Project acronym ActiveBioFluids
Project Origins of Collective Motion in Active Biofluids
Researcher (PI) Daniel TAM
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Country Netherlands
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary The emergence of coherent behaviour is ubiquitous in the natural world and has long captivated biologists and physicists alike. One area of growing interest is the collective motion and synchronization arising within and between simple motile organisms. My goal is to develop and use a novel experimental approach to unravel the origins of spontaneous coherent motion in three model systems of biofluids: (1) the synchronization of the two flagella of green algae Chlamydomonas Rheinhardtii, (2) the metachronal wave in the cilia of protist Paramecium and (3) the collective motion of swimming microorganisms in active suspensions. Understanding the mechanisms leading to collective motion is of tremendous importance because it is crucial to many biological processes such as mechanical signal transduction, embryonic development and biofilm formation.
Up till now, most of the work has been theoretical and has led to the dominant view that hydrodynamic interactions are the main driving force for synchronization and collective motion. Recent experiments have challenged this view and highlighted the importance of direct mechanical contact. New experimental studies are now crucially needed. The state-of-the-art of experimental approaches consists of observations of unperturbed cells. The key innovation in our approach is to dynamically interact with microorganisms in real-time, at the relevant time and length scales. I will investigate the origins of coherent motion by reproducing synthetically the mechanical signatures of physiological flows and direct mechanical interactions and track precisely the response of the organism to the perturbations. Our new approach will incorporate optical tweezers to interact with motile cells, and a unique μ-Tomographic PIV setup to track their 3D micron-scale motion.
This proposal tackles a timely question in biophysics and will yield new insight into the fundamental principles underlying collective motion in active biological matter.
Summary
The emergence of coherent behaviour is ubiquitous in the natural world and has long captivated biologists and physicists alike. One area of growing interest is the collective motion and synchronization arising within and between simple motile organisms. My goal is to develop and use a novel experimental approach to unravel the origins of spontaneous coherent motion in three model systems of biofluids: (1) the synchronization of the two flagella of green algae Chlamydomonas Rheinhardtii, (2) the metachronal wave in the cilia of protist Paramecium and (3) the collective motion of swimming microorganisms in active suspensions. Understanding the mechanisms leading to collective motion is of tremendous importance because it is crucial to many biological processes such as mechanical signal transduction, embryonic development and biofilm formation.
Up till now, most of the work has been theoretical and has led to the dominant view that hydrodynamic interactions are the main driving force for synchronization and collective motion. Recent experiments have challenged this view and highlighted the importance of direct mechanical contact. New experimental studies are now crucially needed. The state-of-the-art of experimental approaches consists of observations of unperturbed cells. The key innovation in our approach is to dynamically interact with microorganisms in real-time, at the relevant time and length scales. I will investigate the origins of coherent motion by reproducing synthetically the mechanical signatures of physiological flows and direct mechanical interactions and track precisely the response of the organism to the perturbations. Our new approach will incorporate optical tweezers to interact with motile cells, and a unique μ-Tomographic PIV setup to track their 3D micron-scale motion.
This proposal tackles a timely question in biophysics and will yield new insight into the fundamental principles underlying collective motion in active biological matter.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym APROCS
Project Automated Linear Parameter-Varying Modeling and Control Synthesis for Nonlinear Complex Systems
Researcher (PI) Roland TOTH
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Country Netherlands
Call Details Starting Grant (StG), PE7, ERC-2016-STG
Summary Linear Parameter-Varying (LPV) systems are flexible mathematical models capable of representing Nonlinear (NL)/Time-Varying (TV) dynamical behaviors of complex physical systems (e.g., wafer scanners, car engines, chemical reactors), often encountered in engineering, via a linear structure. The LPV framework provides computationally efficient and robust approaches to synthesize digital controllers that can ensure desired operation of such systems - making it attractive to (i) high-tech mechatronic, (ii) automotive and (iii) chemical-process applications. Such a framework is important to meet with the increasing operational demands of systems in these industrial sectors and to realize future technological targets. However, recent studies have shown that, to fully exploit the potential of the LPV framework, a number of limiting factors of the underlying theory ask a for serious innovation, as currently it is not understood how to (1) automate exact and low-complexity LPV modeling of real-world applications and how to refine uncertain aspects of these models efficiently by the help of measured data, (2) incorporate control objectives directly into modeling and to develop model reduction approaches for control, and (3) how to see modeling & control synthesis as a unified, closed-loop system synthesis approach directly oriented for the underlying NL/TV system. Furthermore, due to the increasingly cyber-physical nature of applications, (4) control synthesis is needed in a plug & play fashion, where if sub-systems are modified or exchanged, then the control design and the model of the whole system are only incrementally updated. This project aims to surmount Challenges (1)-(4) by establishing an innovative revolution of the LPV framework supported by a software suite and extensive empirical studies on real-world industrial applications; with a potential to ensure a leading role of technological innovation of the EU in the high-impact industrial sectors (i)-(iii).
