neuron degeneration in PD. Our new Drosophila model of PD ⎯Fer2 gene loss-of-function mutation⎯ is unusually well suited to address these questions. Fer2 mutants exhibit specific and progressive death of brain DA neurons as well as severe locomotor defects and short life span. Strikingly, the death of DA neuron is initiated in a small cluster of Fer2-expressing DA neurons and subsequently propagates to Fer2-negative DA neurons. We therefore propose a novel two-step model of the neurodegeneration in PD: primary cell death occurs in a specific subset of dopamindegic neurons that are genetically defined, and subsequently the failure of the neuronal connectivity triggers and propagates secondary cell death to remaining DA neurons. In this research, we will test this hypothesis and investigate the underlying molecular mechanisms. This will be the first study to examine circuit-dependency in DA neuron degeneration. Our approach will use a combination of non-biased genomic techniques and candidate-based screening, in addition to the powerful Drosophila genetic toolbox. Furthermore, to test this hypothesis beyond the Drosophila model, we will establish new mouse models of PD that exhibit progressive DA neuron degeneration. Outcome of this research will likely revolutionize the understanding of PD pathogenesis and open an avenue toward the discovery of effective therapy strategies against PD.
Max ERC Funding
1 518 960 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym AGELESS
Project Comparative genomics / ‘wildlife’ transcriptomics uncovers the mechanisms of halted ageing in mammals
Researcher (PI) Emma Teeling
Host Institution (HI) UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Call Details Starting Grant (StG), LS2, ERC-2012-StG_20111109
Summary "Ageing is the gradual and irreversible breakdown of living systems associated with the advancement of time, which leads to an increase in vulnerability and eventual mortality. Despite recent advances in ageing research, the intrinsic complexity of the ageing process has prevented a full understanding of this process, therefore, ageing remains a grand challenge in contemporary biology. In AGELESS, we will tackle this challenge by uncovering the molecular mechanisms of halted ageing in a unique model system, the bats. Bats are the longest-lived mammals relative to their body size, and defy the ‘rate-of-living’ theories as they use twice as much the energy as other species of considerable size, but live far longer. This suggests that bats have some underlying mechanisms that may explain their exceptional longevity. In AGELESS, we will identify the molecular mechanisms that enable mammals to achieve extraordinary longevity, using state-of-the-art comparative genomic methodologies focused on bats. We will identify, using population transcriptomics and telomere/mtDNA genomics, the molecular changes that occur in an ageing wild population of bats to uncover how bats ‘age’ so slowly compared with other mammals. In silico whole genome analyses, field based ageing transcriptomic data, mtDNA and telomeric studies will be integrated and analysed using a networks approach, to ascertain how these systems interact to halt ageing. For the first time, we will be able to utilize the diversity seen within nature to identify key molecular targets and regions that regulate and control ageing in mammals. AGELESS will provide a deeper understanding of the causal mechanisms of ageing, potentially uncovering the crucial molecular pathways that can be modified to halt, alleviate and perhaps even reverse this process in man."
Summary
"Ageing is the gradual and irreversible breakdown of living systems associated with the advancement of time, which leads to an increase in vulnerability and eventual mortality. Despite recent advances in ageing research, the intrinsic complexity of the ageing process has prevented a full understanding of this process, therefore, ageing remains a grand challenge in contemporary biology. In AGELESS, we will tackle this challenge by uncovering the molecular mechanisms of halted ageing in a unique model system, the bats. Bats are the longest-lived mammals relative to their body size, and defy the ‘rate-of-living’ theories as they use twice as much the energy as other species of considerable size, but live far longer. This suggests that bats have some underlying mechanisms that may explain their exceptional longevity. In AGELESS, we will identify the molecular mechanisms that enable mammals to achieve extraordinary longevity, using state-of-the-art comparative genomic methodologies focused on bats. We will identify, using population transcriptomics and telomere/mtDNA genomics, the molecular changes that occur in an ageing wild population of bats to uncover how bats ‘age’ so slowly compared with other mammals. In silico whole genome analyses, field based ageing transcriptomic data, mtDNA and telomeric studies will be integrated and analysed using a networks approach, to ascertain how these systems interact to halt ageing. For the first time, we will be able to utilize the diversity seen within nature to identify key molecular targets and regions that regulate and control ageing in mammals. AGELESS will provide a deeper understanding of the causal mechanisms of ageing, potentially uncovering the crucial molecular pathways that can be modified to halt, alleviate and perhaps even reverse this process in man."
