Project acronym BHIVE
Project Bio-derived HIgh Value polymers through novel Enzyme function
Researcher (PI) Emma Rusi Master
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Call Details Consolidator Grant (CoG), LS9, ERC-2014-CoG
Summary Recent advances in systems-level study of cells and organisms have revealed the enormous potential to live more sustainably through better use of biological processes. Plants sustainably synthesize the most abundant and diverse materials on Earth. By applying recent advances in life science technology, we can better harness renewable plant resources and bioconversion processes, to develop environmentally and politically sustainable human enterprise and lifestyles. At the same time, the global market for high-value biochemicals and bioplastics from forest and agricultural sources is rapidly increasing, which presents new opportunities for forest and agricultural sectors.
The overall aim of BHIVE is to illuminate uncharted regions of genome and metagenome sequences to discover entirely new protein families that can be used to sustainably synthesize novel, high-value biomaterials from renewable plant resources. The approach will include three parallel research thrusts: 1) strategic analysis of transcriptome and metagenome sequences to identify proteins with entirely unknown function relevant to biomass (lignocellulose) transformation, 2) mapping of uncharted regions within phylogenetic trees of poorly characterized enzyme families with recognized potential to modify the chemistry and biophysical properties of plant polysaccharides, and 3) the design and development of novel enzyme screens to directly address the increasing limitations of existing assays to uncover entirely new protein functions. BHIVE will be unique in its undivided focus on characterizing lignocellulose-active proteins encoded by the 30-40% of un-annotated sequence, or genomic “dark matter”, typical of nearly all genome sequences. In this way, BHIVE tackles a key constraint to fully realizing the societal and environmental benefits of the genomics era.
Summary
Recent advances in systems-level study of cells and organisms have revealed the enormous potential to live more sustainably through better use of biological processes. Plants sustainably synthesize the most abundant and diverse materials on Earth. By applying recent advances in life science technology, we can better harness renewable plant resources and bioconversion processes, to develop environmentally and politically sustainable human enterprise and lifestyles. At the same time, the global market for high-value biochemicals and bioplastics from forest and agricultural sources is rapidly increasing, which presents new opportunities for forest and agricultural sectors.
The overall aim of BHIVE is to illuminate uncharted regions of genome and metagenome sequences to discover entirely new protein families that can be used to sustainably synthesize novel, high-value biomaterials from renewable plant resources. The approach will include three parallel research thrusts: 1) strategic analysis of transcriptome and metagenome sequences to identify proteins with entirely unknown function relevant to biomass (lignocellulose) transformation, 2) mapping of uncharted regions within phylogenetic trees of poorly characterized enzyme families with recognized potential to modify the chemistry and biophysical properties of plant polysaccharides, and 3) the design and development of novel enzyme screens to directly address the increasing limitations of existing assays to uncover entirely new protein functions. BHIVE will be unique in its undivided focus on characterizing lignocellulose-active proteins encoded by the 30-40% of un-annotated sequence, or genomic “dark matter”, typical of nearly all genome sequences. In this way, BHIVE tackles a key constraint to fully realizing the societal and environmental benefits of the genomics era.
Max ERC Funding
1 977 781 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym BIZEB
Project Bio-Imaging of Zoonotic and Emerging Bunyaviruses
Researcher (PI) Juha Huiskonen
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Consolidator Grant (CoG), LS1, ERC-2014-CoG
Summary We aim to understand host cell entry of enveloped viruses at molecular level. A crucial step in this process is when the viral membrane fuses with the cell membrane. Similarly to cell–cell fusion, this step is mediated by fusion proteins (classes I–III). Several medically important viruses, notably dengue and many bunyaviruses, harbour a class II fusion protein. Class II fusion protein structures have been solved in pre- and post-fusion conformation and in some cases different factors promoting fusion have been determined. However, questions about the most important steps of this key process remain unanswered. I will focus on the entry mechanism of bunyaviruses by using cutting-edge, high spatial and temporal resolution bio-imaging techniques. These viruses have been chosen as a model system to maximise the significance of the project: they form an emerging viral threat to humans and animals, no approved vaccines or antivirals exist for human use and they are less studied than other class II fusion protein systems. Cryo-electron microscopy and tomography will be used to solve high-resolution structures (up to ~3 Å) of viruses, in addition to virus–receptor and virus–membrane complexes. Advanced fluorescence microscopy techniques will be used to probe the dynamics of virus entry and fusion in vivo and in vitro. Deciphering key steps in virus entry is expected to contribute to rational vaccine and drug design. During this project I aim to establish a world-class laboratory in structural and cellular biology of emerging viruses. The project greatly benefits from our unique biosafety level 3 laboratory offering advanced bio-imaging techniques. Furthermore it will also pave way for similar projects on other infectious viruses. Finally the novel computational image processing methods developed in this project will be broadly applicable for the analysis of flexible biological structures, which often pose the most challenging yet interesting questions in structural biology.
