Project acronym ActiveWindFarms
Project Active Wind Farms: Optimization and Control of Atmospheric Energy Extraction in Gigawatt Wind Farms
Researcher (PI) Johan Meyers
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary With the recognition that wind energy will become an important contributor to the world’s energy portfolio, several wind farms with a capacity of over 1 gigawatt are in planning phase. In the past, engineering of wind farms focused on a bottom-up approach, in which atmospheric wind availability was considered to be fixed by climate and weather. However, farms of gigawatt size slow down the Atmospheric Boundary Layer (ABL) as a whole, reducing the availability of wind at turbine hub height. In Denmark’s large off-shore farms, this leads to underperformance of turbines which can reach levels of 40%–50% compared to the same turbine in a lone-standing case. For large wind farms, the vertical structure and turbulence physics of the flow in the ABL become crucial ingredients in their design and operation. This introduces a new set of scientific challenges related to the design and control of large wind farms. The major ambition of the present research proposal is to employ optimal control techniques to control the interaction between large wind farms and the ABL, and optimize overall farm-power extraction. Individual turbines are used as flow actuators by dynamically pitching their blades using time scales ranging between 10 to 500 seconds. The application of such control efforts on the atmospheric boundary layer has never been attempted before, and introduces flow control on a physical scale which is currently unprecedented. The PI possesses a unique combination of expertise and tools enabling these developments: efficient parallel large-eddy simulations of wind farms, multi-scale turbine modeling, and gradient-based optimization in large optimization-parameter spaces using adjoint formulations. To ensure a maximum impact on the wind-engineering field, the project aims at optimal control, experimental wind-tunnel validation, and at including multi-disciplinary aspects, related to structural mechanics, power quality, and controller design.
Summary
With the recognition that wind energy will become an important contributor to the world’s energy portfolio, several wind farms with a capacity of over 1 gigawatt are in planning phase. In the past, engineering of wind farms focused on a bottom-up approach, in which atmospheric wind availability was considered to be fixed by climate and weather. However, farms of gigawatt size slow down the Atmospheric Boundary Layer (ABL) as a whole, reducing the availability of wind at turbine hub height. In Denmark’s large off-shore farms, this leads to underperformance of turbines which can reach levels of 40%–50% compared to the same turbine in a lone-standing case. For large wind farms, the vertical structure and turbulence physics of the flow in the ABL become crucial ingredients in their design and operation. This introduces a new set of scientific challenges related to the design and control of large wind farms. The major ambition of the present research proposal is to employ optimal control techniques to control the interaction between large wind farms and the ABL, and optimize overall farm-power extraction. Individual turbines are used as flow actuators by dynamically pitching their blades using time scales ranging between 10 to 500 seconds. The application of such control efforts on the atmospheric boundary layer has never been attempted before, and introduces flow control on a physical scale which is currently unprecedented. The PI possesses a unique combination of expertise and tools enabling these developments: efficient parallel large-eddy simulations of wind farms, multi-scale turbine modeling, and gradient-based optimization in large optimization-parameter spaces using adjoint formulations. To ensure a maximum impact on the wind-engineering field, the project aims at optimal control, experimental wind-tunnel validation, and at including multi-disciplinary aspects, related to structural mechanics, power quality, and controller design.
Max ERC Funding
1 499 241 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym BRAVE
Project "Bicuspid Related Aortopathy, a Vibrant Exploration"
Researcher (PI) Bart Leo Loeys
Host Institution (HI) UNIVERSITEIT ANTWERPEN
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary "Bicuspid aortic valve, a heart valve with only two leaflets instead of three, is the most common congenital heart defect with an estimated prevalence of about 1-2%. The heart defect often remains asymptomatic but in at least 10% of the bicuspid aortic valve patients, an ascending aortic aneurysm develops as well. If not detected in a timely fashion, this can lead to an aortic aneurysm dissection with a high mortality. In view of the prevalent nature of this heart defect, this implies an important health care problem. Historically, it was always hypothesized that abnormal blood flow across the bicuspid aortic valve led to aneurysm formation. However in recent years, the importance of a genetic contribution has been suggested based on the high heritability and it is currently believed that the same genetic factors predispose to the developmental valve defect and the aortic aneurysm formation. The inheritance pattern is most consistent with an autosomal dominant disorder with variable penetrance and expressivity. Until now, the latter have significantly hampered the causal gene identification but the era of next generation sequencing is now offering unprecedented opportunities for a major breakthrough in this area.
