Project acronym PyroPop
Project Mechanisms and regulation of inflammasome-associated programmed cell death
Researcher (PI) Mohamed Lamkanfi
Host Institution (HI) JANSSEN PHARMACEUTICA NV
Call Details Consolidator Grant (CoG), LS3, ERC-2015-CoG
Summary Programmed cell death is essential for homeostasis, and its deregulation contributes to human disease. Inflammasome-induced pyroptosis of infected macrophages contributes to host defense against infections, but the concomitant release of inflammatory danger signals and leaderless cytokines is detrimental in chronic inflammatory diseases. The central hypothesis of the PyroPop ERC Consolidator project is that inflammasomes are cytosolic platforms that couple pathogen sensing to multiple programmed cell death modes. This is based on our preliminary data showing that inflammasomes can be triggered to switch from inflammatory pyroptosis to programmed necrosis and non-inflammatory apoptosis. This suggests that the (patho)physiological outcomes of inflammasome activation may be modulated for therapeutic purposes. However, the molecular machinery and effector mechanisms of pyroptosis, inflammasome-induced apoptosis and programmed necrosis are virtually unknown. My objectives are (i) to explore the cleavage events and subcellular dynamics of pyroptosis by proteomics and high-resolution time-lapse microscopy; (ii) to clarify the molecular mechanisms of pyroptosis and inflammasome-controlled cell death switching; and (iii) to address how inflammasome-associated cell death modes impact on anti-bacterial host defense and chronic inflammatory pathology in vivo through the identification of pyroptosis-selective biomarkers and clinical analysis of pyroptosis-deficient mouse models. The central hypothesis in this regard is that inflammasome-mediated secretion of leaderless cytokines (such as IL-1β and IL-18) and danger signals may be mechanistically coupled to pyroptosis, but not apoptosis induction. By clarifying the mechanisms of inflammasome-controlled programmed cell death, this project may set the path for the development of an entirely novel class of inflammation-modulating therapies that are based on converting inflammatory pyroptosis into non-inflammatory apoptosis.
Summary
Programmed cell death is essential for homeostasis, and its deregulation contributes to human disease. Inflammasome-induced pyroptosis of infected macrophages contributes to host defense against infections, but the concomitant release of inflammatory danger signals and leaderless cytokines is detrimental in chronic inflammatory diseases. The central hypothesis of the PyroPop ERC Consolidator project is that inflammasomes are cytosolic platforms that couple pathogen sensing to multiple programmed cell death modes. This is based on our preliminary data showing that inflammasomes can be triggered to switch from inflammatory pyroptosis to programmed necrosis and non-inflammatory apoptosis. This suggests that the (patho)physiological outcomes of inflammasome activation may be modulated for therapeutic purposes. However, the molecular machinery and effector mechanisms of pyroptosis, inflammasome-induced apoptosis and programmed necrosis are virtually unknown. My objectives are (i) to explore the cleavage events and subcellular dynamics of pyroptosis by proteomics and high-resolution time-lapse microscopy; (ii) to clarify the molecular mechanisms of pyroptosis and inflammasome-controlled cell death switching; and (iii) to address how inflammasome-associated cell death modes impact on anti-bacterial host defense and chronic inflammatory pathology in vivo through the identification of pyroptosis-selective biomarkers and clinical analysis of pyroptosis-deficient mouse models. The central hypothesis in this regard is that inflammasome-mediated secretion of leaderless cytokines (such as IL-1β and IL-18) and danger signals may be mechanistically coupled to pyroptosis, but not apoptosis induction. By clarifying the mechanisms of inflammasome-controlled programmed cell death, this project may set the path for the development of an entirely novel class of inflammation-modulating therapies that are based on converting inflammatory pyroptosis into non-inflammatory apoptosis.
Max ERC Funding
1 997 915 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym QUTE
Project Quantum Tensor Networks and Entanglement
Researcher (PI) Frank Paul Bernard Verstraete
Host Institution (HI) UNIVERSITEIT GENT
Call Details Consolidator Grant (CoG), PE2, ERC-2014-CoG
Summary One of the major challenges in theoretical physics is the development of systematic methods for describing and simulating quantum many body systems with strong interactions. Given the huge experimental progress and technological potential in manipulating strongly correlated atoms and electrons, there is a pressing need for such a better theory.