Summary
Linear Parameter-Varying (LPV) systems are flexible mathematical models capable of representing Nonlinear (NL)/Time-Varying (TV) dynamical behaviors of complex physical systems (e.g., wafer scanners, car engines, chemical reactors), often encountered in engineering, via a linear structure. The LPV framework provides computationally efficient and robust approaches to synthesize digital controllers that can ensure desired operation of such systems - making it attractive to (i) high-tech mechatronic, (ii) automotive and (iii) chemical-process applications. Such a framework is important to meet with the increasing operational demands of systems in these industrial sectors and to realize future technological targets. However, recent studies have shown that, to fully exploit the potential of the LPV framework, a number of limiting factors of the underlying theory ask a for serious innovation, as currently it is not understood how to (1) automate exact and low-complexity LPV modeling of real-world applications and how to refine uncertain aspects of these models efficiently by the help of measured data, (2) incorporate control objectives directly into modeling and to develop model reduction approaches for control, and (3) how to see modeling & control synthesis as a unified, closed-loop system synthesis approach directly oriented for the underlying NL/TV system. Furthermore, due to the increasingly cyber-physical nature of applications, (4) control synthesis is needed in a plug & play fashion, where if sub-systems are modified or exchanged, then the control design and the model of the whole system are only incrementally updated. This project aims to surmount Challenges (1)-(4) by establishing an innovative revolution of the LPV framework supported by a software suite and extensive empirical studies on real-world industrial applications; with a potential to ensure a leading role of technological innovation of the EU in the high-impact industrial sectors (i)-(iii).
Max ERC Funding
1 493 561 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym BinCosmos
Project The Impact of Massive Binaries Through Cosmic Time
Researcher (PI) Selma DE MINK
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Starting Grant (StG), PE9, ERC-2016-STG
Summary Massive stars play many key roles in Astrophysics. As COSMIC ENGINES they transformed the pristine Universe left after the Big Bang into our modern Universe. We use massive stars, their explosions and products as COSMIC PROBES to study the conditions in the distant Universe and the extreme physics inaccessible at earth. Models of massive stars are thus widely applied. A central common assumption is that massive stars are non-rotating single objects, in stark contrast with new data. Recent studies show that majority (70% according to our data) will experience severe interaction with a companion (Sana, de Mink et al. Science 2012).
I propose to conduct the most ambitious and extensive exploration to date of the effects of binarity and rotation on the lives and fates of massive stars to (I) transform our understanding of the complex physical processes and how they operate in the vast parameter space and (II) explore the cosmological implications after calibrating and verifying the models. To achieve this ambitious objective I will use an innovative computational approach that combines the strength of two highly complementary codes and seek direct confrontation with observations to overcome the computational challenges that inhibited previous work.
This timely project will provide the urgent theory framework needed for interpretation and guiding of observing programs with the new facilities (JWST, LSST, aLIGO/VIRGO). Public release of the model grids and code will ensure wide impact of this project. I am in the unique position to successfully lead this project because of my (i) extensive experience modeling the complex physical processes, (ii) leading role in introducing large statistical simulations in the massive star community and (iii) direct involvement in surveys that will be used in this project.