Through detailed signalling pathway analysis, miRNA profiling and next generation sequencing, this project will contribute significantly to resolving the genetic causes of bicuspid related aortopathy, provide critical knowledge on the pathogenesis of aortic aneurysmal disease and deliver a mouse model for future therapeutical trials."
Summary
"Bicuspid aortic valve, a heart valve with only two leaflets instead of three, is the most common congenital heart defect with an estimated prevalence of about 1-2%. The heart defect often remains asymptomatic but in at least 10% of the bicuspid aortic valve patients, an ascending aortic aneurysm develops as well. If not detected in a timely fashion, this can lead to an aortic aneurysm dissection with a high mortality. In view of the prevalent nature of this heart defect, this implies an important health care problem. Historically, it was always hypothesized that abnormal blood flow across the bicuspid aortic valve led to aneurysm formation. However in recent years, the importance of a genetic contribution has been suggested based on the high heritability and it is currently believed that the same genetic factors predispose to the developmental valve defect and the aortic aneurysm formation. The inheritance pattern is most consistent with an autosomal dominant disorder with variable penetrance and expressivity. Until now, the latter have significantly hampered the causal gene identification but the era of next generation sequencing is now offering unprecedented opportunities for a major breakthrough in this area.
Through detailed signalling pathway analysis, miRNA profiling and next generation sequencing, this project will contribute significantly to resolving the genetic causes of bicuspid related aortopathy, provide critical knowledge on the pathogenesis of aortic aneurysmal disease and deliver a mouse model for future therapeutical trials."
Max ERC Funding
1 497 895 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym DAMONA
Project Mutation and Recombination in the Cattle Germline: Genomic Analysis and Impact on Fertility
Researcher (PI) Michel Alphonse Julien Georges
Host Institution (HI) UNIVERSITE DE LIEGE
Call Details Advanced Grant (AdG), LS2, ERC-2012-ADG_20120314
Summary "Mutation and recombination are fundamental biological processes that determine adaptability of populations. The mutation rate reflects the equilibrium between the need to adapt, the burden of mutation load, the “cost of fidelity”, and random drift that determines a lower limit in achievable fidelity. Recombination fulfills an essential mechanistic role during meiosis, ensuring proper chromosomal segregation. Recombination affects the rate of creation and loss of favorable haplotypes, imposing 2nd-order selection pressure on modifiers of recombination.
It is becoming apparent that recombination and mutation rates vary between individuals, and that these differences are in part inherited. Both processes are therefore “evolvable”, and amenable to genomic analysis. Identifying genetic determinants underlying these differences will provide insights in the regulation of mutation and recombination. The mutational load, and in particular the number of lethal equivalents per individual, remains poorly defined as epidemiological and molecular data yield estimates that differ by one order of magnitude. A relationship between recombination and fertility has been reported in women but awaits confirmation.
Population structure (small effective population size; large harems), phenotypic data collection (systematic recording of > 50 traits on millions of cows), and large-scale SNP genotyping (for genomic selection), make cattle populations uniquely suited for genetic analysis. DAMONA proposes to exploit these unique resources, combined with recent advances in next generation sequencing and genotyping, to:
(i) quantify and characterize inter-individual variation in male and female mutation and recombination rates,
(ii) map, fine-map and identify causative genes underlying QTL for these four phenotypes,
(iii) test the effect of loss-of-function variants on >50 traits including fertility, and
(iv) study the effect of variation in recombination on fertility."
Summary
"Mutation and recombination are fundamental biological processes that determine adaptability of populations. The mutation rate reflects the equilibrium between the need to adapt, the burden of mutation load, the “cost of fidelity”, and random drift that determines a lower limit in achievable fidelity. Recombination fulfills an essential mechanistic role during meiosis, ensuring proper chromosomal segregation. Recombination affects the rate of creation and loss of favorable haplotypes, imposing 2nd-order selection pressure on modifiers of recombination.