Summary
We aim to understand host cell entry of enveloped viruses at molecular level. A crucial step in this process is when the viral membrane fuses with the cell membrane. Similarly to cell–cell fusion, this step is mediated by fusion proteins (classes I–III). Several medically important viruses, notably dengue and many bunyaviruses, harbour a class II fusion protein. Class II fusion protein structures have been solved in pre- and post-fusion conformation and in some cases different factors promoting fusion have been determined. However, questions about the most important steps of this key process remain unanswered. I will focus on the entry mechanism of bunyaviruses by using cutting-edge, high spatial and temporal resolution bio-imaging techniques. These viruses have been chosen as a model system to maximise the significance of the project: they form an emerging viral threat to humans and animals, no approved vaccines or antivirals exist for human use and they are less studied than other class II fusion protein systems. Cryo-electron microscopy and tomography will be used to solve high-resolution structures (up to ~3 Å) of viruses, in addition to virus–receptor and virus–membrane complexes. Advanced fluorescence microscopy techniques will be used to probe the dynamics of virus entry and fusion in vivo and in vitro. Deciphering key steps in virus entry is expected to contribute to rational vaccine and drug design. During this project I aim to establish a world-class laboratory in structural and cellular biology of emerging viruses. The project greatly benefits from our unique biosafety level 3 laboratory offering advanced bio-imaging techniques. Furthermore it will also pave way for similar projects on other infectious viruses. Finally the novel computational image processing methods developed in this project will be broadly applicable for the analysis of flexible biological structures, which often pose the most challenging yet interesting questions in structural biology.
Max ERC Funding
1 998 375 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym BRAIN2BRAIN
Project Towards two-person neuroscience
Researcher (PI) Riitta Kyllikki Hari
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Call Details Advanced Grant (AdG), LS5, ERC-2008-AdG
Summary Humans interact with other people throughout their lives. This project aims to demonstrate that the complex social shaping of the human brain can be adequately tackled only by taking a leap from the conven-tional single-person neuroscience to two-person neuroscience. We will (1) develop a conceptual framework and experimental setups for two-person neuroscience, (2) apply time-sensitive methods for studies of two interacting persons, monitoring both brain and autonomic nervous activity to also cover the brain body connection, (3) use gaze as an index of subject s attention to simplify signal analysis in natural environments, and (4) apply insights from two-person neuroscience into disorders of social interaction. Brain activity will be recorded with millisecond-accurate whole-scalp (306-channel) magnetoencepha-lography (MEG), associated with EEG, and with the millimeter-accurate 3-tesla functional magnetic reso-nance imaging (fMRI). Heart rate, respiration, galvanic skin response, and pupil diameter inform about body function. A new psychophysiological interaction setting will be built, comprising a two-person eye-tracking system. Novel analysis methods will be developed to follow the interaction and possible synchronization of the two persons signals. This uncoventional approach crosses borders of neuroscience, social psychology, psychophysiology, psychiatry, medical imaging, and signal analysis, with intriguing connections to old philosophical questions, such as intersubjectivity and emphatic attunement. The results could open an unprecedented window into human human, instead of just brain brain, interactions, helping to understand also social disorders, such as autism and schizophrenia. Further applications include master apprentice and patient therapist relationships. Advancing from studies of single persons towards two-person neuroscience shows promise of a break-through in understanding the dynamic social shaping of human brain and mind.