The study of quantum entanglement holds the promise of being a game changer for this question. By mapping out the entanglement structure of the low-energy wavefunctions of quantum spin systems on the lattice, the prototypical example of strongly correlated systems, we have found that the associated wavefunctions can be very well modeled by a novel class of variational wavefunctions, called tensor network states. Tensor networks are changing the ways in which strongly correlated systems can be simulated, classified and understood: as opposed to the usual many body methods, these tensor networks are generic and describe non-perturbative effects in a very natural way.
The goal of this proposal is to advance the scope and use of tensor networks in several directions, both from the numerical and theoretical point of view. We plan to study the differential geometric character of the manifold of tensor network states and the associated nonlinear differential equations of motion on it, develop post tensor network methods in the form of effective theories on top of the tensor network vacuum, study tensor networks in the context of lattice gauge theories and topologically ordered systems, and investigate the novel insights that tensor networks are providing to the renormalization group and the holographic principle.
Colloquially, we believe that tensor networks and the theory of entanglement provide a basic new vocabulary for describing strongly correlated quantum systems, and the main goal of this proposal is to develop the syntax and semantics of that new language.
Summary
One of the major challenges in theoretical physics is the development of systematic methods for describing and simulating quantum many body systems with strong interactions. Given the huge experimental progress and technological potential in manipulating strongly correlated atoms and electrons, there is a pressing need for such a better theory.
The study of quantum entanglement holds the promise of being a game changer for this question. By mapping out the entanglement structure of the low-energy wavefunctions of quantum spin systems on the lattice, the prototypical example of strongly correlated systems, we have found that the associated wavefunctions can be very well modeled by a novel class of variational wavefunctions, called tensor network states. Tensor networks are changing the ways in which strongly correlated systems can be simulated, classified and understood: as opposed to the usual many body methods, these tensor networks are generic and describe non-perturbative effects in a very natural way.
The goal of this proposal is to advance the scope and use of tensor networks in several directions, both from the numerical and theoretical point of view. We plan to study the differential geometric character of the manifold of tensor network states and the associated nonlinear differential equations of motion on it, develop post tensor network methods in the form of effective theories on top of the tensor network vacuum, study tensor networks in the context of lattice gauge theories and topologically ordered systems, and investigate the novel insights that tensor networks are providing to the renormalization group and the holographic principle.
Colloquially, we believe that tensor networks and the theory of entanglement provide a basic new vocabulary for describing strongly correlated quantum systems, and the main goal of this proposal is to develop the syntax and semantics of that new language.
Max ERC Funding
1 927 500 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym RadNu
Project Radio detection of the PeV - EeV cosmic-neutrino flux
Researcher (PI) Krijn DE VRIES
Host Institution (HI) VRIJE UNIVERSITEIT BRUSSEL
Call Details Starting Grant (StG), PE9, ERC-2018-STG
Summary With the detection of the high-energy cosmic-neutrino flux by the IceCube neutrino observatory at the South-Pole, IceCube opened the field of neutrino astronomy. Nevertheless, due to the steeply falling energy spectrum, IceCube runs low in statistics at energies above a few PeV. To probe this flux at the highest energies (>PeV), therefore asks for an even larger detection volume than the cubic-kilometer currently instrumented by IceCube.
Due to its long attenuation length the radio signal is an ideal probe to cover such a large volume. When a high-energy cosmic neutrino interacts in a dense medium like ice, a relativistic particle cascade is induced. In 1962 Askaryan already predicted that due to the net charge build-up inside the cascade, coherent radio emission is expected. However, this signal is only detectable for initial neutrino energies in access of a few EeV. Therefore, currently there is a sensitivity gap to probe the high-energy cosmic neutrino flux in the PeV – EeV energy range.