It is becoming apparent that recombination and mutation rates vary between individuals, and that these differences are in part inherited. Both processes are therefore “evolvable”, and amenable to genomic analysis. Identifying genetic determinants underlying these differences will provide insights in the regulation of mutation and recombination. The mutational load, and in particular the number of lethal equivalents per individual, remains poorly defined as epidemiological and molecular data yield estimates that differ by one order of magnitude. A relationship between recombination and fertility has been reported in women but awaits confirmation.
Population structure (small effective population size; large harems), phenotypic data collection (systematic recording of > 50 traits on millions of cows), and large-scale SNP genotyping (for genomic selection), make cattle populations uniquely suited for genetic analysis. DAMONA proposes to exploit these unique resources, combined with recent advances in next generation sequencing and genotyping, to:
(i) quantify and characterize inter-individual variation in male and female mutation and recombination rates,
(ii) map, fine-map and identify causative genes underlying QTL for these four phenotypes,
(iii) test the effect of loss-of-function variants on >50 traits including fertility, and
(iv) study the effect of variation in recombination on fertility."
Max ERC Funding
2 258 000 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym DelCancer
Project The role of loss-of-heterozygosity in cancer development and progression
Researcher (PI) Anna Sablina
Host Institution (HI) VIB
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary Somatically acquired loss-of-heterozygosity (LOH) is extremely common in cancer; deletions of recessive cancer genes, miRNAs, and regulatory elements, can confer selective growth advantage, whereas deletions over fragile sites are thought to reflect an increased local rate of DNA breakage. However, most LOHs in cancer genomes remain unexplained. Here we plan to combine a TALEN technology and the experimental models of cell transformation derived from primary human cells to delete specific chromosomal regions that are frequently lost in cancer samples. The development of novel strategies to introduce large chromosomal rearrangements into the genome of primary human cells will offer new perspectives for studying gene function, for elucidating chromosomal organisation, and for increasing our understanding of the molecular mechanisms and pathways underlying cancer development.Using this technology to genetically engineer cells that model cancer-associated genetic alterations, we will identify LOH regions critical for the development and progression of human cancers, and will investigate the cooperative effect of loss of genes, non-coding RNAs, and regulatory elements located within the deleted regions on cancer-associated phenotypes. We will assess how disruption of the three-dimensional chromosomal network in cells with specific chromosomal deletions contributes to cell transformation. Isogenic cell lines harbouring targeted chromosomal alterations will also serve us as a platform to identify compounds with specificity for particular genetic abnormalities. As a next step, we plan to unravel the mechanisms by which particular homozygous deletions contribute to cancer-associated phenotypes. If successful, the results of these studies will represent an important step towards understanding oncogenesis, and could yield new diagnostic and prognostic markers as well as identify potential therapeutic targets.
Summary
Somatically acquired loss-of-heterozygosity (LOH) is extremely common in cancer; deletions of recessive cancer genes, miRNAs, and regulatory elements, can confer selective growth advantage, whereas deletions over fragile sites are thought to reflect an increased local rate of DNA breakage. However, most LOHs in cancer genomes remain unexplained. Here we plan to combine a TALEN technology and the experimental models of cell transformation derived from primary human cells to delete specific chromosomal regions that are frequently lost in cancer samples. The development of novel strategies to introduce large chromosomal rearrangements into the genome of primary human cells will offer new perspectives for studying gene function, for elucidating chromosomal organisation, and for increasing our understanding of the molecular mechanisms and pathways underlying cancer development.Using this technology to genetically engineer cells that model cancer-associated genetic alterations, we will identify LOH regions critical for the development and progression of human cancers, and will investigate the cooperative effect of loss of genes, non-coding RNAs, and regulatory elements located within the deleted regions on cancer-associated phenotypes. We will assess how disruption of the three-dimensional chromosomal network in cells with specific chromosomal deletions contributes to cell transformation. Isogenic cell lines harbouring targeted chromosomal alterations will also serve us as a platform to identify compounds with specificity for particular genetic abnormalities. As a next step, we plan to unravel the mechanisms by which particular homozygous deletions contribute to cancer-associated phenotypes. If successful, the results of these studies will represent an important step towards understanding oncogenesis, and could yield new diagnostic and prognostic markers as well as identify potential therapeutic targets.