Summary
Massive stars play many key roles in Astrophysics. As COSMIC ENGINES they transformed the pristine Universe left after the Big Bang into our modern Universe. We use massive stars, their explosions and products as COSMIC PROBES to study the conditions in the distant Universe and the extreme physics inaccessible at earth. Models of massive stars are thus widely applied. A central common assumption is that massive stars are non-rotating single objects, in stark contrast with new data. Recent studies show that majority (70% according to our data) will experience severe interaction with a companion (Sana, de Mink et al. Science 2012).
I propose to conduct the most ambitious and extensive exploration to date of the effects of binarity and rotation on the lives and fates of massive stars to (I) transform our understanding of the complex physical processes and how they operate in the vast parameter space and (II) explore the cosmological implications after calibrating and verifying the models. To achieve this ambitious objective I will use an innovative computational approach that combines the strength of two highly complementary codes and seek direct confrontation with observations to overcome the computational challenges that inhibited previous work.
This timely project will provide the urgent theory framework needed for interpretation and guiding of observing programs with the new facilities (JWST, LSST, aLIGO/VIRGO). Public release of the model grids and code will ensure wide impact of this project. I am in the unique position to successfully lead this project because of my (i) extensive experience modeling the complex physical processes, (ii) leading role in introducing large statistical simulations in the massive star community and (iii) direct involvement in surveys that will be used in this project.
Max ERC Funding
1 926 634 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym CALCEAM
Project Cooperative Acceptor Ligands for Catalysis with Earth-Abundant Metals
Researcher (PI) Marc-Etienne Moret
Host Institution (HI) UNIVERSITEIT UTRECHT
Country Netherlands
Call Details Starting Grant (StG), PE5, ERC-2016-STG
Summary Homogeneous catalysis is of prime importance for the selective synthesis of high added value chemicals. Many of the currently available catalysts rely on noble metals (Ru, Os, Rh, Ir, Pd, Pt), which suffer from a high toxicity and environmental impact in addition to their high cost, calling for the development of new systems based on first-row transition metals (Mn, Fe, Co, Ni, Cu). The historical paradigm for catalyst design, i.e. one or more donor ligands giving electron density to stabilize a metal center and tune its reactivity, is currently being challenged by the development of acceptor ligands that mostly withdraw electron density from the metal center upon binding. In the last decade, such ligands – mostly based on boron and heavier main-group elements – have evolved from a structural curiosity to a powerful tool in designing new reactive units for homogeneous catalysis.
I will develop a novel class of ligands that use C=E (E=O, S, NR) multiple bonds anchored in close proximity to the metal by phosphine tethers. The electrophilic C=E multiple bond is designed to act as an acceptor moiety that adapts its binding mode to the electronic structure of reactive intermediates with the unique additional possibility of involving the lone pairs on heteroelement E in cooperative reactivity. Building on preliminary results showing that a C=O bond can function as a hemilabile ligand in a catalytic cycle, I will undertake a systematic, experimental and theoretical investigation of the structure and reactivity of M–C–E three membered rings formed by side-on coordination of C=E bonds to a first-row metal. Their ability to facilitate multi-electron transformations (oxidative addition, atom/group transfer reactions) will be investigated. In particular, hemilability of the C=E bond is expected to facilitate challenging C–C bond forming reactions mediated by Fe and Ni. This approach will demonstrate a new conceptual tool for the design of efficient base-metal catalysts.
Summary
Homogeneous catalysis is of prime importance for the selective synthesis of high added value chemicals. Many of the currently available catalysts rely on noble metals (Ru, Os, Rh, Ir, Pd, Pt), which suffer from a high toxicity and environmental impact in addition to their high cost, calling for the development of new systems based on first-row transition metals (Mn, Fe, Co, Ni, Cu). The historical paradigm for catalyst design, i.e. one or more donor ligands giving electron density to stabilize a metal center and tune its reactivity, is currently being challenged by the development of acceptor ligands that mostly withdraw electron density from the metal center upon binding. In the last decade, such ligands – mostly based on boron and heavier main-group elements – have evolved from a structural curiosity to a powerful tool in designing new reactive units for homogeneous catalysis.