Summary
Humans interact with other people throughout their lives. This project aims to demonstrate that the complex social shaping of the human brain can be adequately tackled only by taking a leap from the conven-tional single-person neuroscience to two-person neuroscience. We will (1) develop a conceptual framework and experimental setups for two-person neuroscience, (2) apply time-sensitive methods for studies of two interacting persons, monitoring both brain and autonomic nervous activity to also cover the brain body connection, (3) use gaze as an index of subject s attention to simplify signal analysis in natural environments, and (4) apply insights from two-person neuroscience into disorders of social interaction. Brain activity will be recorded with millisecond-accurate whole-scalp (306-channel) magnetoencepha-lography (MEG), associated with EEG, and with the millimeter-accurate 3-tesla functional magnetic reso-nance imaging (fMRI). Heart rate, respiration, galvanic skin response, and pupil diameter inform about body function. A new psychophysiological interaction setting will be built, comprising a two-person eye-tracking system. Novel analysis methods will be developed to follow the interaction and possible synchronization of the two persons signals. This uncoventional approach crosses borders of neuroscience, social psychology, psychophysiology, psychiatry, medical imaging, and signal analysis, with intriguing connections to old philosophical questions, such as intersubjectivity and emphatic attunement. The results could open an unprecedented window into human human, instead of just brain brain, interactions, helping to understand also social disorders, such as autism and schizophrenia. Further applications include master apprentice and patient therapist relationships. Advancing from studies of single persons towards two-person neuroscience shows promise of a break-through in understanding the dynamic social shaping of human brain and mind.
Max ERC Funding
2 489 643 €
Duration
Start date: 2009-01-01, End date: 2014-12-31
Project acronym CANCER SIGNALOSOMES
Project Spatially and temporally regulated membrane complexes in cancer cell invasion and cytokinesis
Researcher (PI) Johanna Ivaska
Host Institution (HI) TEKNOLOGIAN TUTKIMUSKESKUS VTT
Call Details Starting Grant (StG), LS1, ERC-2007-StG
Summary Cancer progression, characterized by uncontrolled proliferation and motility of cells, is a complex and deadly process. Integrins, a major cell surface adhesion receptor family, are transmembrane proteins known to regulate cell behaviour by transducing extracellular signals to cytoplasmic protein complexes. We and others have shown that recruitment of specific protein complexes by the cytoplasmic domains of integrins is important in tumorigenesis. Here our aim is to study three interrelated processes in cancer progression which involve integrin signalling, but which have not been elucidated earlier at all. 1) Integrins in cell division (cytokinesis). Since coordinated action of the cytoskeleton and membranes is needed both for cell division and motility, shared integrin functions can regulate both events. 2) Dynamic integrin signalosomes at the leading edge of invading cells. Spatially and temporally regulated, integrin-protein complexes at the front of infiltrating cells are likely to dictate the movement of cancer cells in tissues. 3) Transmembrane segments of integrins as scaffolds for integrin signalling. In addition to cytosolic proteins, integrins most likely interact with proteins within the membrane resulting into new signalling modalities. In this proposal we will use innovative, modern and even unconventional techniques (such as RNAi and live-cell arrays detecting integrin traffic, cell motility and multiplication, laser-microdissection, proteomics and bacterial-two-hybrid screens) to unravel these new integrin functions, for which we have preliminary evidence. Each project will give fundamentally novel mechanistic insight into the role of integrins in cancer. Moreover, these interdisciplinary new openings will increase our understanding in cancer progression in general and will open new possibilities for therapeutic intervention targeting both cancer proliferation and dissemination in the body.
