Project acronym 3DWATERWAVES
Project Mathematical aspects of three-dimensional water waves with vorticity
Researcher (PI) Erik Torsten Wahlen
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE1, ERC-2015-STG
Summary The goal of this project is to develop a mathematical theory for steady three-dimensional water waves with vorticity. The mathematical model consists of the incompressible Euler equations with a free surface, and vorticity is important for modelling the interaction of surface waves with non-uniform currents. In the two-dimensional case, there has been a lot of progress on water waves with vorticity in the last decade. This progress has mainly been based on the stream function formulation, in which the problem is reformulated as a nonlinear elliptic free boundary problem. An analogue of this formulation is not available in three dimensions, and the theory has therefore so far been restricted to irrotational flow. In this project we seek to go beyond this restriction using two different approaches. In the first approach we will adapt methods which have been used to construct three-dimensional ideal flows with vorticity in domains with a fixed boundary to the free boundary context (for example Beltrami flows). In the second approach we will develop methods which are new even in the case of a fixed boundary, by performing a detailed study of the structure of the equations close to a given shear flow using ideas from infinite-dimensional bifurcation theory. This involves handling infinitely many resonances.
Summary
The goal of this project is to develop a mathematical theory for steady three-dimensional water waves with vorticity. The mathematical model consists of the incompressible Euler equations with a free surface, and vorticity is important for modelling the interaction of surface waves with non-uniform currents. In the two-dimensional case, there has been a lot of progress on water waves with vorticity in the last decade. This progress has mainly been based on the stream function formulation, in which the problem is reformulated as a nonlinear elliptic free boundary problem. An analogue of this formulation is not available in three dimensions, and the theory has therefore so far been restricted to irrotational flow. In this project we seek to go beyond this restriction using two different approaches. In the first approach we will adapt methods which have been used to construct three-dimensional ideal flows with vorticity in domains with a fixed boundary to the free boundary context (for example Beltrami flows). In the second approach we will develop methods which are new even in the case of a fixed boundary, by performing a detailed study of the structure of the equations close to a given shear flow using ideas from infinite-dimensional bifurcation theory. This involves handling infinitely many resonances.
Max ERC Funding
1 203 627 €
Duration
Start date: 2016-03-01, End date: 2022-02-28
Project acronym AROMA-CFD
Project Advanced Reduced Order Methods with Applications in Computational Fluid Dynamics
Researcher (PI) Gianluigi Rozza
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Country Italy
Call Details Consolidator Grant (CoG), PE1, ERC-2015-CoG
Summary The aim of AROMA-CFD is to create a team of scientists at SISSA for the development of Advanced Reduced Order Modelling techniques with a focus in Computational Fluid Dynamics (CFD), in order to face and overcome many current limitations of the state of the art and improve the capabilities of reduced order methodologies for more demanding applications in industrial, medical and applied sciences contexts. AROMA-CFD deals with strong methodological developments in numerical analysis, with a special emphasis on mathematical modelling and extensive exploitation of computational science and engineering. Several tasks have been identified to tackle important problems and open questions in reduced order modelling: study of bifurcations and instabilities in flows, increasing Reynolds number and guaranteeing stability, moving towards turbulent flows, considering complex geometrical parametrizations of shapes as computational domains into extended networks. A reduced computational and geometrical framework will be developed for nonlinear inverse problems, focusing on optimal flow control, shape optimization and uncertainty quantification. Further, all the advanced developments in reduced order modelling for CFD will be delivered for applications in multiphysics, such as fluid-structure interaction problems and general coupled phenomena involving inviscid, viscous and thermal flows, solids and porous media. The advanced developed framework within AROMA-CFD will provide attractive capabilities for several industrial and medical applications (e.g. aeronautical, mechanical, naval, off-shore, wind, sport, biomedical engineering, and cardiovascular surgery as well), combining high performance computing (in dedicated supercomputing centers) and advanced reduced order modelling (in common devices) to guarantee real time computing and visualization. A new open source software library for AROMA-CFD will be created: ITHACA, In real Time Highly Advanced Computational Applications.