I will develop a novel class of ligands that use C=E (E=O, S, NR) multiple bonds anchored in close proximity to the metal by phosphine tethers. The electrophilic C=E multiple bond is designed to act as an acceptor moiety that adapts its binding mode to the electronic structure of reactive intermediates with the unique additional possibility of involving the lone pairs on heteroelement E in cooperative reactivity. Building on preliminary results showing that a C=O bond can function as a hemilabile ligand in a catalytic cycle, I will undertake a systematic, experimental and theoretical investigation of the structure and reactivity of M–C–E three membered rings formed by side-on coordination of C=E bonds to a first-row metal. Their ability to facilitate multi-electron transformations (oxidative addition, atom/group transfer reactions) will be investigated. In particular, hemilability of the C=E bond is expected to facilitate challenging C–C bond forming reactions mediated by Fe and Ni. This approach will demonstrate a new conceptual tool for the design of efficient base-metal catalysts.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-08-01, End date: 2022-07-31
Project acronym DELPHI
Project DELPHI: a framework to study Dark Matter and the emergence of galaxies in the epoch of reionization
Researcher (PI) Pratika DAYAL
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Country Netherlands
Call Details Starting Grant (StG), PE9, ERC-2016-STG
Summary Our Universe started as a dark featureless sea of hydrogen, helium, and dark matter of unknown composition about 13 and a half billion years ago. The earliest galaxies lit up the Universe with pinpricks of light, ushering in the era of ‘cosmic dawn’. These galaxies represent the primary building blocks of all subsequent galaxies and the sources of the first (hydrogen ionizing) photons that could break apart the hydrogen atoms suffusing all of space starting the process of ‘cosmic reionization’. By virtue of being the smallest bound structures in the early Universe, these galaxies also provide an excellent testbed for models wherein Dark Matter is composed of warm, fast moving particles as opposed to the sluggish heavy particles used in the standard Cold Dark Matter paradigm.
Exploiting the power of the latest cosmological simulations as well as semi-analytic modelling rooted in first principles, DELPHI will build a coherent and predictive model to answer three of the key outstanding questions in physical cosmology:
- how did the interlinked processes of galaxy formation and reionization drive each other?
- what were the physical properties of early galaxies and how have they evolved through time to give rise to the galaxy properties we see today?
- what is the nature (mass) of the mysterious Dark Matter that makes up 80% of the matter content in the Universe?
The timescale of the ERC represents an excellent opportunity for progress on these fundamental questions: observations with cutting-edge instruments (e.g. the Hubble and Subaru telescopes) are providing the first tantalising glimpses of early galaxies assembling in an infant Universe, required to pin down theoretical models. The realistic results obtained by DELPHI will also be vital in determining survey strategies and exploiting synergies between forthcoming key state-of-the-art instruments such as the European-Extremely Large Telescope, the James Webb Space Telescope and the Square Kilometre Array.
Summary
Our Universe started as a dark featureless sea of hydrogen, helium, and dark matter of unknown composition about 13 and a half billion years ago. The earliest galaxies lit up the Universe with pinpricks of light, ushering in the era of ‘cosmic dawn’. These galaxies represent the primary building blocks of all subsequent galaxies and the sources of the first (hydrogen ionizing) photons that could break apart the hydrogen atoms suffusing all of space starting the process of ‘cosmic reionization’. By virtue of being the smallest bound structures in the early Universe, these galaxies also provide an excellent testbed for models wherein Dark Matter is composed of warm, fast moving particles as opposed to the sluggish heavy particles used in the standard Cold Dark Matter paradigm.
Exploiting the power of the latest cosmological simulations as well as semi-analytic modelling rooted in first principles, DELPHI will build a coherent and predictive model to answer three of the key outstanding questions in physical cosmology:
- how did the interlinked processes of galaxy formation and reionization drive each other?
- what were the physical properties of early galaxies and how have they evolved through time to give rise to the galaxy properties we see today?
- what is the nature (mass) of the mysterious Dark Matter that makes up 80% of the matter content in the Universe?