Summary
Cancer progression, characterized by uncontrolled proliferation and motility of cells, is a complex and deadly process. Integrins, a major cell surface adhesion receptor family, are transmembrane proteins known to regulate cell behaviour by transducing extracellular signals to cytoplasmic protein complexes. We and others have shown that recruitment of specific protein complexes by the cytoplasmic domains of integrins is important in tumorigenesis. Here our aim is to study three interrelated processes in cancer progression which involve integrin signalling, but which have not been elucidated earlier at all. 1) Integrins in cell division (cytokinesis). Since coordinated action of the cytoskeleton and membranes is needed both for cell division and motility, shared integrin functions can regulate both events. 2) Dynamic integrin signalosomes at the leading edge of invading cells. Spatially and temporally regulated, integrin-protein complexes at the front of infiltrating cells are likely to dictate the movement of cancer cells in tissues. 3) Transmembrane segments of integrins as scaffolds for integrin signalling. In addition to cytosolic proteins, integrins most likely interact with proteins within the membrane resulting into new signalling modalities. In this proposal we will use innovative, modern and even unconventional techniques (such as RNAi and live-cell arrays detecting integrin traffic, cell motility and multiplication, laser-microdissection, proteomics and bacterial-two-hybrid screens) to unravel these new integrin functions, for which we have preliminary evidence. Each project will give fundamentally novel mechanistic insight into the role of integrins in cancer. Moreover, these interdisciplinary new openings will increase our understanding in cancer progression in general and will open new possibilities for therapeutic intervention targeting both cancer proliferation and dissemination in the body.
Max ERC Funding
1 529 369 €
Duration
Start date: 2008-08-01, End date: 2013-07-31
Project acronym CUMTAS
Project Customized Micro Total Analysis Systems to Study Human Phase I Metabolism
Researcher (PI) Tiina Marjukka Sikanen
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS9, ERC-2012-StG_20111109
Summary The goal of this project is to develop inexpensive, high-throughput technology to screen the thus far unexplored metabolic interactions between environmental and household chemicals and clinically relevant drugs. The main influential focus will be on human phase I metabolism (redox reactions) of common toxicants like agrochemicals and plasticizers. On the basis of their structural resemblance to pharmaceuticals and endogenous compounds, many of these chemicals are suspected to have critical effects on cytochrome P450 metabolism which is the main detoxification route of pharmaceuticals in man. However, with the current analytical instrumentation, screening of such large chemical pool would take several years, and new chemicals would be introduced faster than the old ones are screened. Thus, the main technological goal of this project is to develop novel, practically zero-cost analytical instruments that enable characterization of a compound’s metabolic profile at very high speed (<1 min/sample). This goal is achieved through miniaturization and high degree of integration of analytical instrumentation by microfabrication means, an approach often called lab(oratory)-on-a-chip. The microfabricated arrays are envisioned to incorporate all analytical key functions required (i.e., sample pretreatment, metabolic reaction, separation of the reaction products, detection) on a single chip. Thanks to the reduced dimensions, the amount of chemical waste and consumption of expensive reagents are significantly reduced. In this project, several different microfabrication techniques, from delicate cleanroom processes to extremely simple printing techniques, will be exploited to produce smart microfluidic designs and multifunctional surfaces. Towards the end of the project, more focus will be put on “printable microfluidics” which provides a truly low-cost approach for fabrication of highly customized microfluidic assays. Numerical modelling is also an integral part of the work.
Summary
The goal of this project is to develop inexpensive, high-throughput technology to screen the thus far unexplored metabolic interactions between environmental and household chemicals and clinically relevant drugs. The main influential focus will be on human phase I metabolism (redox reactions) of common toxicants like agrochemicals and plasticizers. On the basis of their structural resemblance to pharmaceuticals and endogenous compounds, many of these chemicals are suspected to have critical effects on cytochrome P450 metabolism which is the main detoxification route of pharmaceuticals in man. However, with the current analytical instrumentation, screening of such large chemical pool would take several years, and new chemicals would be introduced faster than the old ones are screened. Thus, the main technological goal of this project is to develop novel, practically zero-cost analytical instruments that enable characterization of a compound’s metabolic profile at very high speed (<1 min/sample). This goal is achieved through miniaturization and high degree of integration of analytical instrumentation by microfabrication means, an approach often called lab(oratory)-on-a-chip. The microfabricated arrays are envisioned to incorporate all analytical key functions required (i.e., sample pretreatment, metabolic reaction, separation of the reaction products, detection) on a single chip. Thanks to the reduced dimensions, the amount of chemical waste and consumption of expensive reagents are significantly reduced. In this project, several different microfabrication techniques, from delicate cleanroom processes to extremely simple printing techniques, will be exploited to produce smart microfluidic designs and multifunctional surfaces. Towards the end of the project, more focus will be put on “printable microfluidics” which provides a truly low-cost approach for fabrication of highly customized microfluidic assays. Numerical modelling is also an integral part of the work.