Summary
The aim of AROMA-CFD is to create a team of scientists at SISSA for the development of Advanced Reduced Order Modelling techniques with a focus in Computational Fluid Dynamics (CFD), in order to face and overcome many current limitations of the state of the art and improve the capabilities of reduced order methodologies for more demanding applications in industrial, medical and applied sciences contexts. AROMA-CFD deals with strong methodological developments in numerical analysis, with a special emphasis on mathematical modelling and extensive exploitation of computational science and engineering. Several tasks have been identified to tackle important problems and open questions in reduced order modelling: study of bifurcations and instabilities in flows, increasing Reynolds number and guaranteeing stability, moving towards turbulent flows, considering complex geometrical parametrizations of shapes as computational domains into extended networks. A reduced computational and geometrical framework will be developed for nonlinear inverse problems, focusing on optimal flow control, shape optimization and uncertainty quantification. Further, all the advanced developments in reduced order modelling for CFD will be delivered for applications in multiphysics, such as fluid-structure interaction problems and general coupled phenomena involving inviscid, viscous and thermal flows, solids and porous media. The advanced developed framework within AROMA-CFD will provide attractive capabilities for several industrial and medical applications (e.g. aeronautical, mechanical, naval, off-shore, wind, sport, biomedical engineering, and cardiovascular surgery as well), combining high performance computing (in dedicated supercomputing centers) and advanced reduced order modelling (in common devices) to guarantee real time computing and visualization. A new open source software library for AROMA-CFD will be created: ITHACA, In real Time Highly Advanced Computational Applications.
Max ERC Funding
1 656 579 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym BioMNP
Project Understanding the interaction between metal nanoparticles and biological membranes
Researcher (PI) Giulia Rossi
Host Institution (HI) UNIVERSITA DEGLI STUDI DI GENOVA
Country Italy
Call Details Starting Grant (StG), PE3, ERC-2015-STG
Summary The BioMNP objective is the molecular-level understanding of the interactions between surface functionalized metal nanoparticles and biological membranes, by means of cutting-edge computational techniques and new molecular models.
Metal nanoparticles (NP) play more and more important roles in pharmaceutical and medical technology as diagnostic or therapeutic devices. Metal NPs can nowadays be engineered in a multitude of shapes, sizes and compositions, and they can be decorated with an almost infinite variety of functionalities. Despite such technological advances, there is still poor understanding of the molecular processes that drive the interactions of metal NPs with cells. Cell membranes are the first barrier encountered by NPs entering living organisms. The understanding and control of the interaction of nanoparticles with biological membranes is therefore of paramount importance to understand the molecular basis of the NP biological effects.
BioMNP will go beyond the state of the art by rationalizing the complex interplay of NP size, composition, functionalization and aggregation state during the interaction with model biomembranes. Membranes, in turn, will be modelled at an increasing level of complexity in terms of lipid composition and phase. BioMNP will rely on cutting-edge simulation techniques and facilities, and develop new coarse-grained models grounded on finer-level atomistic simulations, to study the NP-membrane interactions on an extremely large range of length and time scales.
BioMNP will benefit from important and complementary experimental collaborations, will propose interpretations of the available experimental data and make predictions to guide the design of functional, non-toxic metal nanoparticles for biomedical applications. BioMNP aims at answering fundamental questions at the crossroads of physics, biology and chemistry. Its results will have an impact on nanomedicine, toxicology, nanotechnology and material sciences.
Summary
The BioMNP objective is the molecular-level understanding of the interactions between surface functionalized metal nanoparticles and biological membranes, by means of cutting-edge computational techniques and new molecular models.
Metal nanoparticles (NP) play more and more important roles in pharmaceutical and medical technology as diagnostic or therapeutic devices. Metal NPs can nowadays be engineered in a multitude of shapes, sizes and compositions, and they can be decorated with an almost infinite variety of functionalities. Despite such technological advances, there is still poor understanding of the molecular processes that drive the interactions of metal NPs with cells. Cell membranes are the first barrier encountered by NPs entering living organisms. The understanding and control of the interaction of nanoparticles with biological membranes is therefore of paramount importance to understand the molecular basis of the NP biological effects.
BioMNP will go beyond the state of the art by rationalizing the complex interplay of NP size, composition, functionalization and aggregation state during the interaction with model biomembranes. Membranes, in turn, will be modelled at an increasing level of complexity in terms of lipid composition and phase. BioMNP will rely on cutting-edge simulation techniques and facilities, and develop new coarse-grained models grounded on finer-level atomistic simulations, to study the NP-membrane interactions on an extremely large range of length and time scales.
