Project acronym 2DNANOPTICA
Project Nano-optics on flatland: from quantum nanotechnology to nano-bio-photonics
Researcher (PI) Pablo Alonso-González
Host Institution (HI) UNIVERSIDAD DE OVIEDO
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary Ubiquitous in nature, light-matter interactions are of fundamental importance in science and all optical technologies. Understanding and controlling them has been a long-pursued objective in modern physics. However, so far, related experiments have relied on traditional optical schemes where, owing to the classical diffraction limit, control of optical fields to length scales below the wavelength of light is prevented. Importantly, this limitation impedes to exploit the extraordinary fundamental and scaling potentials of nanoscience and nanotechnology. A solution to concentrate optical fields into sub-diffracting volumes is the excitation of surface polaritons –coupled excitations of photons and mobile/bound charges in metals/polar materials (plasmons/phonons)-. However, their initial promises have been hindered by either strong optical losses or lack of electrical control in metals, and difficulties to fabricate high optical quality nanostructures in polar materials.
With the advent of two-dimensional (2D) materials and their extraordinary optical properties, during the last 2-3 years the visualization of both low-loss and electrically tunable (active) plasmons in graphene and high optical quality phonons in monolayer and multilayer h-BN nanostructures have been demonstrated in the mid-infrared spectral range, thus introducing a very encouraging arena for scientifically ground-breaking discoveries in nano-optics. Inspired by these extraordinary prospects, this ERC project aims to make use of our knowledge and unique expertise in 2D nanoplasmonics, and the recent advances in nanophononics, to establish a technological platform that, including coherent sources, waveguides, routers, and efficient detectors, permits an unprecedented active control and manipulation (at room temperature) of light and light-matter interactions on the nanoscale, thus laying experimentally the foundations of a 2D nano-optics field.
Summary
Ubiquitous in nature, light-matter interactions are of fundamental importance in science and all optical technologies. Understanding and controlling them has been a long-pursued objective in modern physics. However, so far, related experiments have relied on traditional optical schemes where, owing to the classical diffraction limit, control of optical fields to length scales below the wavelength of light is prevented. Importantly, this limitation impedes to exploit the extraordinary fundamental and scaling potentials of nanoscience and nanotechnology. A solution to concentrate optical fields into sub-diffracting volumes is the excitation of surface polaritons –coupled excitations of photons and mobile/bound charges in metals/polar materials (plasmons/phonons)-. However, their initial promises have been hindered by either strong optical losses or lack of electrical control in metals, and difficulties to fabricate high optical quality nanostructures in polar materials.
With the advent of two-dimensional (2D) materials and their extraordinary optical properties, during the last 2-3 years the visualization of both low-loss and electrically tunable (active) plasmons in graphene and high optical quality phonons in monolayer and multilayer h-BN nanostructures have been demonstrated in the mid-infrared spectral range, thus introducing a very encouraging arena for scientifically ground-breaking discoveries in nano-optics. Inspired by these extraordinary prospects, this ERC project aims to make use of our knowledge and unique expertise in 2D nanoplasmonics, and the recent advances in nanophononics, to establish a technological platform that, including coherent sources, waveguides, routers, and efficient detectors, permits an unprecedented active control and manipulation (at room temperature) of light and light-matter interactions on the nanoscale, thus laying experimentally the foundations of a 2D nano-optics field.
Max ERC Funding
1 459 219 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym 3D_Tryps
Project The role of three-dimensional genome architecture in antigenic variation
Researcher (PI) Tim Nicolai SIEGEL
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism.
The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression.
I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen.
The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.
Summary
Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism.
The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression.
I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen.
The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.
Max ERC Funding
1 498 175 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym ActiveBioFluids
Project Origins of Collective Motion in Active Biofluids
Researcher (PI) Daniel TAM
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
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 AlgTateGro
Project Constructing line bundles on algebraic varieties --around conjectures of Tate and Grothendieck
Researcher (PI) François CHARLES
Host Institution (HI) UNIVERSITE PARIS-SUD
Call Details Starting Grant (StG), PE1, ERC-2016-STG
Summary The goal of this project is to investigate two conjectures in arithmetic geometry pertaining to the geometry of projective varieties over finite and number fields. These two conjectures, formulated by Tate and Grothendieck in the 1960s, predict which cohomology classes are chern classes of line bundles. They both form an arithmetic counterpart of a theorem of Lefschetz, proved in the 1940s, which itself is the only known case of the Hodge conjecture. These two long-standing conjectures are one of the aspects of a more general web of questions regarding the topology of algebraic varieties which have been emphasized by Grothendieck and have since had a central role in modern arithmetic geometry. Special cases of these conjectures, appearing for instance in the work of Tate, Deligne, Faltings, Schneider-Lang, Masser-Wüstholz, have all had important consequences.