Max ERC Funding
1 499 668 €
Duration
Start date: 2013-05-01, End date: 2019-02-28
Project acronym DIADRUG
Project Insulin resistance and diabetic nephropathy - development of novel in vivo models for drug discovery
Researcher (PI) Sanna Lehtonen
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS9, ERC-2009-StG
Summary Up to one third of diabetic patients develop nephropathy, a serious complication of diabetes. Microalbuminuria is the earliest sign of the complication, which may ultimately develop to end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance and metabolic syndrome are associated with an increased risk for diabetic nephropathy. Interestingly, glomerular epithelial cells or podocytes have recently been shown to be insulin responsive. Further, nephrin, a key structural component of podocytes, is essential for insulin action in these cells. Our novel findings show that adaptor protein CD2AP, an interaction partner of nephrin, associates with regulators of insulin signaling and glucose transport in glomeruli. The results suggest that nephrin and CD2AP are involved, by association with these proteins, in the regulation of insulin signaling and glucose transport in podocytes. We hypothesize that podocytes can develop insulin resistance and that disturbances in insulin response affect podocyte function and contribute to the development of diabetic nephropathy. The aim of this project is to clarify the mechanisms leading to development of insulin resistance in podocytes and to study the association between insulin resistance and the development of diabetic nephropathy. For this we will develop transgenic zebrafish and mouse models by overexpressing/knocking down insulin signaling-associated proteins specifically in podocytes. Further, we aim to identify novel drug leads to treat insulin resistance and diabetic nephropathy by performing high-throughput small molecule library screens on the developed transgenic fish models. The ultimate goal is to find a treatment to combat the early stages of diabetic nephropathy in humans.
Summary
Up to one third of diabetic patients develop nephropathy, a serious complication of diabetes. Microalbuminuria is the earliest sign of the complication, which may ultimately develop to end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance and metabolic syndrome are associated with an increased risk for diabetic nephropathy. Interestingly, glomerular epithelial cells or podocytes have recently been shown to be insulin responsive. Further, nephrin, a key structural component of podocytes, is essential for insulin action in these cells. Our novel findings show that adaptor protein CD2AP, an interaction partner of nephrin, associates with regulators of insulin signaling and glucose transport in glomeruli. The results suggest that nephrin and CD2AP are involved, by association with these proteins, in the regulation of insulin signaling and glucose transport in podocytes. We hypothesize that podocytes can develop insulin resistance and that disturbances in insulin response affect podocyte function and contribute to the development of diabetic nephropathy. The aim of this project is to clarify the mechanisms leading to development of insulin resistance in podocytes and to study the association between insulin resistance and the development of diabetic nephropathy. For this we will develop transgenic zebrafish and mouse models by overexpressing/knocking down insulin signaling-associated proteins specifically in podocytes. Further, we aim to identify novel drug leads to treat insulin resistance and diabetic nephropathy by performing high-throughput small molecule library screens on the developed transgenic fish models. The ultimate goal is to find a treatment to combat the early stages of diabetic nephropathy in humans.