The timescale of the ERC represents an excellent opportunity for progress on these fundamental questions: observations with cutting-edge instruments (e.g. the Hubble and Subaru telescopes) are providing the first tantalising glimpses of early galaxies assembling in an infant Universe, required to pin down theoretical models. The realistic results obtained by DELPHI will also be vital in determining survey strategies and exploiting synergies between forthcoming key state-of-the-art instruments such as the European-Extremely Large Telescope, the James Webb Space Telescope and the Square Kilometre Array.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym DRAGNET
Project "DRAGNET: A high-speed, wide-angle camera for catching extreme astrophysical events"
Researcher (PI) Jason William Thomas Hessels
Host Institution (HI) STICHTING ASTRON, NETHERLANDS INSTITUTE FOR RADIO ASTRONOMY
Country Netherlands
Call Details Starting Grant (StG), PE9, ERC-2013-StG
Summary "Looking up on a starry night, it’s easy to imagine that the Universe is unchanging. In reality, however, the Universe is teeming with activity: there are massive explosions from accreting black holes, bright radio flashes from ultra-magnetic pulsars, and likely other spectacles that have so far escaped our prying eyes. These fleeting events can happen faster than the blink of an eye and, importantly, they trace the most extreme astrophysical phenomena. Catching these rare performances poses a major challenge for observational astronomers, but the scientific payoff is well worth the effort.
With this proposal, I will mould the Low-Frequency Array (LOFAR) telescope into DRAGNET, the world's premier high-speed, wide-angle camera for radio astronomy. Radio waves are a unique and powerful way of investigating the most extreme astrophysical processes. With DRAGNET I will characterize the rate of fast radio transients, i.e. astrophysical bursts lasting less than a second, and search for new astrophysical phenomena in this largely unexplored domain. This has the potential to give us transformative insight into the extremes of gravity and dense matter. Alongside this, I will simultaneously monitor hundreds of radio-emitting neutron stars (pulsars) on a regular basis. This will allow me to understand why some neutron stars pulse regularly, while others show rapid switches in their emission properties. This will address the physics behind the strongest magnetic fields in the Universe.
I have led the construction of LOFAR's high-time-resolution observing capabilities; in this project I will capitalize on that investment and do cutting-edge science that is beyond the reach of any other existing telescope. Simply put, this project will establish a world-leading research group in the emerging field of fast radio transients and will crystallize the wide-field radio telescope as an essential tool for unveiling the bustling activity that makes our Universe so interesting to study."
Summary
"Looking up on a starry night, it’s easy to imagine that the Universe is unchanging. In reality, however, the Universe is teeming with activity: there are massive explosions from accreting black holes, bright radio flashes from ultra-magnetic pulsars, and likely other spectacles that have so far escaped our prying eyes. These fleeting events can happen faster than the blink of an eye and, importantly, they trace the most extreme astrophysical phenomena. Catching these rare performances poses a major challenge for observational astronomers, but the scientific payoff is well worth the effort.
With this proposal, I will mould the Low-Frequency Array (LOFAR) telescope into DRAGNET, the world's premier high-speed, wide-angle camera for radio astronomy. Radio waves are a unique and powerful way of investigating the most extreme astrophysical processes. With DRAGNET I will characterize the rate of fast radio transients, i.e. astrophysical bursts lasting less than a second, and search for new astrophysical phenomena in this largely unexplored domain. This has the potential to give us transformative insight into the extremes of gravity and dense matter. Alongside this, I will simultaneously monitor hundreds of radio-emitting neutron stars (pulsars) on a regular basis. This will allow me to understand why some neutron stars pulse regularly, while others show rapid switches in their emission properties. This will address the physics behind the strongest magnetic fields in the Universe.
I have led the construction of LOFAR's high-time-resolution observing capabilities; in this project I will capitalize on that investment and do cutting-edge science that is beyond the reach of any other existing telescope. Simply put, this project will establish a world-leading research group in the emerging field of fast radio transients and will crystallize the wide-field radio telescope as an essential tool for unveiling the bustling activity that makes our Universe so interesting to study."
Max ERC Funding
1 964 587 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym GASPARCON
Project Molecular steps of gas-to-particle conversion: From oxidation to precursors, clusters and secondary aerosol particles.
Researcher (PI) Mikko SIPILae
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Starting Grant (StG), PE10, ERC-2016-STG
Summary Atmospheric aerosol particles impact Earth’s climate, by directly scattering sunlight and indirectly by affecting cloud properties. The largest uncertainties in climate change projections are associated with the atmospheric aerosol system that has been altered by anthropogenic activities. A major source of that uncertainty involves the formation of secondary particles and cloud condensation nuclei from natural and anthropogenic emissions of volatile compounds. This research challenge persists despite significant efforts within recent decades.