Max ERC Funding
1 499 768 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym ANALYTICAL SOCIOLOGY
Project Analytical Sociology: Theoretical Developments and Empirical Research
Researcher (PI) Mats Peter Hedström
Host Institution (HI) LINKOPINGS UNIVERSITET
Call Details Advanced Grant (AdG), SH2, ERC-2012-ADG_20120411
Summary This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction.
One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link.
The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed.
Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.
Summary
This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction.
One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link.
The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed.
Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.
Max ERC Funding
1 745 098 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym Antivessel-T-Cells
Project Development of Vascular-Disrupting Lymphocyte Therapy for Tumours
Researcher (PI) Georgios Coukos
Host Institution (HI) CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS
Call Details Advanced Grant (AdG), LS7, ERC-2012-ADG_20120314
Summary T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory.
I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.
Summary
T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory.
I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-08-01, End date: 2018-07-31
Project acronym Attoclock
Project Clocking fundamental attosecond electron dynamics
Researcher (PI) Ursula Keller
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE2, ERC-2012-ADG_20120216
Summary The attoclock is a powerful, new, and unconventional tool to study fundamental attosecond dynamics on an atomic scale. We established its potential by using the first attoclock to measure the tunneling delay time in laser-induced ionization of helium and argon atoms, with surprising results. Building on these first proof-of-principle measurements, I propose to amplify and expand this tool concept to explore the following key questions: How fast can light liberate electrons from a single atom, a single molecule, or a solid-state system? Related are more questions: How fast can an electron tunnel through a potential barrier? How fast is a multi-photon absorption process? How fast is single-photon photoemission? Many of these questions will undoubtedly spark more questions – revealing deeper and more detailed insights on the dynamics of some of the most fundamental and relevant optoelectronic processes.
There are still many unknown and unexplored areas here. Theory has failed to offer definitive answers. Simulations based on the exact time-dependent Schrödinger equation have not been possible in most cases. Therefore one uses approximations and simpler models to capture the essential physics. Such semi-classical models potentially will help to understand attosecond energy and charge transport in larger molecular systems. Indeed the attoclock provides a unique tool to explore different semi-classical models.
For example, the question of whether electron tunneling through an energetically forbidden region takes a finite time or is instantaneous has been subject to ongoing debate for the last sixty years. The tunnelling process, charge transfer, and energy transport all play key roles in electronics, energy conversion, chemical and biological reactions, and fundamental processes important for improved information, health, and energy technologies. We believe the attoclock can help refine and resolve key models for many of these important underlying attosecond processes.
Summary
The attoclock is a powerful, new, and unconventional tool to study fundamental attosecond dynamics on an atomic scale. We established its potential by using the first attoclock to measure the tunneling delay time in laser-induced ionization of helium and argon atoms, with surprising results. Building on these first proof-of-principle measurements, I propose to amplify and expand this tool concept to explore the following key questions: How fast can light liberate electrons from a single atom, a single molecule, or a solid-state system? Related are more questions: How fast can an electron tunnel through a potential barrier? How fast is a multi-photon absorption process? How fast is single-photon photoemission? Many of these questions will undoubtedly spark more questions – revealing deeper and more detailed insights on the dynamics of some of the most fundamental and relevant optoelectronic processes.
There are still many unknown and unexplored areas here. Theory has failed to offer definitive answers. Simulations based on the exact time-dependent Schrödinger equation have not been possible in most cases. Therefore one uses approximations and simpler models to capture the essential physics. Such semi-classical models potentially will help to understand attosecond energy and charge transport in larger molecular systems. Indeed the attoclock provides a unique tool to explore different semi-classical models.
For example, the question of whether electron tunneling through an energetically forbidden region takes a finite time or is instantaneous has been subject to ongoing debate for the last sixty years. The tunnelling process, charge transfer, and energy transport all play key roles in electronics, energy conversion, chemical and biological reactions, and fundamental processes important for improved information, health, and energy technologies. We believe the attoclock can help refine and resolve key models for many of these important underlying attosecond processes.