Max ERC Funding
2 000 000 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym ForceMorph
Project The integration of cell signalling and mechanical forces in vascular morphology
Researcher (PI) Cecilia Maria SAHLGREN
Host Institution (HI) ABO AKADEMI
Call Details Consolidator Grant (CoG), LS9, ERC-2017-COG
Summary Cardiovascular diseases represent the principal worldwide medical challenge of the 21st century (WHO), and new concepts to treat, predict and even prevent these diseases are needed. Structural remodelling of the vasculature in response to changes in blood flow is important to maintain mechanical homeostasis, and many diseases are related to defects in tissue morphology and mechanical imbalance. Signalling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via the Notch pathway regulates the morphology and structural remodelling of the arterial wall. Importantly, Notch offers handles for therapeutic control and thus opportunities for treatment of malformation and adaptation. However, we lack the essential understanding of how hemodynamic forces integrate with Notch signalling to rationally and responsibly target Notch in vascular therapies. The complexity of the problem requires new tools and an interdisciplinary approach. Our project integrates engineering, computational modelling, with cell biology and in vivo model systems to address the question. In vivo models will validate the in in vitro model systems to ensure that they are reproducible and reflect the reality. Through this integrated approach we will enable new therapeutic developments.
The specific objectives of the project are to:
1) Study EC-VSMC signalling real time, at high resolution by a novel biomimetic 4D Artery-on-Chip that recapitulates the cell-composition, -organisation and hemodynamic forces of the physiological artery
2) Develop a computational model of the arterial wall that include the mechanosensitivity of Notch signalling to predict how the complex interactions affect arterial morphology and remodelling
3) Use in vivo animal models to elucidate how regulation of Notch signalling affects tissue morphology and remodelling in response to changes in hemodynamic conditions
Summary
Cardiovascular diseases represent the principal worldwide medical challenge of the 21st century (WHO), and new concepts to treat, predict and even prevent these diseases are needed. Structural remodelling of the vasculature in response to changes in blood flow is important to maintain mechanical homeostasis, and many diseases are related to defects in tissue morphology and mechanical imbalance. Signalling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via the Notch pathway regulates the morphology and structural remodelling of the arterial wall. Importantly, Notch offers handles for therapeutic control and thus opportunities for treatment of malformation and adaptation. However, we lack the essential understanding of how hemodynamic forces integrate with Notch signalling to rationally and responsibly target Notch in vascular therapies. The complexity of the problem requires new tools and an interdisciplinary approach. Our project integrates engineering, computational modelling, with cell biology and in vivo model systems to address the question. In vivo models will validate the in in vitro model systems to ensure that they are reproducible and reflect the reality. Through this integrated approach we will enable new therapeutic developments.
The specific objectives of the project are to:
1) Study EC-VSMC signalling real time, at high resolution by a novel biomimetic 4D Artery-on-Chip that recapitulates the cell-composition, -organisation and hemodynamic forces of the physiological artery
2) Develop a computational model of the arterial wall that include the mechanosensitivity of Notch signalling to predict how the complex interactions affect arterial morphology and remodelling
3) Use in vivo animal models to elucidate how regulation of Notch signalling affects tissue morphology and remodelling in response to changes in hemodynamic conditions
Max ERC Funding
1 919 599 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym FREEDLES
Project From needles to landscapes: a novel approach to scaling forest spectra
Researcher (PI) Miina Alina RAUTIAINEN
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Call Details Consolidator Grant (CoG), LS9, ERC-2017-COG
Summary Accounting for vegetation structure – clumping of foliage into shoots or crowns – is the largest remaining challenge in modelling scattered and absorbed radiation in complex vegetation canopies such as forests. Clumping controls the radiation regime of forest canopies, yet it is poorly quantified. Currently, the communities working with vegetation structure and optical measurements do not have a common understanding of the concept. The FREEDLES project sets out to develop a universal method for quantifying clumping of foliage in forests based on detailed 3D structure and spectral reflectance data. Clumping will be linked to photon recollision probability, an exciting new development in the field of photon transport modelling. Photon recollision probability will, in turn, be used to develop a spectral scaling algorithm which will connect the spectra of vegetation at all hierarchical levels from needles and leaves to crowns, stands and landscapes. The spectral scaling algorithm will be validated with detailed reference measurements in both laboratory and natural conditions, and applied to interpret forest variables from satellite images at different spatial resolutions. The proposed approach is contrary to many other lines of current development where more complexity is favoured in canopy radiation models. If successful, the approach will significantly improve estimates of absorbed and scattered radiation fields in forests and retrieval results of forest biophysical variables from satellite data. Future applications can also be expected in global radiation and carbon balance estimation and in chlorophyll fluorescence models for forests. Most importantly, the spectral scaling model will open new horizons for our scientific understanding of photon-vegetation interactions.