Max ERC Funding
1 498 764 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym DIVISIONPLANESWITCH
Project Control mechanisms that pattern microtubules for switching cell division planes during plant morphogenesis
Researcher (PI) Pankaj Bacharam Dhonukshe
Host Institution (HI) VIB
Call Details Starting Grant (StG), LS3, ERC-2012-StG_20111109
Summary Oriented cell divisions dictate morphogenesis by shaping tissues and organs of multicellular organisms. Oriented cell divisions have profound influence in plants because their cell positions are locked by shared cell walls. A relay of cell divisions involving precise division plane switches determines embryonic body plan, organ layout and organ architecture in plants. Cell division planes in plants are specified by reorganization of premitotic cortical microtubule array and how this occurs is a long-standing key question.
My recent results establish, for the first time in plants, an in vivo inducible and traceable, precise 90º cell division plane switch system. With this system I identified a pathway that proceeds from transcriptional activation through a signaling module all the way to the activation of microtubule regulators that orchestrate switches in premitotic microtubule organization and cell division planes. My findings provide a first paradigm in plants of how genetic circuitry patterns cell division planes via feeding onto cellular machinery and pave the way for unraveling mechanistic control of cell division plane switch.
By establishing a precise cell division plane switch system I am in a unique position to answer:
1. What transcriptional program and molecular players control premitotic microtubule reorganization?
2. Which mechanisms switch premitotic microtubule array?
3. What influence do identified players and mechanisms have on different types of oriented cell divisions in plants?
For this I propose a systematic research plan combining (i) forward genetics and expression profile screens for identifying a suite of microtubule regulators, (ii) state-of-the-art microscopy and modeling approaches for uncovering mechanisms of their actions and (iii) their tissue-specific manipulations to modify plant form.
By unraveling players and mechanisms this proposal shall resolve regulation of oriented cell divisions and expand plant engineering toolbox.
Summary
Oriented cell divisions dictate morphogenesis by shaping tissues and organs of multicellular organisms. Oriented cell divisions have profound influence in plants because their cell positions are locked by shared cell walls. A relay of cell divisions involving precise division plane switches determines embryonic body plan, organ layout and organ architecture in plants. Cell division planes in plants are specified by reorganization of premitotic cortical microtubule array and how this occurs is a long-standing key question.
My recent results establish, for the first time in plants, an in vivo inducible and traceable, precise 90º cell division plane switch system. With this system I identified a pathway that proceeds from transcriptional activation through a signaling module all the way to the activation of microtubule regulators that orchestrate switches in premitotic microtubule organization and cell division planes. My findings provide a first paradigm in plants of how genetic circuitry patterns cell division planes via feeding onto cellular machinery and pave the way for unraveling mechanistic control of cell division plane switch.
By establishing a precise cell division plane switch system I am in a unique position to answer:
1. What transcriptional program and molecular players control premitotic microtubule reorganization?
2. Which mechanisms switch premitotic microtubule array?
3. What influence do identified players and mechanisms have on different types of oriented cell divisions in plants?
For this I propose a systematic research plan combining (i) forward genetics and expression profile screens for identifying a suite of microtubule regulators, (ii) state-of-the-art microscopy and modeling approaches for uncovering mechanisms of their actions and (iii) their tissue-specific manipulations to modify plant form.
By unraveling players and mechanisms this proposal shall resolve regulation of oriented cell divisions and expand plant engineering toolbox.