This project aims to fill this sensitivity gap by the development of a novel radio detection technique to measure high-energy particle cascades in dense media, the radar detection technique. By directly probing the ionization plasma which is left behind after the neutrino induced particle cascade propagates through the medium, the radio detection energy threshold is lowered to a few PeV. The feasibility of the radar detection technique, was shown in a recent experiment. To determine the radar scattering efficiency more accurately, a new beam-test at the SLAC facility is planned as part of this proposal.
Once the scattering parameters have been determined accurately, a detailed modeling and sensitivity study will be performed to achieve the main goal of this research proposal: The construction of an in-nature experiment at the South-Pole with the sensitivity to observe 1-10 cosmic neutrino events per year in the PeV – EeV energy range.
Summary
With the detection of the high-energy cosmic-neutrino flux by the IceCube neutrino observatory at the South-Pole, IceCube opened the field of neutrino astronomy. Nevertheless, due to the steeply falling energy spectrum, IceCube runs low in statistics at energies above a few PeV. To probe this flux at the highest energies (>PeV), therefore asks for an even larger detection volume than the cubic-kilometer currently instrumented by IceCube.
Due to its long attenuation length the radio signal is an ideal probe to cover such a large volume. When a high-energy cosmic neutrino interacts in a dense medium like ice, a relativistic particle cascade is induced. In 1962 Askaryan already predicted that due to the net charge build-up inside the cascade, coherent radio emission is expected. However, this signal is only detectable for initial neutrino energies in access of a few EeV. Therefore, currently there is a sensitivity gap to probe the high-energy cosmic neutrino flux in the PeV – EeV energy range.
This project aims to fill this sensitivity gap by the development of a novel radio detection technique to measure high-energy particle cascades in dense media, the radar detection technique. By directly probing the ionization plasma which is left behind after the neutrino induced particle cascade propagates through the medium, the radio detection energy threshold is lowered to a few PeV. The feasibility of the radar detection technique, was shown in a recent experiment. To determine the radar scattering efficiency more accurately, a new beam-test at the SLAC facility is planned as part of this proposal.
Once the scattering parameters have been determined accurately, a detailed modeling and sensitivity study will be performed to achieve the main goal of this research proposal: The construction of an in-nature experiment at the South-Pole with the sensitivity to observe 1-10 cosmic neutrino events per year in the PeV – EeV energy range.
Max ERC Funding
1 410 000 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym SmartCast
Project Smart casting of concrete structures by active control of rheology
Researcher (PI) Geert De schutter
Host Institution (HI) UNIVERSITEIT GENT
Call Details Advanced Grant (AdG), PE8, ERC-2015-AdG
Summary Concrete production processes do not take full advantage of the rheological potential of fresh cementitious materials, and are still largely labour-driven and sensitive to the human factor. SmartCast proposes a new concrete casting concept to transform the concrete industry into a highly automated technological industry. Currently, the rheological properties of the concrete are defined by mix design and mixing procedure without any further active adjustment during casting. The goal of this proposal is the active control of concrete rheology during casting, and the active triggering of early stiffening of the concrete as soon as it is put in place. The ground-breaking idea to achieve this goal, is to develop concrete with actively controllable rheology by adding admixtures responsive to externally activated electromagnetic frequencies. Inter-disciplinary insights are important to achieve these goals, including inputs from concrete technology, polymer science, electrochemistry, rheology and computational fluid dynamics.
We will develop 4 new experimental test set-ups allowing to study active rheology control during different phases of the casting process: 1)concrete pumping (control of slip layer), 2)while flowing in the formwork (bulk control of rheology), 3)while flowing through formwork joints (control of formwork tightness), and 4)once the concrete is in its final position (trigger stiffening). Well-designed polymers with the desired response to the applied activation will be added to the concrete during mixing. The experiments will be analysed by advanced computational flow modelling based on fundamental rheological laws. Special attention will be paid to the compatibility of all responsive polymers selected for the different control phases. SmartCast will mean a paradigm shift for formwork-based concrete casting. The developed active rheology control will provide a fundamental basis for the development of future-proof 3D printing techniques in concrete industry
Summary
Concrete production processes do not take full advantage of the rheological potential of fresh cementitious materials, and are still largely labour-driven and sensitive to the human factor. SmartCast proposes a new concrete casting concept to transform the concrete industry into a highly automated technological industry. Currently, the rheological properties of the concrete are defined by mix design and mixing procedure without any further active adjustment during casting. The goal of this proposal is the active control of concrete rheology during casting, and the active triggering of early stiffening of the concrete as soon as it is put in place. The ground-breaking idea to achieve this goal, is to develop concrete with actively controllable rheology by adding admixtures responsive to externally activated electromagnetic frequencies. Inter-disciplinary insights are important to achieve these goals, including inputs from concrete technology, polymer science, electrochemistry, rheology and computational fluid dynamics.