BioMNP will benefit from important and complementary experimental collaborations, will propose interpretations of the available experimental data and make predictions to guide the design of functional, non-toxic metal nanoparticles for biomedical applications. BioMNP aims at answering fundamental questions at the crossroads of physics, biology and chemistry. Its results will have an impact on nanomedicine, toxicology, nanotechnology and material sciences.
Max ERC Funding
1 131 250 €
Duration
Start date: 2016-04-01, End date: 2021-03-31
Project acronym BOOST
Project Biomimetic trick to re-balance Osteblast-Osteoclast loop in osteoporoSis treatment: a Topological and materials driven approach
Researcher (PI) Chiara Silvia Vitale Brovarone
Host Institution (HI) POLITECNICO DI TORINO
Country Italy
Call Details Consolidator Grant (CoG), PE8, ERC-2015-CoG
Summary One out of 5 people in their fifties will experience a bone fracture due to osteoporosis (OP)-induced fragility in their lifetime. The OP socio-economic burden is dramatic and involves tens of millions of people in the EU, with a steadily increasing number due to population ageing. Current treatments entail drug-therapy coupled with a healthy lifestyle but OP fractures need mechanical fixation to rapidly achieve union: the contribution of biomaterial scientists in this field is still far from taking its expected leading role in cutting-edge research. Bone remodelling is a well-coordinated process of bone resorption by osteoclasts followed by the production of new bone by osteoblasts. This process occurs continuously throughout life in a coupling with a positive balance during growth and negative with ageing, which can result in OP. We believe that an architecture driven stimulation of the osteoclast/osteoblast coupling, with an avant-garde focus on osteoclasts activity, is the key to success in treating unbalanced bone remodelling. We aim to manufacture a scaffold that mimics healthy bone features which will establish a new microenvironment favoring a properly stimulated and active population of osteoclasts and osteoblasts, i.e. a well-balanced bone cooperation. After 5 years we will be able to prove the efficacy of this approach. A benchmark will be set up for OP fracture treatment and for the realization of smart bone substitutes that will be able to locally “trick” aged bone cells stimulating them to act as healthy ones. BOOST results will have an unprecedented impact on the scientific research community, opening a new approach to set up smart, biomimetic strategies to treat aged, unbalanced bone tissues and to reduce OP-associated disabilities and financial burdens.
Summary
One out of 5 people in their fifties will experience a bone fracture due to osteoporosis (OP)-induced fragility in their lifetime. The OP socio-economic burden is dramatic and involves tens of millions of people in the EU, with a steadily increasing number due to population ageing. Current treatments entail drug-therapy coupled with a healthy lifestyle but OP fractures need mechanical fixation to rapidly achieve union: the contribution of biomaterial scientists in this field is still far from taking its expected leading role in cutting-edge research. Bone remodelling is a well-coordinated process of bone resorption by osteoclasts followed by the production of new bone by osteoblasts. This process occurs continuously throughout life in a coupling with a positive balance during growth and negative with ageing, which can result in OP. We believe that an architecture driven stimulation of the osteoclast/osteoblast coupling, with an avant-garde focus on osteoclasts activity, is the key to success in treating unbalanced bone remodelling. We aim to manufacture a scaffold that mimics healthy bone features which will establish a new microenvironment favoring a properly stimulated and active population of osteoclasts and osteoblasts, i.e. a well-balanced bone cooperation. After 5 years we will be able to prove the efficacy of this approach. A benchmark will be set up for OP fracture treatment and for the realization of smart bone substitutes that will be able to locally “trick” aged bone cells stimulating them to act as healthy ones. BOOST results will have an unprecedented impact on the scientific research community, opening a new approach to set up smart, biomimetic strategies to treat aged, unbalanced bone tissues and to reduce OP-associated disabilities and financial burdens.
Max ERC Funding
1 977 500 €
Duration
Start date: 2016-05-01, End date: 2022-06-30
Project acronym BOPNIE
Project Boundary value problems for nonlinear integrable equations
Researcher (PI) Jonatan Carl Anders Lenells
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Country Sweden
Call Details Consolidator Grant (CoG), PE1, ERC-2015-CoG
Summary The purpose of this project is to develop new methods for solving boundary value problems (BVPs) for nonlinear integrable partial differential equations (PDEs). Integrable PDEs can be analyzed by means of the Inverse Scattering Transform, whose introduction was one of the most important developments in the theory of nonlinear PDEs in the 20th century. Until the 1990s the inverse scattering methodology was pursued almost entirely for pure initial-value problems. However, in many laboratory and field situations, the solution is generated by what corresponds to the imposition of boundary conditions rather than initial conditions. Thus, an understanding of BVPs is crucial.