Summary
Accounting for vegetation structure – clumping of foliage into shoots or crowns – is the largest remaining challenge in modelling scattered and absorbed radiation in complex vegetation canopies such as forests. Clumping controls the radiation regime of forest canopies, yet it is poorly quantified. Currently, the communities working with vegetation structure and optical measurements do not have a common understanding of the concept. The FREEDLES project sets out to develop a universal method for quantifying clumping of foliage in forests based on detailed 3D structure and spectral reflectance data. Clumping will be linked to photon recollision probability, an exciting new development in the field of photon transport modelling. Photon recollision probability will, in turn, be used to develop a spectral scaling algorithm which will connect the spectra of vegetation at all hierarchical levels from needles and leaves to crowns, stands and landscapes. The spectral scaling algorithm will be validated with detailed reference measurements in both laboratory and natural conditions, and applied to interpret forest variables from satellite images at different spatial resolutions. The proposed approach is contrary to many other lines of current development where more complexity is favoured in canopy radiation models. If successful, the approach will significantly improve estimates of absorbed and scattered radiation fields in forests and retrieval results of forest biophysical variables from satellite data. Future applications can also be expected in global radiation and carbon balance estimation and in chlorophyll fluorescence models for forests. Most importantly, the spectral scaling model will open new horizons for our scientific understanding of photon-vegetation interactions.
Max ERC Funding
1 963 590 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym IPLASTICITY
Project Induction of juvenile-like plasticity in the adult brain
Researcher (PI) Eero Castrén
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Advanced Grant (AdG), LS5, ERC-2012-ADG_20120314
Summary Neuronal networks are tuned to optimally represent external and internal milieu through neuronal plasticity during critical periods of juvenile life. After the closure of the critical periods, plasticity is considered to be much more limited. In a series of landmark studies, we have shown that critical period-like plasticity can be reactivated in the adult mammalian brain by pharmacological treatment with the antidepressant fluoxetine. These ground-breaking studies establish a new principle, induced juvenile-like plasticity (iPlasticity) and define a new class of drugs, iPlastic drugs. For optimal results, iPlastic drug must be combined with physical or psychological rehabilitation, which guide the plastic networks and together allow better adaptation towards changing environment. iPlasticity may facilitate functional recovery after brain injury and underlie the enhanced efficacy of combined antidepressant treatment and psychotherapy.
We have uncovered iPlasticity as an exciting new concept and established experimental models to study the molecular, cellular and network level mechanisms underlying it. We will here focus on the role of neurotrophin BDNF, because our previous and unpublished work clearly shows that BDNF and its receptors TrkB and p75 are essential and sufficient for iPlasticity. We have found that a major developmental reorganization in TrkB signalling takes place coinciding with the end of critical periods, and its reversal may underlie iPlasticity. We will utilize our resources as a leading lab in BDNF effects in adult brain and through novel controlled transgenic models, genomics and proteomics, we will reveal the role of BDNF signalling through TrkB and p75 in brain maturation, iPlasticity and brain disorders. Understanding the neurobiological background of iPlasticity will be vital for iPlastic drug development and the numerous translational applications of iPlasticity clearly in sight.
Summary
Neuronal networks are tuned to optimally represent external and internal milieu through neuronal plasticity during critical periods of juvenile life. After the closure of the critical periods, plasticity is considered to be much more limited. In a series of landmark studies, we have shown that critical period-like plasticity can be reactivated in the adult mammalian brain by pharmacological treatment with the antidepressant fluoxetine. These ground-breaking studies establish a new principle, induced juvenile-like plasticity (iPlasticity) and define a new class of drugs, iPlastic drugs. For optimal results, iPlastic drug must be combined with physical or psychological rehabilitation, which guide the plastic networks and together allow better adaptation towards changing environment. iPlasticity may facilitate functional recovery after brain injury and underlie the enhanced efficacy of combined antidepressant treatment and psychotherapy.