I will build a research group that aims to resolve the atmospheric oxidation processes that convert volatile trace gases to particle precursor vapours, clusters and new aerosol particles. We will create novel measurement techniques and utilize the tremendous potential of mass spectrometry for detection of i) particle precursor vapours ii) oxidants, both conventional but also recently discovered stabilized Criegee intermediates, and, most importantly, iii) newly formed clusters. These methods and instrumentation will be applied for resolving the initial steps of new particle formation on molecular level from oxidation to clusters and stable aerosol particles. To reach these goals, targeted laboratory and field experiments together with long term field measurements will be performed employing the state-of-the-art instrumentation developed.
Principal outcomes of this project include i) new experimental methods and techniques vital for atmospheric research and a deep understanding of ii) oxidation pathways producing aerosol particle precursors, iii) the initial molecular steps of new particle formation and iv) mechanisms of growth of freshly formed clusters toward larger sizes, particularly in the crucial size range of a few nanometers. The conceptual understanding obtained during this project will open multiple new research horizons from oxidation chemistry to Earth system modeling.
Summary
Atmospheric aerosol particles impact Earth’s climate, by directly scattering sunlight and indirectly by affecting cloud properties. The largest uncertainties in climate change projections are associated with the atmospheric aerosol system that has been altered by anthropogenic activities. A major source of that uncertainty involves the formation of secondary particles and cloud condensation nuclei from natural and anthropogenic emissions of volatile compounds. This research challenge persists despite significant efforts within recent decades.
I will build a research group that aims to resolve the atmospheric oxidation processes that convert volatile trace gases to particle precursor vapours, clusters and new aerosol particles. We will create novel measurement techniques and utilize the tremendous potential of mass spectrometry for detection of i) particle precursor vapours ii) oxidants, both conventional but also recently discovered stabilized Criegee intermediates, and, most importantly, iii) newly formed clusters. These methods and instrumentation will be applied for resolving the initial steps of new particle formation on molecular level from oxidation to clusters and stable aerosol particles. To reach these goals, targeted laboratory and field experiments together with long term field measurements will be performed employing the state-of-the-art instrumentation developed.
Principal outcomes of this project include i) new experimental methods and techniques vital for atmospheric research and a deep understanding of ii) oxidation pathways producing aerosol particle precursors, iii) the initial molecular steps of new particle formation and iv) mechanisms of growth of freshly formed clusters toward larger sizes, particularly in the crucial size range of a few nanometers. The conceptual understanding obtained during this project will open multiple new research horizons from oxidation chemistry to Earth system modeling.
Max ERC Funding
1 953 790 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym GlycoEdit
Project New Chemical Tools for Precision Glycotherapy
Researcher (PI) Thomas BOLTJE
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Country Netherlands
Call Details Starting Grant (StG), PE5, ERC-2017-STG
Summary Glycosylation, the expression of carbohydrate structures on proteins and lipids, is found in all the domains of life. The collection of all glycans found on a cell is called the “glycome” which is information rich and a key player in a plethora of physiological and pathological processes. The information that the glycome holds can be written, read and erased by glycosyltransferases, lectins and glycosidases, respectively. The immense structural complexity and the fact that glycan biosynthesis is not under direct genetic control makes it very difficult to study the glycome.
The glycosylation pattern of cancer cells is very different from that of healthy cells. It is still unclear whether aberrant glycosylation of cancer cells is a cause or consequence of tumorigenesis but it is associated with aggressive and invasive forms of cancer and hence poor prognosis. Malignant glycans are directly involved in a number of mechanisms that suppress the immune response, increase migration and extravasation (metastasis), block apoptosis and increase resistance to chemotherapy.
The aim of this proposal is develop new glycomimetics that can be used to edit the glycome of cancer cells to target such evasive mechanisms. Using combinations of new glycan based inhibitors, a coordinated attack on the cancer glycome can be carried out which is expected to severely cripple the cancers ability to grow and metastasize. This will make the tumor more susceptible to immune mediated killing which may be further enhanced in combination with other anti-cancer strategies.