In an exciting sequence of events taking place in the last two decades, new tools have become available to deal with BVPs for integrable PDEs. Although some important issues have already been resolved, several major problems remain open.
The aim of this project is to solve a number of these open problems and to find solutions of BVPs which were heretofore not solvable. More precisely, the proposal has eight objectives:
1. Develop methods for solving problems with time-periodic boundary conditions.
2. Answer some long-standing open questions raised by series of wave-tank experiments 35 years ago.
3. Develop a new approach for the study of space-periodic solutions.
4. Develop new approaches for the analysis of BVPs for equations with 3 x 3-matrix Lax pairs.
5. Derive new asymptotic formulas by using a nonlinear version of the steepest descent method.
6. Construct disk and disk/black-hole solutions of the stationary axisymmetric Einstein equations.
7. Solve a BVP in Einstein's theory of relativity describing two colliding gravitational waves.
8. Extend the above methods to BVPs in higher dimensions.
Summary
The purpose of this project is to develop new methods for solving boundary value problems (BVPs) for nonlinear integrable partial differential equations (PDEs). Integrable PDEs can be analyzed by means of the Inverse Scattering Transform, whose introduction was one of the most important developments in the theory of nonlinear PDEs in the 20th century. Until the 1990s the inverse scattering methodology was pursued almost entirely for pure initial-value problems. However, in many laboratory and field situations, the solution is generated by what corresponds to the imposition of boundary conditions rather than initial conditions. Thus, an understanding of BVPs is crucial.
In an exciting sequence of events taking place in the last two decades, new tools have become available to deal with BVPs for integrable PDEs. Although some important issues have already been resolved, several major problems remain open.
The aim of this project is to solve a number of these open problems and to find solutions of BVPs which were heretofore not solvable. More precisely, the proposal has eight objectives:
1. Develop methods for solving problems with time-periodic boundary conditions.
2. Answer some long-standing open questions raised by series of wave-tank experiments 35 years ago.
3. Develop a new approach for the study of space-periodic solutions.
4. Develop new approaches for the analysis of BVPs for equations with 3 x 3-matrix Lax pairs.
5. Derive new asymptotic formulas by using a nonlinear version of the steepest descent method.
6. Construct disk and disk/black-hole solutions of the stationary axisymmetric Einstein equations.
7. Solve a BVP in Einstein's theory of relativity describing two colliding gravitational waves.
8. Extend the above methods to BVPs in higher dimensions.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-05-01, End date: 2022-02-28
Project acronym Born-Immune
Project Shaping of the Human Immune System by Primal Environmental Exposures In the Newborn Child
Researcher (PI) Klas Erik Petter Brodin
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Starting Grant (StG), LS6, ERC-2015-STG
Summary Immune systems are highly variable, but the sources of this variation are poorly understood. Genetic variation only explains a minor fraction of this, and we are unable to accurately predict the risk of immune mediated disease or severe infection in any given individual. I recently found that immune cells and proteins in healthy twins vary because of non-heritable influences (infections, vaccines, microbiota etc.), with only minor influences from heritable factors (Brodin, et al, Cell 2015). When and how such environmental influences shape our immune system is now important to understand. Birth represents the most transformational change in environment during the life of any individual. I propose, that environmental influences at birth, and during the first months of life could be particularly influential by imprinting on the regulatory mechanisms forming in the developing immune system. Adaptive changes in immune cell frequencies and functional states induced by early-life exposures could determine both the immune competence of the newborn, but potentially also its long-term trajectory towards immunological health or disease. Here, I propose a study of 1000 newborn children, followed longitudinally during their first 1000 days of life. By monitoring immune profiles and recording many environmental influences, we hope to understand how early life exposures can influence human immune system development. We have established a new assay based on Mass Cytometry and necessary data analysis tools (Brodin, et al, PNAS 2014), to simultaneously monitor the frequencies, phenotypes and functional states of more than 200 blood immune cell populations from only 100 microliters of blood. By monitoring environmental influences at regular follow-up visits, by questionnaires, serum measurements of infection, and gut microbiome sequencing, we aim to provide the most comprehensive analysis to date of immune system development in newborn children.