Max ERC Funding
2 319 796 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym ATTOSCOPE
Project Measuring attosecond electron dynamics in molecules
Researcher (PI) Hans Jakob Wörner
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), PE4, ERC-2012-StG_20111012
Summary "The goal of the present proposal is to realize measurements of electronic dynamics in polyatomic
molecules with attosecond temporal resolution (1 as = 10^-18s). We propose to study electronic
rearrangements following photoexcitation, charge migration in a molecular chain induced by
ionization and non-adiabatic multi-electron dynamics in an intense laser field. The grand question
addressed by this research is the characterization of electron correlations which control the shape, properties and function of molecules. In all three proposed projects, a time-domain approach appears to be the most suitable since it reduces complex molecular dynamics to the purely electronic dynamics by exploiting the hierarchy of motional time scales. Experimentally, we propose to realize an innovative experimental setup. A few-cycle infrared (IR) pulse will be used to generate attosecond pulses in the extreme-ultraviolet (XUV) by high-harmonic generation. The IR pulse will be separated from the XUV by means of an innovative interferometer. Additionally, it will permit the introduction of a controlled attosecond delay between the two pulses. We propose to use the attosecond pulses as a tool to look inside individual IR- or UV-field cycles to better understand light-matter interactions. Time-resolved pump-probe experiments will be carried out on polyatomic molecules by detecting the energy and angular distribution of photoelectrons in a velocity-map imaging spectrometer. These experiments are expected to provide new insights
into the dynamics of multi-electron systems along with new results for the validation and
improvement of theoretical models. Multi-electron dynamics is indeed a very complex subject
on its own and even more so in the presence of strong laser fields. The proposed experiments
directly address theses challenges and are expected to provide new insights that will be beneficial to a wide range of scientific research areas."
Summary
"The goal of the present proposal is to realize measurements of electronic dynamics in polyatomic
molecules with attosecond temporal resolution (1 as = 10^-18s). We propose to study electronic
rearrangements following photoexcitation, charge migration in a molecular chain induced by
ionization and non-adiabatic multi-electron dynamics in an intense laser field. The grand question
addressed by this research is the characterization of electron correlations which control the shape, properties and function of molecules. In all three proposed projects, a time-domain approach appears to be the most suitable since it reduces complex molecular dynamics to the purely electronic dynamics by exploiting the hierarchy of motional time scales. Experimentally, we propose to realize an innovative experimental setup. A few-cycle infrared (IR) pulse will be used to generate attosecond pulses in the extreme-ultraviolet (XUV) by high-harmonic generation. The IR pulse will be separated from the XUV by means of an innovative interferometer. Additionally, it will permit the introduction of a controlled attosecond delay between the two pulses. We propose to use the attosecond pulses as a tool to look inside individual IR- or UV-field cycles to better understand light-matter interactions. Time-resolved pump-probe experiments will be carried out on polyatomic molecules by detecting the energy and angular distribution of photoelectrons in a velocity-map imaging spectrometer. These experiments are expected to provide new insights
into the dynamics of multi-electron systems along with new results for the validation and
improvement of theoretical models. Multi-electron dynamics is indeed a very complex subject
on its own and even more so in the presence of strong laser fields. The proposed experiments
directly address theses challenges and are expected to provide new insights that will be beneficial to a wide range of scientific research areas."
Max ERC Funding
1 999 992 €
Duration
Start date: 2012-09-01, End date: 2017-08-31
Project acronym BIOFINDER
Project New biomarkers for Alzheimer’s & Parkinson’s diseases - key tools for early diagnosis and drug development
Researcher (PI) Oskar Hansson
Host Institution (HI) LUNDS UNIVERSITET
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
Summary Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity.
AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets.
We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays.
New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging
Summary
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity.
AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets.
We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays.