We will develop 4 new experimental test set-ups allowing to study active rheology control during different phases of the casting process: 1)concrete pumping (control of slip layer), 2)while flowing in the formwork (bulk control of rheology), 3)while flowing through formwork joints (control of formwork tightness), and 4)once the concrete is in its final position (trigger stiffening). Well-designed polymers with the desired response to the applied activation will be added to the concrete during mixing. The experiments will be analysed by advanced computational flow modelling based on fundamental rheological laws. Special attention will be paid to the compatibility of all responsive polymers selected for the different control phases. SmartCast will mean a paradigm shift for formwork-based concrete casting. The developed active rheology control will provide a fundamental basis for the development of future-proof 3D printing techniques in concrete industry
Max ERC Funding
2 498 750 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym SOLCRIMET
Project Solvometallurgy for critical metals
Researcher (PI) Koen Binnemans
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Advanced Grant (AdG), PE8, ERC-2015-AdG
Summary The recent “rare-earth crisis” has brought about the widespread realisation that the long-term availability and cost stability of many materials – not just the rare earths – can no longer be guaranteed. Increasing the levels of critical metal recycling from pre-consumer, manufacturing waste and complex, multicomponent end-of-life consumer products is considered as arguably the most important and realistic mitigation strategy. However, extracting a critical metal from complex waste is a very different challenge to that faced when attempting to produce a pure metal from a primary ore deposit. SOLCRIMET therefore develops a ground-breaking, novel approach called “solvometallurgy”, a new branch within metallurgy, next to conventional hydro- and pyrometallurgy. SOLCRIMET’s aim is to successfully apply this approach to the extraction of specific critical metals, i.e. rare earths, tantalum, niobium, cobalt, indium, gallium, germanium and antimony. As these critical metals are essential components for clean-tech and high-tech applications, they are key enablers of the required transition to a low-carbon, circular economy. The approach involves the discovery of non-aqueous solvent pairs that are immiscible and allow the extraction of metal complexes at moderate temperatures, leading to high-purity recycled metals. The idea is certainly high risk, but the preliminary results already obtained are highly encouraging. The main outcomes of the project will be lab-scale demonstrators that show the enhanced efficiency, utility and applicability of the new solvometallurgical process, with respect to conventional hydro- and pyrometallurgy. SOLCRIMET’s impact on chemistry, chemical technology, metallurgy and materials engineering science will be game-changing. The possibility to recycle critical metals with energy-efficient, low-cost processes could have a significant impact on the global recycling rates of these metals.
Summary
The recent “rare-earth crisis” has brought about the widespread realisation that the long-term availability and cost stability of many materials – not just the rare earths – can no longer be guaranteed. Increasing the levels of critical metal recycling from pre-consumer, manufacturing waste and complex, multicomponent end-of-life consumer products is considered as arguably the most important and realistic mitigation strategy. However, extracting a critical metal from complex waste is a very different challenge to that faced when attempting to produce a pure metal from a primary ore deposit. SOLCRIMET therefore develops a ground-breaking, novel approach called “solvometallurgy”, a new branch within metallurgy, next to conventional hydro- and pyrometallurgy. SOLCRIMET’s aim is to successfully apply this approach to the extraction of specific critical metals, i.e. rare earths, tantalum, niobium, cobalt, indium, gallium, germanium and antimony. As these critical metals are essential components for clean-tech and high-tech applications, they are key enablers of the required transition to a low-carbon, circular economy. The approach involves the discovery of non-aqueous solvent pairs that are immiscible and allow the extraction of metal complexes at moderate temperatures, leading to high-purity recycled metals. The idea is certainly high risk, but the preliminary results already obtained are highly encouraging. The main outcomes of the project will be lab-scale demonstrators that show the enhanced efficiency, utility and applicability of the new solvometallurgical process, with respect to conventional hydro- and pyrometallurgy. SOLCRIMET’s impact on chemistry, chemical technology, metallurgy and materials engineering science will be game-changing. The possibility to recycle critical metals with energy-efficient, low-cost processes could have a significant impact on the global recycling rates of these metals.