Summary
Immune systems are highly variable, but the sources of this variation are poorly understood. Genetic variation only explains a minor fraction of this, and we are unable to accurately predict the risk of immune mediated disease or severe infection in any given individual. I recently found that immune cells and proteins in healthy twins vary because of non-heritable influences (infections, vaccines, microbiota etc.), with only minor influences from heritable factors (Brodin, et al, Cell 2015). When and how such environmental influences shape our immune system is now important to understand. Birth represents the most transformational change in environment during the life of any individual. I propose, that environmental influences at birth, and during the first months of life could be particularly influential by imprinting on the regulatory mechanisms forming in the developing immune system. Adaptive changes in immune cell frequencies and functional states induced by early-life exposures could determine both the immune competence of the newborn, but potentially also its long-term trajectory towards immunological health or disease. Here, I propose a study of 1000 newborn children, followed longitudinally during their first 1000 days of life. By monitoring immune profiles and recording many environmental influences, we hope to understand how early life exposures can influence human immune system development. We have established a new assay based on Mass Cytometry and necessary data analysis tools (Brodin, et al, PNAS 2014), to simultaneously monitor the frequencies, phenotypes and functional states of more than 200 blood immune cell populations from only 100 microliters of blood. By monitoring environmental influences at regular follow-up visits, by questionnaires, serum measurements of infection, and gut microbiome sequencing, we aim to provide the most comprehensive analysis to date of immune system development in newborn children.
Max ERC Funding
1 422 339 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym BrainBIT
Project All-optical brain-to-brain behaviour and information transfer
Researcher (PI) Francesco PAVONE
Host Institution (HI) UNIVERSITA DEGLI STUDI DI FIRENZE
Country Italy
Call Details Advanced Grant (AdG), PE2, ERC-2015-AdG
Summary Exchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions.
We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour.
To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency.
We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.
Summary
Exchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions.
We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour.
To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency.
We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.
Max ERC Funding
2 370 250 €
Duration
Start date: 2016-12-01, End date: 2022-05-31
Project acronym CAVE
Project Challenges and Advancements in Virtual Elements
Researcher (PI) Lourenco Beirao da veiga
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Country Italy
Call Details Consolidator Grant (CoG), PE1, ERC-2015-CoG
Summary The Virtual Element Method (VEM) is a novel technology for the discretization of partial differential equations (PDEs), that shares the same variational background as the Finite Element Method. First but not only, the VEM responds to the strongly increasing interest in using general polyhedral and polygonal meshes in the approximation of PDEs without the limit of using tetrahedral or hexahedral grids. By avoiding the explicit integration of the shape functions that span the discrete space and introducing an innovative construction of the stiffness matrixes, the VEM acquires very interesting properties and advantages with respect to more standard Galerkin methods, yet still keeping the same coding complexity. For instance, the VEM easily allows for polygonal/polyhedral meshes (even non-conforming) with non-convex elements and possibly with curved faces; it allows for discrete spaces of arbitrary C^k regularity on unstructured meshes.
The main scope of the project is to address the recent theoretical challenges posed by VEM and to assess whether this promising technology can achieve a breakthrough in applications. First, the theoretical and computational foundations of VEM will be made stronger. A deeper theoretical insight, supported by a wider numerical experience on benchmark problems, will be developed to gain a better understanding of the method's potentials and set the foundations for more applicative purposes. Second, we will focus our attention on two tough and up-to-date problems of practical interest: large deformation elasticity (where VEM can yield a dramatically more efficient handling of material inclusions, meshing of the domain and grid adaptivity, plus a much stronger robustness with respect to large grid distortions) and the cardiac bidomain model (where VEM can lead to a more accurate domain approximation through MRI data, a flexible refinement/de-refinement procedure along the propagation front, to an exact satisfaction of conservation laws).