Max ERC Funding
1 500 000 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym DOUBLE-UP
Project The importance of gene and genome duplications for natural and artificial organism populations
Researcher (PI) Yves Eddy Philomena Van De Peer
Host Institution (HI) VIB
Call Details Advanced Grant (AdG), LS2, ERC-2012-ADG_20120314
Summary The long-term establishment of ancient organisms that have undergone whole genome duplications has been exceedingly rare. On the other hand, tens of thousands of now-living species are polyploid and contain multiple copies of their genome. The paucity of ancient genome duplications and the existence of so many species that are currently polyploid provide an interesting and fascinating enigma. A question that remains is whether these older genome duplications have survived by coincidence or because they did occur at very specific times, for instance during major ecological upheavals and periods of extinction. It has indeed been proposed that chromosome doubling conveys greater stress tolerance by fostering slower development, delayed reproduction and longer life span. Furthermore, polyploids have also been considered to have greater ability to colonize new or disturbed habitats. If polyploidy allowed many plant lineages to survive and adapt during global changes, as suggested, we might wonder whether polyploidy will confer a similar advantage in the current period of global warming and general ecological pressure caused by the human race. Given predictions that species extinction is now occurring at as high rates as during previous mass extinctions, will the presumed extra adaptability of polyploid plants mean they will become the dominant species? In the current proposal, we hope to address these questions at different levels through 1) the analysis of whole plant genome sequence data and 2) the in silico modelling of artificial gene regulatory networks to mimic the genomic consequences of genome doubling and how this may affect network structure and dosage balance. Furthermore, we aim at using simulated robotic models running on artificial gene regulatory networks in complex environments to evaluate how both natural and artificial organism populations can potentially benefit from gene and genome duplications for adaptation, survival, and evolution in general.
Summary
The long-term establishment of ancient organisms that have undergone whole genome duplications has been exceedingly rare. On the other hand, tens of thousands of now-living species are polyploid and contain multiple copies of their genome. The paucity of ancient genome duplications and the existence of so many species that are currently polyploid provide an interesting and fascinating enigma. A question that remains is whether these older genome duplications have survived by coincidence or because they did occur at very specific times, for instance during major ecological upheavals and periods of extinction. It has indeed been proposed that chromosome doubling conveys greater stress tolerance by fostering slower development, delayed reproduction and longer life span. Furthermore, polyploids have also been considered to have greater ability to colonize new or disturbed habitats. If polyploidy allowed many plant lineages to survive and adapt during global changes, as suggested, we might wonder whether polyploidy will confer a similar advantage in the current period of global warming and general ecological pressure caused by the human race. Given predictions that species extinction is now occurring at as high rates as during previous mass extinctions, will the presumed extra adaptability of polyploid plants mean they will become the dominant species? In the current proposal, we hope to address these questions at different levels through 1) the analysis of whole plant genome sequence data and 2) the in silico modelling of artificial gene regulatory networks to mimic the genomic consequences of genome doubling and how this may affect network structure and dosage balance. Furthermore, we aim at using simulated robotic models running on artificial gene regulatory networks in complex environments to evaluate how both natural and artificial organism populations can potentially benefit from gene and genome duplications for adaptation, survival, and evolution in general.
Max ERC Funding
2 217 525 €
Duration
Start date: 2013-10-01, End date: 2018-09-30
Project acronym ELECTROTALK
Project Starting an electrical conversation between microorganisms and electrodes to achieve bioproduction
Researcher (PI) Korneel Pieter Herman Leo Ann Rabaey
Host Institution (HI) UNIVERSITEIT GENT
Call Details Starting Grant (StG), LS9, ERC-2012-StG_20111109
Summary "Electrochemically active bacteria enable a host of novel processes in bioproduction, bioenergy and bioremediation. Key to the success of these processes is effective adherence of the bacterial cells to an electrode surface and subsequent equally effective electron exchange with the electrode. While the cellular mechanisms for electron transfer are increasingly known, what drives bacterial adsorption and desorption to positively or negatively polarized electrodes is largely unknown. Particularly processes driven by cathodes tend to be slow, and suffer from limited microbial adherence and lack of growth of the microorganisms. ELECTROTALK aims at developing a mechanistic understanding of mobility towards and microbial adherence at surfaces, from single cell level to complete biofilm formation. Based on this knowledge, effectively catalyzed bio-electrodes will be developed for novel bioproduction processes. Such bioproduction processes, termed microbial electrosynthesis, are independent of arable land availability, promise high production densities and enable the capture of CO2 or more efficient resource-usage for a range of products. Understanding the nature of the microorganism-electrode interaction will create a window of opportunity to improve this process and achieve effective bioproduction. Moreover, as the electrical interaction directly relates to microbial activity electrodes may serve as a means to start up a conversation with the cells. To achieve our aims we will: (i) select and characterize biocatalysts both as pure cultures and microbial communities; (ii) investigate cell adherence and electron transfer in function of electrode topography and chemistry as well as under different operational conditions; (iii) develop an electrode-microorganism combination achieving effective electron transfer; and (iv) electrochemically construct biofilms with defined structure or stratification."