My goal is to investigate different lines of attack towards these conjectures, building on recent work on myself and Jean-Benoît Bost on related problems. The two main directions of the proposal are as follows. Over finite fields, the Tate conjecture is related to finiteness results for certain cohomological objects. I want to understand how to relate these to hidden boundedness properties of algebraic varieties that have appeared in my recent geometric proof of the Tate conjecture for K3 surfaces. The existence and relevance of a theory of Donaldson invariants for moduli spaces of twisted sheaves over finite fields seems to be a promising and novel direction. Over number fields, I want to combine the geometric insight above with algebraization techniques developed by Bost. In a joint project, we want to investigate how these can be used to first understand geometrically major results in transcendence theory and then attack the Grothendieck period conjecture for divisors via a number-theoretic and complex-analytic understanding of universal vector extensions of abelian schemes over curves.
Summary
The goal of this project is to investigate two conjectures in arithmetic geometry pertaining to the geometry of projective varieties over finite and number fields. These two conjectures, formulated by Tate and Grothendieck in the 1960s, predict which cohomology classes are chern classes of line bundles. They both form an arithmetic counterpart of a theorem of Lefschetz, proved in the 1940s, which itself is the only known case of the Hodge conjecture. These two long-standing conjectures are one of the aspects of a more general web of questions regarding the topology of algebraic varieties which have been emphasized by Grothendieck and have since had a central role in modern arithmetic geometry. Special cases of these conjectures, appearing for instance in the work of Tate, Deligne, Faltings, Schneider-Lang, Masser-Wüstholz, have all had important consequences.
My goal is to investigate different lines of attack towards these conjectures, building on recent work on myself and Jean-Benoît Bost on related problems. The two main directions of the proposal are as follows. Over finite fields, the Tate conjecture is related to finiteness results for certain cohomological objects. I want to understand how to relate these to hidden boundedness properties of algebraic varieties that have appeared in my recent geometric proof of the Tate conjecture for K3 surfaces. The existence and relevance of a theory of Donaldson invariants for moduli spaces of twisted sheaves over finite fields seems to be a promising and novel direction. Over number fields, I want to combine the geometric insight above with algebraization techniques developed by Bost. In a joint project, we want to investigate how these can be used to first understand geometrically major results in transcendence theory and then attack the Grothendieck period conjecture for divisors via a number-theoretic and complex-analytic understanding of universal vector extensions of abelian schemes over curves.
Max ERC Funding
1 222 329 €
Duration
Start date: 2016-12-01, End date: 2021-11-30
Project acronym ALLERGUT
Project Mucosal Tolerance and Allergic Predisposition: Does it all start in the gut?
Researcher (PI) Caspar OHNMACHT
Host Institution (HI) HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Currently, more than 30% of all Europeans suffer from one or more allergic disorder but treatment is still mostly symptomatic due to a lack of understanding the underlying causality. Allergies are caused by type 2 immune responses triggered by recognition of harmless antigens. Both genetic and environmental factors have been proposed to favour allergic predisposition and both factors have a huge impact on the symbiotic microbiota and the intestinal immune system. Recently we and others showed that the transcription factor ROR(γt) seems to play a key role in mucosal tolerance in the gut and also regulates intestinal type 2 immune responses.
Based on these results I postulate two major events in the gut for the development of an allergy in the lifetime of an individual: First, a failure to establish mucosal tolerance or anergy constitutes a necessity for the outbreak of allergic symptoms and allergic disease. Second, a certain ‘core’ microbiome or pathway of the intestinal microbiota predispose certain individuals for the later development of allergic disorders. Therefore, I will address the following aims:
1) Influence of ROR(γt) on mucosal tolerance induction and allergic disorders
2) Elucidate the T cell receptor repertoire of intestinal Th2 and ROR(γt)+ Tregs and assess the role of alternative NFκB pathway for induction of mucosal tolerance
3) Identification of ‘core’ microbiome signatures or metabolic pathways that favour allergic predisposition
ALLERGUT will provide ground-breaking knowledge on molecular mechanisms of the failure of mucosal tolerance in the gut and will prove if the resident ROR(γt)+ T(reg) cells can function as a mechanistic starting point for molecular intervention strategies on the background of the hygiene hypothesis. The vision of ALLERGUT is to diagnose mucosal disbalance, prevent and treat allergic disorders even before outbreak and thereby promote Public Health initiative for better living.