Summary
The Virtual Element Method (VEM) is a novel technology for the discretization of partial differential equations (PDEs), that shares the same variational background as the Finite Element Method. First but not only, the VEM responds to the strongly increasing interest in using general polyhedral and polygonal meshes in the approximation of PDEs without the limit of using tetrahedral or hexahedral grids. By avoiding the explicit integration of the shape functions that span the discrete space and introducing an innovative construction of the stiffness matrixes, the VEM acquires very interesting properties and advantages with respect to more standard Galerkin methods, yet still keeping the same coding complexity. For instance, the VEM easily allows for polygonal/polyhedral meshes (even non-conforming) with non-convex elements and possibly with curved faces; it allows for discrete spaces of arbitrary C^k regularity on unstructured meshes.
The main scope of the project is to address the recent theoretical challenges posed by VEM and to assess whether this promising technology can achieve a breakthrough in applications. First, the theoretical and computational foundations of VEM will be made stronger. A deeper theoretical insight, supported by a wider numerical experience on benchmark problems, will be developed to gain a better understanding of the method's potentials and set the foundations for more applicative purposes. Second, we will focus our attention on two tough and up-to-date problems of practical interest: large deformation elasticity (where VEM can yield a dramatically more efficient handling of material inclusions, meshing of the domain and grid adaptivity, plus a much stronger robustness with respect to large grid distortions) and the cardiac bidomain model (where VEM can lead to a more accurate domain approximation through MRI data, a flexible refinement/de-refinement procedure along the propagation front, to an exact satisfaction of conservation laws).
Max ERC Funding
980 634 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym CC-TOP
Project Cryosphere-Carbon on Top of the Earth (CC-Top):Decreasing Uncertainties of Thawing Permafrost and Collapsing Methane Hydrates in the Arctic
Researcher (PI) oerjan GUSTAFSSON
Host Institution (HI) STOCKHOLMS UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), PE10, ERC-2015-AdG
Summary The enormous quantities of frozen carbon in the Arctic, held in shallow soils and sediments, act as “capacitors” of the global carbon system. Thawing permafrost (PF) and collapsing methane hydrates are top candidates to cause a net transfer of carbon from land/ocean to the atmosphere this century, yet uncertainties abound.
Our program targets the East Siberian Arctic Ocean (ESAO), the World’s largest shelf sea, as it holds 80% of coastal PF, 80% of subsea PF and 75% of shallow hydrates. Our initial findings (e.g., Science, 2010; Nature, 2012; PNAS; 2013; Nature Geoscience, 2013, 2014) are challenging earlier notions by showing complexities in terrestrial PF-Carbon remobilization and extensive venting of methane from subsea PF/hydrates. The objective of the CC-Top Program is to transform descriptive and data-lean pictures into quantitative understanding of the CC system, to pin down the present and predict future releases from these “Sleeping Giants” of the global carbon system.
The CC-Top program combines unique Arctic field capacities with powerful molecular-isotopic characterization of PF-carbon/methane to break through on:
The “awakening” of terrestrial PF-C pools: CC-Top will employ great pan-arctic rivers as natural integrators and by probing the δ13C/Δ14C and molecular fingerprints, apportion release fluxes of different PF-C pools.
The ESAO subsea cryosphere/methane: CC-Top will use recent spatially-extensive observations, deep sediment cores and gap-filling expeditions to (i) estimate distribution of subsea PF and hydrates; (ii) establish thermal state (thawing rate) of subsea PF-C; (iii) apportion sources of releasing methane btw subsea-PF, shallow hydrates vs seepage from the deep petroleum megapool using source-diagnostic triple-isotope fingerprinting.
Arctic Ocean slope hydrates: CC-Top will investigate sites (discovered by us 2008-2014) of collapsed hydrates venting methane, to characterize geospatial distribution and causes of destabilization.
Summary
The enormous quantities of frozen carbon in the Arctic, held in shallow soils and sediments, act as “capacitors” of the global carbon system. Thawing permafrost (PF) and collapsing methane hydrates are top candidates to cause a net transfer of carbon from land/ocean to the atmosphere this century, yet uncertainties abound.
Our program targets the East Siberian Arctic Ocean (ESAO), the World’s largest shelf sea, as it holds 80% of coastal PF, 80% of subsea PF and 75% of shallow hydrates. Our initial findings (e.g., Science, 2010; Nature, 2012; PNAS; 2013; Nature Geoscience, 2013, 2014) are challenging earlier notions by showing complexities in terrestrial PF-Carbon remobilization and extensive venting of methane from subsea PF/hydrates. The objective of the CC-Top Program is to transform descriptive and data-lean pictures into quantitative understanding of the CC system, to pin down the present and predict future releases from these “Sleeping Giants” of the global carbon system.