New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging
Max ERC Funding
1 500 000 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym BioProbe
Project "VERTICAL MICROFLUIDIC PROBE: A nanoliter ""Swiss army knife"" for chemistry and physics at biological interfaces"
Researcher (PI) Govindkrishna Govind Kaigala
Host Institution (HI) IBM RESEARCH GMBH
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
Summary Life is fundamentally characterised by order, compartmentalisation and biochemical reactions, which occurs at the right place right time – within, on the surface and between cells. Only a proportion of life processes can be addressed with contemporary approaches like liquid encapsulations (e.g. droplets) or engineering compartments (e.g. scaffolds). I believe these approaches are severely limited. I am convinced that a technique to study, work and locally probe adherent cells & tissues at micrometer distances from cell surfaces in “open space” would represent a major advance for the biology of biointerfaces. I therefore propose a non-contact, scanning technology, which spatially confines nanoliter volumes of chemicals for interacting with cells at the µm-length scale. This technology called the vertical microfluidic probe (vMFP) – that I developed at IBM-Zurich – shapes liquid on surfaces hydrodynamically and is compatible with samples on Petri dishes & microtiter plates. The project is organized in 4 themes:
(1) Advancing the vMFP by understanding the interaction of liquid flows with biointerfaces, integrating functional elements (e.g. heaters/electrodes, cell traps) & precision control.
(2) Developing a higher resolution method to stain tissue sections for multiple markers & better quality information.
(3) Retrieving rare elements such as circulating tumor cells from biologically diverse libraries.
(4) Patterning cells for applications in regenerative medicine.
Since cells & tissues will no longer be limited by closed systems, the vMFP will enable a completely new range of experiments to be performed in a highly interactive, versatile & precise manner – this approach departs from classical “closed” microfluidics. It is very likely that such a tool by providing multifunctional capabilities akin to the proverbial ‘Swiss army knife’ will be a unique facilitator for investigations of previously unapproachable problems in cell biology & the life science.
Summary
Life is fundamentally characterised by order, compartmentalisation and biochemical reactions, which occurs at the right place right time – within, on the surface and between cells. Only a proportion of life processes can be addressed with contemporary approaches like liquid encapsulations (e.g. droplets) or engineering compartments (e.g. scaffolds). I believe these approaches are severely limited. I am convinced that a technique to study, work and locally probe adherent cells & tissues at micrometer distances from cell surfaces in “open space” would represent a major advance for the biology of biointerfaces. I therefore propose a non-contact, scanning technology, which spatially confines nanoliter volumes of chemicals for interacting with cells at the µm-length scale. This technology called the vertical microfluidic probe (vMFP) – that I developed at IBM-Zurich – shapes liquid on surfaces hydrodynamically and is compatible with samples on Petri dishes & microtiter plates. The project is organized in 4 themes:
(1) Advancing the vMFP by understanding the interaction of liquid flows with biointerfaces, integrating functional elements (e.g. heaters/electrodes, cell traps) & precision control.
(2) Developing a higher resolution method to stain tissue sections for multiple markers & better quality information.
(3) Retrieving rare elements such as circulating tumor cells from biologically diverse libraries.
(4) Patterning cells for applications in regenerative medicine.
Since cells & tissues will no longer be limited by closed systems, the vMFP will enable a completely new range of experiments to be performed in a highly interactive, versatile & precise manner – this approach departs from classical “closed” microfluidics. It is very likely that such a tool by providing multifunctional capabilities akin to the proverbial ‘Swiss army knife’ will be a unique facilitator for investigations of previously unapproachable problems in cell biology & the life science.
Max ERC Funding
1 488 600 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym BuildNet
Project Smart Building Networks
Researcher (PI) Colin Jones
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE7, ERC-2012-StG_20111012
Summary The Smart Building Networks (BuildNet) program will develop optimizing controllers capable of coordinating the flow of power to and from large networks of smart buildings in order to offer critical services to the power grid. The network will make use of the thermal storage of the structures and on-site micro generation capabilities of next-generation buildings, as well as the electrical capacity of attached electric vehicles in order to intelligently control the interaction between the network of buildings and the grid. The wide range of electric utility applications, such as wind capacity firming or congestion relief, that will be possible as a result of this coordinated control will in turn allow a significant increase in the percentage of European power generated from destabilizing renewable sources.