We have uncovered iPlasticity as an exciting new concept and established experimental models to study the molecular, cellular and network level mechanisms underlying it. We will here focus on the role of neurotrophin BDNF, because our previous and unpublished work clearly shows that BDNF and its receptors TrkB and p75 are essential and sufficient for iPlasticity. We have found that a major developmental reorganization in TrkB signalling takes place coinciding with the end of critical periods, and its reversal may underlie iPlasticity. We will utilize our resources as a leading lab in BDNF effects in adult brain and through novel controlled transgenic models, genomics and proteomics, we will reveal the role of BDNF signalling through TrkB and p75 in brain maturation, iPlasticity and brain disorders. Understanding the neurobiological background of iPlasticity will be vital for iPlastic drug development and the numerous translational applications of iPlasticity clearly in sight.
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym Micro-RIP
Project Functional analysis of uncultivated microbes using radioisotope probing
Researcher (PI) Marja Tiirola
Host Institution (HI) JYVASKYLAN YLIOPISTO
Call Details Consolidator Grant (CoG), LS9, ERC-2013-CoG
Summary Environmental microbiology calls for more advanced research methods for resolving microbial functions and regulation in environmental samples. The proposed project introduces an unconventional technology, radioisotope probing (RIP). This approach is based on the invention of radioactivity measurement via pH analysis. When the analysis of radioactivity is now combined with semiconductor sequencing, the technology offers two-dimensional analysis of millions of molecules on a sequencing chip. Hybridization of experimentally labeled RNA and radioactivity measurement would provide a second dimension for the sequencing analysis, facilitating various new applications in environmental microbiology, as well as potential applications for different needs of biochemistry and medical research.
The project aims to develop and test three novel RIP applications to analyse functional diversity, transcriptional regulation and mRNA processing in microbial communities, especially focusing on prokaryotic species. The applications are utilized for studying regulation of microbial decomposition, which is the key question, when predicting the effects of climate change. It is hypothesized that more frequent flood, droughts and redox fluctuations can prime the biodegradation of otherwise stable boreal carbon pools.
Functional diversity of microbes utilizing model and complex substrates is studied in terrestrial and aquatic environments using time-series samplings and labeling experiments. Prevailing mechanisms in the cellular regulation in microbial communities are investigated using community-level methylation and regulatory RNA patterns. The effect of external stressor (toxicants and changing oxygen regimes) on these patterns is analyzed using sequencing and RIP to reveal the mechanisms regulating the processes beyond mere community composition.
Summary
Environmental microbiology calls for more advanced research methods for resolving microbial functions and regulation in environmental samples. The proposed project introduces an unconventional technology, radioisotope probing (RIP). This approach is based on the invention of radioactivity measurement via pH analysis. When the analysis of radioactivity is now combined with semiconductor sequencing, the technology offers two-dimensional analysis of millions of molecules on a sequencing chip. Hybridization of experimentally labeled RNA and radioactivity measurement would provide a second dimension for the sequencing analysis, facilitating various new applications in environmental microbiology, as well as potential applications for different needs of biochemistry and medical research.
The project aims to develop and test three novel RIP applications to analyse functional diversity, transcriptional regulation and mRNA processing in microbial communities, especially focusing on prokaryotic species. The applications are utilized for studying regulation of microbial decomposition, which is the key question, when predicting the effects of climate change. It is hypothesized that more frequent flood, droughts and redox fluctuations can prime the biodegradation of otherwise stable boreal carbon pools.
Functional diversity of microbes utilizing model and complex substrates is studied in terrestrial and aquatic environments using time-series samplings and labeling experiments. Prevailing mechanisms in the cellular regulation in microbial communities are investigated using community-level methylation and regulatory RNA patterns. The effect of external stressor (toxicants and changing oxygen regimes) on these patterns is analyzed using sequencing and RIP to reveal the mechanisms regulating the processes beyond mere community composition.
Max ERC Funding
1 997 913 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