Summary
Currently, more than 30% of all Europeans suffer from one or more allergic disorder but treatment is still mostly symptomatic due to a lack of understanding the underlying causality. Allergies are caused by type 2 immune responses triggered by recognition of harmless antigens. Both genetic and environmental factors have been proposed to favour allergic predisposition and both factors have a huge impact on the symbiotic microbiota and the intestinal immune system. Recently we and others showed that the transcription factor ROR(γt) seems to play a key role in mucosal tolerance in the gut and also regulates intestinal type 2 immune responses.
Based on these results I postulate two major events in the gut for the development of an allergy in the lifetime of an individual: First, a failure to establish mucosal tolerance or anergy constitutes a necessity for the outbreak of allergic symptoms and allergic disease. Second, a certain ‘core’ microbiome or pathway of the intestinal microbiota predispose certain individuals for the later development of allergic disorders. Therefore, I will address the following aims:
1) Influence of ROR(γt) on mucosal tolerance induction and allergic disorders
2) Elucidate the T cell receptor repertoire of intestinal Th2 and ROR(γt)+ Tregs and assess the role of alternative NFκB pathway for induction of mucosal tolerance
3) Identification of ‘core’ microbiome signatures or metabolic pathways that favour allergic predisposition
ALLERGUT will provide ground-breaking knowledge on molecular mechanisms of the failure of mucosal tolerance in the gut and will prove if the resident ROR(γt)+ T(reg) cells can function as a mechanistic starting point for molecular intervention strategies on the background of the hygiene hypothesis. The vision of ALLERGUT is to diagnose mucosal disbalance, prevent and treat allergic disorders even before outbreak and thereby promote Public Health initiative for better living.
Max ERC Funding
1 498 175 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym AQSuS
Project Analog Quantum Simulation using Superconducting Qubits
Researcher (PI) Gerhard KIRCHMAIR
Host Institution (HI) UNIVERSITAET INNSBRUCK
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary AQSuS aims at experimentally implementing analogue quantum simulation of interacting spin models in two-dimensional geometries. The proposed experimental approach paves the way to investigate a broad range of currently inaccessible quantum phenomena, for which existing analytical and numerical methods reach their limitations. Developing precisely controlled interacting quantum systems in 2D is an important current goal well beyond the field of quantum simulation and has applications in e.g. solid state physics, computing and metrology.
To access these models, I propose to develop a novel circuit quantum-electrodynamics (cQED) platform based on the 3D transmon qubit architecture. This platform utilizes the highly engineerable properties and long coherence times of these qubits. A central novel idea behind AQSuS is to exploit the spatial dependence of the naturally occurring dipolar interactions between the qubits to engineer the desired spin-spin interactions. This approach avoids the complicated wiring, typical for other cQED experiments and reduces the complexity of the experimental setup. The scheme is therefore directly scalable to larger systems. The experimental goals are:
1) Demonstrate analogue quantum simulation of an interacting spin system in 1D & 2D.
2) Establish methods to precisely initialize the state of the system, control the interactions and readout single qubit states and multi-qubit correlations.
3) Investigate unobserved quantum phenomena on 2D geometries e.g. kagome and triangular lattices.
4) Study open system dynamics with interacting spin systems.
AQSuS builds on my backgrounds in both superconducting qubits and quantum simulation with trapped-ions. With theory collaborators my young research group and I have recently published an article in PRB [9] describing and analysing the proposed platform. The ERC starting grant would allow me to open a big new research direction and capitalize on the foundations established over the last two years.
Summary
AQSuS aims at experimentally implementing analogue quantum simulation of interacting spin models in two-dimensional geometries. The proposed experimental approach paves the way to investigate a broad range of currently inaccessible quantum phenomena, for which existing analytical and numerical methods reach their limitations. Developing precisely controlled interacting quantum systems in 2D is an important current goal well beyond the field of quantum simulation and has applications in e.g. solid state physics, computing and metrology.
To access these models, I propose to develop a novel circuit quantum-electrodynamics (cQED) platform based on the 3D transmon qubit architecture. This platform utilizes the highly engineerable properties and long coherence times of these qubits. A central novel idea behind AQSuS is to exploit the spatial dependence of the naturally occurring dipolar interactions between the qubits to engineer the desired spin-spin interactions. This approach avoids the complicated wiring, typical for other cQED experiments and reduces the complexity of the experimental setup. The scheme is therefore directly scalable to larger systems. The experimental goals are:
1) Demonstrate analogue quantum simulation of an interacting spin system in 1D & 2D.