Max ERC Funding
2 496 250 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym SpecMAT
Project Spectroscopy of exotic nuclei in a Magnetic Active Target
Researcher (PI) Riccardo Raabe
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Consolidator Grant (CoG), PE2, ERC-2013-CoG
Summary SpecMAT aims at providing crucial experimental information to answer key questions about the structure of atomic nuclei:
- What are the forces driving the shell structure in nuclei and how do they change in nuclei far from stability?
- What remains of the Z = 28 and N = 50 “magic numbers” in 78Ni?
- Do we understand shape coexistence in nuclei, and what are the mechanisms controlling its appearance?
The position of natural and “intruder” shells will be mapped in two critical regions, the neutron-rich nuclei around Z = 28 and the neutron-deficient nuclei around Z = 82. The centroids of the shell strength are derived from the complete spectroscopy of those systems in nucleon-transfer measurements. This method will be applied for the first time in the region of neutron-deficient Pb nuclei.
In SpecMAT (Spectroscopy of exotic nuclei in a Magnetic Active Target) a novel instrument will overcome the present challenges in performing such measurements with very weak beams of unstable nuclei. It combines high luminosity, high efficiency and a very large dynamic range and allows detection of both charged-particle and gamma-ray radiation. The instrument owns its remarkable performances to a number of advanced technologies concerning the use of electronics, gaseous detectors and gamma-ray detectors in a magnetic field.
The SpecMAT detector will be coupled to the HIE-ISOLDE facility for the production and post-acceleration of radioactive ion beams in construction at CERN in Geneva. HIE-ISOLDE will provide world-unique beams thanks to the use of the proton injector of the CERN complex.
If successful, SpecMAT at HIE-ISOLDE will produce specific results in nuclear structure which cannot be reached by other programmes elsewhere. Such results will have a significant impact on the present theories and models of the atomic nucleus.
Summary
SpecMAT aims at providing crucial experimental information to answer key questions about the structure of atomic nuclei:
- What are the forces driving the shell structure in nuclei and how do they change in nuclei far from stability?
- What remains of the Z = 28 and N = 50 “magic numbers” in 78Ni?
- Do we understand shape coexistence in nuclei, and what are the mechanisms controlling its appearance?
The position of natural and “intruder” shells will be mapped in two critical regions, the neutron-rich nuclei around Z = 28 and the neutron-deficient nuclei around Z = 82. The centroids of the shell strength are derived from the complete spectroscopy of those systems in nucleon-transfer measurements. This method will be applied for the first time in the region of neutron-deficient Pb nuclei.
In SpecMAT (Spectroscopy of exotic nuclei in a Magnetic Active Target) a novel instrument will overcome the present challenges in performing such measurements with very weak beams of unstable nuclei. It combines high luminosity, high efficiency and a very large dynamic range and allows detection of both charged-particle and gamma-ray radiation. The instrument owns its remarkable performances to a number of advanced technologies concerning the use of electronics, gaseous detectors and gamma-ray detectors in a magnetic field.
The SpecMAT detector will be coupled to the HIE-ISOLDE facility for the production and post-acceleration of radioactive ion beams in construction at CERN in Geneva. HIE-ISOLDE will provide world-unique beams thanks to the use of the proton injector of the CERN complex.