Technologically, BuildNet will be built around optimization-based or model predictive control (MPC), a paradigm that is ideally suited to the task of incorporating the current network state and forward-looking information into an optimal decision-making process. The project team will develop novel distributed MPC controllers that utilize the flexibility in the consumption, storage and generation of a distributed network of buildings by exploiting the extensive experience of the PI in optimization-based control and MPC for energy efficient buildings.
Because of its theoretically grounded optimization-based control approach, holistic view of building systems and connected networks, as well as a future-looking technological scope, BuildNet's outputs will deliver impact and be relevant to researchers and practitioners alike.
Summary
The Smart Building Networks (BuildNet) program will develop optimizing controllers capable of coordinating the flow of power to and from large networks of smart buildings in order to offer critical services to the power grid. The network will make use of the thermal storage of the structures and on-site micro generation capabilities of next-generation buildings, as well as the electrical capacity of attached electric vehicles in order to intelligently control the interaction between the network of buildings and the grid. The wide range of electric utility applications, such as wind capacity firming or congestion relief, that will be possible as a result of this coordinated control will in turn allow a significant increase in the percentage of European power generated from destabilizing renewable sources.
Technologically, BuildNet will be built around optimization-based or model predictive control (MPC), a paradigm that is ideally suited to the task of incorporating the current network state and forward-looking information into an optimal decision-making process. The project team will develop novel distributed MPC controllers that utilize the flexibility in the consumption, storage and generation of a distributed network of buildings by exploiting the extensive experience of the PI in optimization-based control and MPC for energy efficient buildings.
Because of its theoretically grounded optimization-based control approach, holistic view of building systems and connected networks, as well as a future-looking technological scope, BuildNet's outputs will deliver impact and be relevant to researchers and practitioners alike.
Max ERC Funding
1 460 232 €
Duration
Start date: 2012-12-01, End date: 2017-11-30
Project acronym CACTUS
Project developmental social Cognition and ACTion UnderStanding
Researcher (PI) Kjell Gustaf Gredebäck
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), SH4, ERC-2012-StG_20111124
Summary Humans are social creatures throughout life. This proposal aims to advance our knowledge of the mechanisms that mediate understanding of others’ actions from a developmental perspective. A special emphasis will be devoted to mirror neuron and teleological frameworks. The former framework focuses on reciprocal motor activation during action execution and observation whereas the later framework emphasizes the application of abstract principles to observed events. The mechanisms that guide both processes will be investigated in isolation, but special attention will also be devoted to understanding how these diverse forms of action understanding jointly contribute to action understanding. The project encompasses three essential research objectives, illustrated by three research questions. How do mirror neuron and teleological processes influence action understanding? How does action understanding enable social action evaluation (empathy and pro-social preferences)? How is action understanding expressed during real-life social interactions? These questions will be addressed by presenting infants and toddlers with social events of varying complexity (from simple actions and animated sequences to complex everyday social events), relating empirical findings to predictions derived from the teleological and motor cognitive frameworks. The overarching aim is to provide a computational model of early emerging social cognitive capabilities, with a focus on action understanding and action evaluation, while passively observing others and while partaking in social interactions with others.
Summary
Humans are social creatures throughout life. This proposal aims to advance our knowledge of the mechanisms that mediate understanding of others’ actions from a developmental perspective. A special emphasis will be devoted to mirror neuron and teleological frameworks. The former framework focuses on reciprocal motor activation during action execution and observation whereas the later framework emphasizes the application of abstract principles to observed events. The mechanisms that guide both processes will be investigated in isolation, but special attention will also be devoted to understanding how these diverse forms of action understanding jointly contribute to action understanding. The project encompasses three essential research objectives, illustrated by three research questions. How do mirror neuron and teleological processes influence action understanding? How does action understanding enable social action evaluation (empathy and pro-social preferences)? How is action understanding expressed during real-life social interactions? These questions will be addressed by presenting infants and toddlers with social events of varying complexity (from simple actions and animated sequences to complex everyday social events), relating empirical findings to predictions derived from the teleological and motor cognitive frameworks. The overarching aim is to provide a computational model of early emerging social cognitive capabilities, with a focus on action understanding and action evaluation, while passively observing others and while partaking in social interactions with others.
Max ERC Funding
1 498 920 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