To minimize systemic side effects, new methods for the local delivery/activation of glycan inhibitors will be developed. The developed methods are expected to have a much broader than just cancer alone since the studied mechanisms are also associated with autoimmune and neurodegenerative disease.
Summary
Glycosylation, the expression of carbohydrate structures on proteins and lipids, is found in all the domains of life. The collection of all glycans found on a cell is called the “glycome” which is information rich and a key player in a plethora of physiological and pathological processes. The information that the glycome holds can be written, read and erased by glycosyltransferases, lectins and glycosidases, respectively. The immense structural complexity and the fact that glycan biosynthesis is not under direct genetic control makes it very difficult to study the glycome.
The glycosylation pattern of cancer cells is very different from that of healthy cells. It is still unclear whether aberrant glycosylation of cancer cells is a cause or consequence of tumorigenesis but it is associated with aggressive and invasive forms of cancer and hence poor prognosis. Malignant glycans are directly involved in a number of mechanisms that suppress the immune response, increase migration and extravasation (metastasis), block apoptosis and increase resistance to chemotherapy.
The aim of this proposal is develop new glycomimetics that can be used to edit the glycome of cancer cells to target such evasive mechanisms. Using combinations of new glycan based inhibitors, a coordinated attack on the cancer glycome can be carried out which is expected to severely cripple the cancers ability to grow and metastasize. This will make the tumor more susceptible to immune mediated killing which may be further enhanced in combination with other anti-cancer strategies.
To minimize systemic side effects, new methods for the local delivery/activation of glycan inhibitors will be developed. The developed methods are expected to have a much broader than just cancer alone since the studied mechanisms are also associated with autoimmune and neurodegenerative disease.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym LIE ANALYSIS
Project Lie Group Analysis for Medical Image Processing
Researcher (PI) Remco Duits
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Country Netherlands
Call Details Starting Grant (StG), PE1, ERC-2013-StG
Summary The aim of this project is to substantially improve computer algorithms for image analysis in medical imaging. Currently available techniques often require significant application-specific tuning and have a limited application scope. This is mostly due to the use of non-generic feature spaces that involve many physical dimensions and lack mathematical foundation.
Instead, we derive inspiration from the superior generic pattern recognition capabilities of the human brain and propose a novel operator design aiming at better results and wider applicability.
This novel operator design combines (partial and ordinary) differential equations on non-compact Lie groups (induced by stochastic processes and sub-Riemannian geometric control) with wavelet transforms. Many mathematical challenges arise in the analysis and (numerical) solutions of these operators.
The research departs from previously developed insights of the PI on 'invertible orientation scores', which can be regarded as a specific instance in a general Lie group theoretical framework. Within this general framework one obtains a comprehensive invertible score defined on a higher dimensional Lie group beyond position space. The key challenge is to appropriately exploit these scores, their survey of multiple features per position, their underlying group structure, and their invertibility. We will tackle this via left-invariant evolutions and left-invariant sub-Riemannian optimal control within the score.
The orientation score approach will be systematically extended towards multi-scale-and-orientation, multi-velocity and multi-frequency encoding and processing, widening the application scope. Moreover, improvements in contextual enhancement via invertible scores and improvements in optimal curve extractions in the Lie group domain of the score will be pursued.
We will develop and apply the resulting algorithms to a wide range of medical imaging challenges in neurological, retinal and cardiac applications.
Summary
The aim of this project is to substantially improve computer algorithms for image analysis in medical imaging. Currently available techniques often require significant application-specific tuning and have a limited application scope. This is mostly due to the use of non-generic feature spaces that involve many physical dimensions and lack mathematical foundation.
Instead, we derive inspiration from the superior generic pattern recognition capabilities of the human brain and propose a novel operator design aiming at better results and wider applicability.
This novel operator design combines (partial and ordinary) differential equations on non-compact Lie groups (induced by stochastic processes and sub-Riemannian geometric control) with wavelet transforms. Many mathematical challenges arise in the analysis and (numerical) solutions of these operators.