Summary
"Electrochemically active bacteria enable a host of novel processes in bioproduction, bioenergy and bioremediation. Key to the success of these processes is effective adherence of the bacterial cells to an electrode surface and subsequent equally effective electron exchange with the electrode. While the cellular mechanisms for electron transfer are increasingly known, what drives bacterial adsorption and desorption to positively or negatively polarized electrodes is largely unknown. Particularly processes driven by cathodes tend to be slow, and suffer from limited microbial adherence and lack of growth of the microorganisms. ELECTROTALK aims at developing a mechanistic understanding of mobility towards and microbial adherence at surfaces, from single cell level to complete biofilm formation. Based on this knowledge, effectively catalyzed bio-electrodes will be developed for novel bioproduction processes. Such bioproduction processes, termed microbial electrosynthesis, are independent of arable land availability, promise high production densities and enable the capture of CO2 or more efficient resource-usage for a range of products. Understanding the nature of the microorganism-electrode interaction will create a window of opportunity to improve this process and achieve effective bioproduction. Moreover, as the electrical interaction directly relates to microbial activity electrodes may serve as a means to start up a conversation with the cells. To achieve our aims we will: (i) select and characterize biocatalysts both as pure cultures and microbial communities; (ii) investigate cell adherence and electron transfer in function of electrode topography and chemistry as well as under different operational conditions; (iii) develop an electrode-microorganism combination achieving effective electron transfer; and (iv) electrochemically construct biofilms with defined structure or stratification."
Max ERC Funding
1 494 126 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym MAtrix
Project In silico and in vitro Models of Angiogenesis: unravelling the role of the extracellular matrix
Researcher (PI) Hans Pol S Van Oosterwyck
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary Angiogenesis, the formation of new blood vessels from the existing vasculature, is a process that is fundamental to normal tissue growth, wound repair and disease. The control of angiogenesis is of utmost importance for tissue regenerative therapies as well as cancer treatment, however this remains a challenge. The extracellular matrix (ECM) is a one of the key controlling factors of angiogenesis. The mechanisms through which the ECM exerts its influence are poorly understood. MAtrix will create unprecedented opportunities for unraveling the role of the ECM in angiogenesis. It will do so by creating a highly innovative, multiscale in silico model that provides quantitative, subcellular resolution on cell-matrix interaction, which is key to the understanding of cell migration. In this way, MAtrix goes substantially beyond the state of the art in terms of computational models of angiogenesis. It will integrate mechanisms of ECM-mediated cell migration and relate them to intracellular regulatory mechanisms of angiogenesis.
Apart from its innovation in terms of computational modelling, MAtrix’ impact is related to its interdisciplinarity, involving computer simulations and in vitro experiments. This will enable to investigate research hypotheses on the role of the ECM in angiogenesis that are generated by the in silico model. State of the art technologies (fluorescence microscopy, cell and ECM mechanics, biomaterials design) will be applied –in conjunction with the in silico model- to quantity cell-ECM mechanical interaction at a subcellular level and the dynamics of cell migration. In vitro experiments will be performed for a broad range of biomaterials and their characteristics. In this way, MAtrix will deliver a proof-of-concept that an in silico model can help in identifying and prioritising biomaterials characteristics, relevant for angiogenesis. MAtrix’ findings can have a major impact on the development of therapies that want to control the angiogenic response.
Summary
Angiogenesis, the formation of new blood vessels from the existing vasculature, is a process that is fundamental to normal tissue growth, wound repair and disease. The control of angiogenesis is of utmost importance for tissue regenerative therapies as well as cancer treatment, however this remains a challenge. The extracellular matrix (ECM) is a one of the key controlling factors of angiogenesis. The mechanisms through which the ECM exerts its influence are poorly understood. MAtrix will create unprecedented opportunities for unraveling the role of the ECM in angiogenesis. It will do so by creating a highly innovative, multiscale in silico model that provides quantitative, subcellular resolution on cell-matrix interaction, which is key to the understanding of cell migration. In this way, MAtrix goes substantially beyond the state of the art in terms of computational models of angiogenesis. It will integrate mechanisms of ECM-mediated cell migration and relate them to intracellular regulatory mechanisms of angiogenesis.