If successful, SpecMAT at HIE-ISOLDE will produce specific results in nuclear structure which cannot be reached by other programmes elsewhere. Such results will have a significant impact on the present theories and models of the atomic nucleus.
Max ERC Funding
1 944 900 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym SPECULOOS
Project SPECULOOS: searching for habitable planets amenable for biosignatures detection around the nearest ultra-cool stars
Researcher (PI) Michaël Gillon
Host Institution (HI) UNIVERSITE DE LIEGE
Call Details Starting Grant (StG), PE9, ERC-2013-StG
Summary "One of the most significant goals of modern astronomy is establishing whether life exists around other stars. The most direct path towards its achievement is the detection and spectroscopic characterization of terrestrial planets orbiting in the habitable zone of their host stars. The ~1000 nearest ultra-cool stars (UCS, spectral type M6 and latter) represent a unique opportunity to reach this goal within the next decade. Due to their small luminosity, their habitable zone is 30-100 times closer than for the Sun, the corresponding orbital periods ranging from one to a few days. Thanks to this proximity, the transits of habitable planets are much more probable and frequent than for Earth-Sun analogs, while the small size of UCS (~1 Jupiter radius) leads to transits deep enough for a ground-based detection, even for sub-Earth sized planets. Furthermore, habitable planets transiting nearby UCS would be amenable for a thorough atmospheric characterization with near-to-come world-class facilities, including the detection of possible biosignatures. Detecting such planets is the goal of SPECULOOS. Its instrumental concept is optimized for the detection of planets of Earth-size and below transiting the nearest Southern UCS. It consists in several robotic 1m-class telescopes equipped with new generation CCD cameras optimized for the near-IR and operating from one of the best astronomical sites of the Southern hemisphere. SPECULOOS will perform the first exploration of the Terra Incognita of planets around UCS, and detect the first terrestrial planets amenable for atmospheric characterization."
Summary
"One of the most significant goals of modern astronomy is establishing whether life exists around other stars. The most direct path towards its achievement is the detection and spectroscopic characterization of terrestrial planets orbiting in the habitable zone of their host stars. The ~1000 nearest ultra-cool stars (UCS, spectral type M6 and latter) represent a unique opportunity to reach this goal within the next decade. Due to their small luminosity, their habitable zone is 30-100 times closer than for the Sun, the corresponding orbital periods ranging from one to a few days. Thanks to this proximity, the transits of habitable planets are much more probable and frequent than for Earth-Sun analogs, while the small size of UCS (~1 Jupiter radius) leads to transits deep enough for a ground-based detection, even for sub-Earth sized planets. Furthermore, habitable planets transiting nearby UCS would be amenable for a thorough atmospheric characterization with near-to-come world-class facilities, including the detection of possible biosignatures. Detecting such planets is the goal of SPECULOOS. Its instrumental concept is optimized for the detection of planets of Earth-size and below transiting the nearest Southern UCS. It consists in several robotic 1m-class telescopes equipped with new generation CCD cameras optimized for the near-IR and operating from one of the best astronomical sites of the Southern hemisphere. SPECULOOS will perform the first exploration of the Terra Incognita of planets around UCS, and detect the first terrestrial planets amenable for atmospheric characterization."