The research departs from previously developed insights of the PI on 'invertible orientation scores', which can be regarded as a specific instance in a general Lie group theoretical framework. Within this general framework one obtains a comprehensive invertible score defined on a higher dimensional Lie group beyond position space. The key challenge is to appropriately exploit these scores, their survey of multiple features per position, their underlying group structure, and their invertibility. We will tackle this via left-invariant evolutions and left-invariant sub-Riemannian optimal control within the score.
The orientation score approach will be systematically extended towards multi-scale-and-orientation, multi-velocity and multi-frequency encoding and processing, widening the application scope. Moreover, improvements in contextual enhancement via invertible scores and improvements in optimal curve extractions in the Lie group domain of the score will be pursued.
We will develop and apply the resulting algorithms to a wide range of medical imaging challenges in neurological, retinal and cardiac applications.
Max ERC Funding
1 267 550 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym MEMETRE
Project From processes to modelling of methane emissions from trees
Researcher (PI) Mari PIHLATIE
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Starting Grant (StG), PE10, ERC-2017-STG
Summary Atmospheric concentration of the strong greenhouse gas methane (CH4) is rising with an increased annual growth rate. Biosphere has an important role in the global CH4 budget, but high uncertainties remain in the strength of its different sink and source components. Among the natural sources, the contribution of vegetation to the global CH4 budget is the least well understood. Role of trees to the CH4 budget of forest ecosystems has long been overlooked due to the perception that trees do not play a role in the CH4 dynamics. Methanogenic Archaea were long considered as the sole CH4 producing organisms, while new findings of aerobic CH4 production in terrestrial vegetation and in fungi show our incomplete understanding of the CH4 cycling processes. Enclosure measurements from trees reveal that trees can emit CH4 and may substantially contribute to the net CH4 exchange of forests.
The main aim of MEMETRE project is to raise the process-based understanding of CH4 exchange in boreal and temperate forests to the level where we can construct a sound process model for the soil-tree-atmosphere CH4 exchange. We will achieve this by novel laboratory and field experiment focusing on newly identified processes, quantifying CH4 fluxes, seasonal and daily variability and drivers of CH4 at leaf-level, tree and ecosystem level. We use novel CH4 flux measurement techniques to identify the roles of fungal and methanogenic production and transport mechanisms to the CH4 emission from trees, and we synthesize the experimental work to build a process model including CH4 exchange processes within trees and the soil, transport of CH4 between the soil and the trees, and transport of CH4 within the trees. The project will revolutionize our understanding of CH4 flux dynamics in forest ecosystems. It will significantly narrow down the high uncertainties in boreal and temperate forests for their contribution to the global CH4 budget.
Summary
Atmospheric concentration of the strong greenhouse gas methane (CH4) is rising with an increased annual growth rate. Biosphere has an important role in the global CH4 budget, but high uncertainties remain in the strength of its different sink and source components. Among the natural sources, the contribution of vegetation to the global CH4 budget is the least well understood. Role of trees to the CH4 budget of forest ecosystems has long been overlooked due to the perception that trees do not play a role in the CH4 dynamics. Methanogenic Archaea were long considered as the sole CH4 producing organisms, while new findings of aerobic CH4 production in terrestrial vegetation and in fungi show our incomplete understanding of the CH4 cycling processes. Enclosure measurements from trees reveal that trees can emit CH4 and may substantially contribute to the net CH4 exchange of forests.
The main aim of MEMETRE project is to raise the process-based understanding of CH4 exchange in boreal and temperate forests to the level where we can construct a sound process model for the soil-tree-atmosphere CH4 exchange. We will achieve this by novel laboratory and field experiment focusing on newly identified processes, quantifying CH4 fluxes, seasonal and daily variability and drivers of CH4 at leaf-level, tree and ecosystem level. We use novel CH4 flux measurement techniques to identify the roles of fungal and methanogenic production and transport mechanisms to the CH4 emission from trees, and we synthesize the experimental work to build a process model including CH4 exchange processes within trees and the soil, transport of CH4 between the soil and the trees, and transport of CH4 within the trees. The project will revolutionize our understanding of CH4 flux dynamics in forest ecosystems. It will significantly narrow down the high uncertainties in boreal and temperate forests for their contribution to the global CH4 budget.
Max ERC Funding
1 908 652 €
Duration
Start date: 2018-02-01, End date: 2023-01-31