Apart from its innovation in terms of computational modelling, MAtrix’ impact is related to its interdisciplinarity, involving computer simulations and in vitro experiments. This will enable to investigate research hypotheses on the role of the ECM in angiogenesis that are generated by the in silico model. State of the art technologies (fluorescence microscopy, cell and ECM mechanics, biomaterials design) will be applied –in conjunction with the in silico model- to quantity cell-ECM mechanical interaction at a subcellular level and the dynamics of cell migration. In vitro experiments will be performed for a broad range of biomaterials and their characteristics. In this way, MAtrix will deliver a proof-of-concept that an in silico model can help in identifying and prioritising biomaterials characteristics, relevant for angiogenesis. MAtrix’ findings can have a major impact on the development of therapies that want to control the angiogenic response.
Max ERC Funding
1 497 400 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym NOVIB
Project The Nonlinear Tuned Vibration Absorber
Researcher (PI) Gaetan Kerschen
Host Institution (HI) UNIVERSITE DE LIEGE
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary "Even after more than one century of flight, both civil and military aircraft are still plagued by major vibration problems. A well-known example is the external-store induced flutter of the F-16 fighter aircraft. Such dynamical phenomena, commonly known as aeroelastic instabilities, result from the transfer of energy from the free stream to the structure and can lead to limit cycle oscillations, a phenomenon with no linear counterpart. Since nonlinear dynamical systems theory is not yet mature, the inherently nonlinear nature of these oscillations renders their mitigation a particularly difficult problem. The only practical solution to date is to limit aircraft flight envelope to regions where these instabilities are not expected to occur, as verified by intensive and expensive flight campaigns. This limitation results in a severe decrease in both aircraft efficiency and performance.
At the heart of this project is a fundamental change in paradigm: although nonlinearity is usually seen as an enemy, I propose to control - and even suppress - aeroelastic instability through the intentional use of nonlinearity. This approach has the potential to bring about a major change in aircraft design and will be achieved thanks to the development of the nonlinear tuned vibration absorber, a new, rigorous nonlinear counterpart of the linear tuned vibration absorber. This work represents a number of significant challenges, because the novel functionalities brought by the intentional use of nonlinearity can be accompanied by adverse nonlinear dynamical effects. The successful mitigation of these unwanted nonlinear effects will be a major objective of our proposed research; it will require achieving both theoretical and technical advances to make it possible. A specific effort will be made to demonstrate experimentally the theoretical findings of this research with extensive wind tunnel testing and practical implementation of the nonlinear tuned vibration absorber.
Finally, nonlinear instabilities such as limit cycle oscillations can be found in a number of non-aircraft applications including in bridges, automotive disc brakes and machine tools. The nonlinear tuned vibration absorber could also find uses in resolving problems in these applications, thus ensuring the generic character of the project."
Summary
"Even after more than one century of flight, both civil and military aircraft are still plagued by major vibration problems. A well-known example is the external-store induced flutter of the F-16 fighter aircraft. Such dynamical phenomena, commonly known as aeroelastic instabilities, result from the transfer of energy from the free stream to the structure and can lead to limit cycle oscillations, a phenomenon with no linear counterpart. Since nonlinear dynamical systems theory is not yet mature, the inherently nonlinear nature of these oscillations renders their mitigation a particularly difficult problem. The only practical solution to date is to limit aircraft flight envelope to regions where these instabilities are not expected to occur, as verified by intensive and expensive flight campaigns. This limitation results in a severe decrease in both aircraft efficiency and performance.
At the heart of this project is a fundamental change in paradigm: although nonlinearity is usually seen as an enemy, I propose to control - and even suppress - aeroelastic instability through the intentional use of nonlinearity. This approach has the potential to bring about a major change in aircraft design and will be achieved thanks to the development of the nonlinear tuned vibration absorber, a new, rigorous nonlinear counterpart of the linear tuned vibration absorber. This work represents a number of significant challenges, because the novel functionalities brought by the intentional use of nonlinearity can be accompanied by adverse nonlinear dynamical effects. The successful mitigation of these unwanted nonlinear effects will be a major objective of our proposed research; it will require achieving both theoretical and technical advances to make it possible. A specific effort will be made to demonstrate experimentally the theoretical findings of this research with extensive wind tunnel testing and practical implementation of the nonlinear tuned vibration absorber.