Max ERC Funding
1 963 990 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym Sperm-Egg Phusion
Project Unexpected connections between a phagocytic machinery and mammalian fertilization
Researcher (PI) Kodimangalam Sethurama Sarma RAVICHANDRAN
Host Institution (HI) VIB
Call Details Advanced Grant (AdG), LS3, ERC-2018-ADG
Summary Fertilization is essential for a species to survive. Mammalian sexual reproduction requires the fusion between the haploid gametes sperm and egg to create a new diploid organism. Although fertilization has been studied for decades, and despite the remarkable recent discoveries of Izumo (on sperm) and Juno (on oocytes) as a critical ligand:receptor pair, due to the structure of Izumo and Juno, it is clear that other players on both the sperm and the oocytes must be involved. While the focus of our laboratory over the years has been in understanding apoptotic cell clearance by phagocytes, we accidentally noted that viable, motile, and fertilization-competent sperm exposes phosphatidylserine (PtdSer). PtdSer is a phospholipid normally exposed during apoptosis and functions as an ‘eat-me’ signal for phagocytosis. Further, masking this PtdSer on sperm inhibits fertilization in vitro. Based on additional exciting preliminary data, in this ERC proposal, we will test the hypothesis that PtdSer on viable sperm and the complementary PtdSer receptors on oocytes are key players in mammalian fertilization. We will test this at a molecular, biochemical, cellular, functional, and genetic level. From the sperm perspective — we will ask how does PtdSer changes during sperm maturation, and what molecular mechanisms regulate the exposure of PtdSer on viable sperm. From the oocyte perspective — we will test the genetic relevance of different PtdSer receptors in fertilization. From the PtdSer perspective — we will test PtdSer induces novel signals within oocytes. By combining the tools and knowledge from field of phagocytosis with tools from spermatogenesis/fertilization, this proposal integrates fields that normally do not intersect. In summary, we believe that these studies are innovative, timely, and will identify new players involved in mammalian fertilization. We expect the results of these studies to have high relevance to both male and female reproductive health and fertility.
Summary
Fertilization is essential for a species to survive. Mammalian sexual reproduction requires the fusion between the haploid gametes sperm and egg to create a new diploid organism. Although fertilization has been studied for decades, and despite the remarkable recent discoveries of Izumo (on sperm) and Juno (on oocytes) as a critical ligand:receptor pair, due to the structure of Izumo and Juno, it is clear that other players on both the sperm and the oocytes must be involved. While the focus of our laboratory over the years has been in understanding apoptotic cell clearance by phagocytes, we accidentally noted that viable, motile, and fertilization-competent sperm exposes phosphatidylserine (PtdSer). PtdSer is a phospholipid normally exposed during apoptosis and functions as an ‘eat-me’ signal for phagocytosis. Further, masking this PtdSer on sperm inhibits fertilization in vitro. Based on additional exciting preliminary data, in this ERC proposal, we will test the hypothesis that PtdSer on viable sperm and the complementary PtdSer receptors on oocytes are key players in mammalian fertilization. We will test this at a molecular, biochemical, cellular, functional, and genetic level. From the sperm perspective — we will ask how does PtdSer changes during sperm maturation, and what molecular mechanisms regulate the exposure of PtdSer on viable sperm. From the oocyte perspective — we will test the genetic relevance of different PtdSer receptors in fertilization. From the PtdSer perspective — we will test PtdSer induces novel signals within oocytes. By combining the tools and knowledge from field of phagocytosis with tools from spermatogenesis/fertilization, this proposal integrates fields that normally do not intersect. In summary, we believe that these studies are innovative, timely, and will identify new players involved in mammalian fertilization. We expect the results of these studies to have high relevance to both male and female reproductive health and fertility.
Max ERC Funding
2 499 375 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym SYDUGRAM
Project Symmetries and Dualities in Gravity and M-theory
Researcher (PI) Marc André Marie Albert Henneaux
Host Institution (HI) UNIVERSITE LIBRE DE BRUXELLES
Call Details Advanced Grant (AdG), PE2, ERC-2010-AdG_20100224
Summary Despite its considerable success, Einstein theory of gravity is an unfinished revolution: it has limitations both at the microscopic scales and at the macroscopic scales. The objective of this proposal is to provide a better understanding of the gravitational interaction beyond Einstein. This will be done by analyzing, with the aim of identifying it, the symmetry structure underlying the searched-for fundamental formulation of gravity, relying on and exploring further the intriguing and fascinating infinite-dimensional algebras uncovered recently in the study of supergravities and M-theory. One of the motivations of the project is to make progress in the development of quantum gravity, with the goal of providing new insight into black holes and cosmological singularities.
Summary
Despite its considerable success, Einstein theory of gravity is an unfinished revolution: it has limitations both at the microscopic scales and at the macroscopic scales. The objective of this proposal is to provide a better understanding of the gravitational interaction beyond Einstein. This will be done by analyzing, with the aim of identifying it, the symmetry structure underlying the searched-for fundamental formulation of gravity, relying on and exploring further the intriguing and fascinating infinite-dimensional algebras uncovered recently in the study of supergravities and M-theory. One of the motivations of the project is to make progress in the development of quantum gravity, with the goal of providing new insight into black holes and cosmological singularities.