The CC-Top program combines unique Arctic field capacities with powerful molecular-isotopic characterization of PF-carbon/methane to break through on:
The “awakening” of terrestrial PF-C pools: CC-Top will employ great pan-arctic rivers as natural integrators and by probing the δ13C/Δ14C and molecular fingerprints, apportion release fluxes of different PF-C pools.
The ESAO subsea cryosphere/methane: CC-Top will use recent spatially-extensive observations, deep sediment cores and gap-filling expeditions to (i) estimate distribution of subsea PF and hydrates; (ii) establish thermal state (thawing rate) of subsea PF-C; (iii) apportion sources of releasing methane btw subsea-PF, shallow hydrates vs seepage from the deep petroleum megapool using source-diagnostic triple-isotope fingerprinting.
Arctic Ocean slope hydrates: CC-Top will investigate sites (discovered by us 2008-2014) of collapsed hydrates venting methane, to characterize geospatial distribution and causes of destabilization.
Max ERC Funding
2 499 756 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym ChemBioAP
Project Elucidation of autophagy using novel chemical probes
Researcher (PI) Yaowen Wu
Host Institution (HI) UMEA UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS1, ERC-2015-STG
Summary The interest on autophagy, an evolutionarily conserved process in eukaryotes, has enormously increased in the last years, since autophagy is involved in many diseases such as cancer and neurodegenerative disorders. Autophagosome formation is the key process in autophagy. Despite extensive work, the model of autophagosome formation is not yet well established. Some important questions on autophagosome biogenesis remain to be elusive, such as where the bona fide marker protein of autophagosome, LC3, is lipidated, how lipidated LC3 functions in autophagosome formation, and how the proteins for LC3 lipidation and delipidation are involved in autophagosome formation. Although genetic approaches have been useful to identify genes involved in autophagy, they are chronic and thereby the dynamics of phenotypic change cannot be followed, making them not suited for study highly dynamic process such as autophagosome formation. Herein, I propose to develop and use novel chemical probes to address these issues. First, I plan to prepare semi-synthetic caged LC3 proteins and apply them to monitor dynamics of autophagosome formation in the cell in order to address those questions on autophagosome formation. The semi-synthetic LC3 proteins are expected to confer a temporal control and to realize manipulation of protein structure, which renders such studies possible. Second, I intend to develop a versatile approach targeting specific endogenous proteins using a reversible chemically induced dimerization (CID) system, termed as “knock on and off” strategy. I plan to use this approach to elucidate the function of two distinct PI3K complexes in autophagosome formation. On one hand, the establishment of novel approaches will open up a new avenue for studying biological processes. On the other hand, the use of the tool will reveal the mechanism of autophagy.
Summary
The interest on autophagy, an evolutionarily conserved process in eukaryotes, has enormously increased in the last years, since autophagy is involved in many diseases such as cancer and neurodegenerative disorders. Autophagosome formation is the key process in autophagy. Despite extensive work, the model of autophagosome formation is not yet well established. Some important questions on autophagosome biogenesis remain to be elusive, such as where the bona fide marker protein of autophagosome, LC3, is lipidated, how lipidated LC3 functions in autophagosome formation, and how the proteins for LC3 lipidation and delipidation are involved in autophagosome formation. Although genetic approaches have been useful to identify genes involved in autophagy, they are chronic and thereby the dynamics of phenotypic change cannot be followed, making them not suited for study highly dynamic process such as autophagosome formation. Herein, I propose to develop and use novel chemical probes to address these issues. First, I plan to prepare semi-synthetic caged LC3 proteins and apply them to monitor dynamics of autophagosome formation in the cell in order to address those questions on autophagosome formation. The semi-synthetic LC3 proteins are expected to confer a temporal control and to realize manipulation of protein structure, which renders such studies possible. Second, I intend to develop a versatile approach targeting specific endogenous proteins using a reversible chemically induced dimerization (CID) system, termed as “knock on and off” strategy. I plan to use this approach to elucidate the function of two distinct PI3K complexes in autophagosome formation. On one hand, the establishment of novel approaches will open up a new avenue for studying biological processes. On the other hand, the use of the tool will reveal the mechanism of autophagy.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-09-01, End date: 2021-08-31