Finally, nonlinear instabilities such as limit cycle oscillations can be found in a number of non-aircraft applications including in bridges, automotive disc brakes and machine tools. The nonlinear tuned vibration absorber could also find uses in resolving problems in these applications, thus ensuring the generic character of the project."
Max ERC Funding
1 316 440 €
Duration
Start date: 2012-09-01, End date: 2017-08-31
Project acronym OxyMO
Project Oxygen sensing in macrophages: implications for cancer and ischemia
Researcher (PI) Massimiliano Mazzone
Host Institution (HI) VIB
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary Macrophages exist in distinct differentiation states. Proangiogenic/immunosuppressive (M2-like) macrophages and antitumoral/proinflammatory (M1-like) macrophages represent two extremities of a continuum. Because lineage-defined subsets have not been identified yet, macrophage heterogeneity is likely to reflect the plasticity of these cells in response to microenvironmental signals. The concept that hypoxia can induce inflammation has gained general acceptance. However, little is known on how extravasated monocytes and their macrophage progeny react to a condition of low oxygen. Different macrophage phenotypes have been positively and negatively associated with the clinical outcome of vascular disorders as cancer and ischemia. These pathological conditions are characterized not only by dysfunctional vessels, which impair oxygenation, but also by strong immunoregulatory responses. Recently we have shown that reduced activity of the oxygen sensor PHD2 in macrophages skews their polarization towards a proarteriogenic (M2-like) phenotype, which confers protection against ischemia. Based on these findings, we propose to dissect upstream and downstream signals to the oxygen sensing machinery and hypoxia-response in macrophages. By using a genome-wide transcriptional profiling approach and a high-throughput interactome analysis, combined with mouse genetic tools, we will identify the gene signature of macrophages in hypoxia and unravel the molecular executors of this response. The identification of the effectors responsible for macrophage skewing in relation to oxygen availability will contribute to a better understanding of immunoregulatory cues during disease progression and unveil the multifaceted function of macrophages during vessel formation. With the focus of our research on macrophage manipulation towards a desired phenotype, we will offer new treatment options for cancer and ischemia that might result in optimized therapies and overcome resistance to current drugs.
Summary
Macrophages exist in distinct differentiation states. Proangiogenic/immunosuppressive (M2-like) macrophages and antitumoral/proinflammatory (M1-like) macrophages represent two extremities of a continuum. Because lineage-defined subsets have not been identified yet, macrophage heterogeneity is likely to reflect the plasticity of these cells in response to microenvironmental signals. The concept that hypoxia can induce inflammation has gained general acceptance. However, little is known on how extravasated monocytes and their macrophage progeny react to a condition of low oxygen. Different macrophage phenotypes have been positively and negatively associated with the clinical outcome of vascular disorders as cancer and ischemia. These pathological conditions are characterized not only by dysfunctional vessels, which impair oxygenation, but also by strong immunoregulatory responses. Recently we have shown that reduced activity of the oxygen sensor PHD2 in macrophages skews their polarization towards a proarteriogenic (M2-like) phenotype, which confers protection against ischemia. Based on these findings, we propose to dissect upstream and downstream signals to the oxygen sensing machinery and hypoxia-response in macrophages. By using a genome-wide transcriptional profiling approach and a high-throughput interactome analysis, combined with mouse genetic tools, we will identify the gene signature of macrophages in hypoxia and unravel the molecular executors of this response. The identification of the effectors responsible for macrophage skewing in relation to oxygen availability will contribute to a better understanding of immunoregulatory cues during disease progression and unveil the multifaceted function of macrophages during vessel formation. With the focus of our research on macrophage manipulation towards a desired phenotype, we will offer new treatment options for cancer and ischemia that might result in optimized therapies and overcome resistance to current drugs.
Max ERC Funding
1 499 306 €
Duration
Start date: 2012-11-01, End date: 2017-10-31