Max ERC Funding
1 511 556 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym T-Rex
Project Clathrin-mediated endocytosis in plants: mechanistic insight into the TPLATE REcycling compleX and its interplay with AP-2
Researcher (PI) Daniel Joseph G Van Damme
Host Institution (HI) VIB
Call Details Consolidator Grant (CoG), LS3, ERC-2015-CoG
Summary Cells communicate with the outside world through proteins anchored in their plasma membrane and hereto constantly adjust their plasma membrane (PM) proteome. In this adjustment process, removing proteins from the PM mainly occurs through clathrin-mediated endocytosis (CME). Mechanistically however, this process remains poorly understood in plants.
A recent study from my group has shown that, in contrast to other model systems, plant CME involves two early endocytic adaptor protein complexes: the evolutionary conserved Adaptor Protein 2 complex (AP-2) and the newly identified TPLATE complex (TPC). In the same study, we also show that both complexes have overlapping but also independent functions in driving CME in plants, implying that plants use additional ways to recognize membrane proteins (cargo) for internalization.
In this project I will use an integrative approach to unravel the early steps of CME in plants. Specifically, I will address the following biological questions:
- Is the evolutionary retention of the TPC in plants causal to specific cargo recognition? (WP1)
- What are the spatio-temporal dynamics of TPC and CME effectors at the plasma membrane? (WP2)
- How does acute removal of TPC subunits affect complex recruitment and CME? (WP3)
- How is the TPC organized at the structural level? (WP4)
- Which interactions occur and can we couple subunit/domain structures to functionality? (WP5)
To answer these questions, I will combine state-of-the art proteomics with highly dynamic multi-color live cell imaging and structural biology.
The overall objective is to gain a deep mechanistic insight into the developmentally essential process of CME in plants. This will enable me to specifically specifically modulate the abundance of plasma membrane proteins involved in nutrient uptake, toxin avoidance, cell wall formation and hormone and defence responses. Understanding TPC-dependent CME will also provide insight into evolutionary aspects of endocytosis.
Summary
Cells communicate with the outside world through proteins anchored in their plasma membrane and hereto constantly adjust their plasma membrane (PM) proteome. In this adjustment process, removing proteins from the PM mainly occurs through clathrin-mediated endocytosis (CME). Mechanistically however, this process remains poorly understood in plants.
A recent study from my group has shown that, in contrast to other model systems, plant CME involves two early endocytic adaptor protein complexes: the evolutionary conserved Adaptor Protein 2 complex (AP-2) and the newly identified TPLATE complex (TPC). In the same study, we also show that both complexes have overlapping but also independent functions in driving CME in plants, implying that plants use additional ways to recognize membrane proteins (cargo) for internalization.
In this project I will use an integrative approach to unravel the early steps of CME in plants. Specifically, I will address the following biological questions:
- Is the evolutionary retention of the TPC in plants causal to specific cargo recognition? (WP1)
- What are the spatio-temporal dynamics of TPC and CME effectors at the plasma membrane? (WP2)
- How does acute removal of TPC subunits affect complex recruitment and CME? (WP3)
- How is the TPC organized at the structural level? (WP4)
- Which interactions occur and can we couple subunit/domain structures to functionality? (WP5)
To answer these questions, I will combine state-of-the art proteomics with highly dynamic multi-color live cell imaging and structural biology.
The overall objective is to gain a deep mechanistic insight into the developmentally essential process of CME in plants. This will enable me to specifically specifically modulate the abundance of plasma membrane proteins involved in nutrient uptake, toxin avoidance, cell wall formation and hormone and defence responses. Understanding TPC-dependent CME will also provide insight into evolutionary aspects of endocytosis.
Max ERC Funding
1 998 813 €
Duration
Start date: 2016-07-01, End date: 2021-06-30