2) Establish methods to precisely initialize the state of the system, control the interactions and readout single qubit states and multi-qubit correlations.
3) Investigate unobserved quantum phenomena on 2D geometries e.g. kagome and triangular lattices.
4) Study open system dynamics with interacting spin systems.
AQSuS builds on my backgrounds in both superconducting qubits and quantum simulation with trapped-ions. With theory collaborators my young research group and I have recently published an article in PRB [9] describing and analysing the proposed platform. The ERC starting grant would allow me to open a big new research direction and capitalize on the foundations established over the last two years.
Max ERC Funding
1 498 515 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym ATOM
Project Advanced Holographic Tomographies for Nanoscale Materials: Revealing Electromagnetic and Deformation Fields, Chemical Composition and Quantum States at Atomic Resolution.
Researcher (PI) Axel LUBK
Host Institution (HI) LEIBNIZ-INSTITUT FUER FESTKOERPER- UND WERKSTOFFFORSCHUNG DRESDEN E.V.
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary The ongoing miniaturization in nanotechnology and functional materials puts an ever increasing focus on the development of three-dimensional (3D) nanostructures, such as quantum dot arrays, structured nanowires, or non-trivial topological magnetic textures such as skyrmions, which permit a better performance of logical or memory devices in terms of speed and energy efficiency. To develop and advance such technologies and to improve the understanding of the underlying fundamental solid state physics effects, the nondestructive and quantitative 3D characterization of physical, e.g., electric or magnetic, fields down to atomic resolution is indispensable. Current nanoscale metrology methods only inadequately convey this information, e.g., because they probe surfaces, record projections, or lack resolution. AToM will provide a ground-breaking tomographic methodology for current nanotechnology by mapping electric and magnetic fields as well as crucial properties of the underlying atomic structure in solids, such as the chemical composition, mechanical strain or spin configuration in 3D down to atomic resolution. To achieve that goal, advanced holographic and tomographic setups in the Transmission Electron Microscope (TEM) are combined with novel computational methods, e.g., taking into account the ramifications of electron diffraction. Moreover, fundamental application limits are overcome (A) by extending the holographic principle, requiring coherent electron beams, to quantum state reconstructions applicable to electrons of any (in)coherence; and (B) by adapting a unique in-situ TEM with a very large sample chamber to facilitate holographic field sensing down to very low temperatures (6 K) under application of external, e.g., electric, stimuli. The joint development of AToM in response to current problems of nanotechnology, including the previously mentioned ones, is anticipated to immediately and sustainably advance nanotechnology in its various aspects.
Summary
The ongoing miniaturization in nanotechnology and functional materials puts an ever increasing focus on the development of three-dimensional (3D) nanostructures, such as quantum dot arrays, structured nanowires, or non-trivial topological magnetic textures such as skyrmions, which permit a better performance of logical or memory devices in terms of speed and energy efficiency. To develop and advance such technologies and to improve the understanding of the underlying fundamental solid state physics effects, the nondestructive and quantitative 3D characterization of physical, e.g., electric or magnetic, fields down to atomic resolution is indispensable. Current nanoscale metrology methods only inadequately convey this information, e.g., because they probe surfaces, record projections, or lack resolution. AToM will provide a ground-breaking tomographic methodology for current nanotechnology by mapping electric and magnetic fields as well as crucial properties of the underlying atomic structure in solids, such as the chemical composition, mechanical strain or spin configuration in 3D down to atomic resolution. To achieve that goal, advanced holographic and tomographic setups in the Transmission Electron Microscope (TEM) are combined with novel computational methods, e.g., taking into account the ramifications of electron diffraction. Moreover, fundamental application limits are overcome (A) by extending the holographic principle, requiring coherent electron beams, to quantum state reconstructions applicable to electrons of any (in)coherence; and (B) by adapting a unique in-situ TEM with a very large sample chamber to facilitate holographic field sensing down to very low temperatures (6 K) under application of external, e.g., electric, stimuli. The joint development of AToM in response to current problems of nanotechnology, including the previously mentioned ones, is anticipated to immediately and sustainably advance nanotechnology in its various aspects.
Max ERC Funding
1 499 602 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym Baby DCs
Project Age-dependent Regulation of Dendritic Cell Development and Function
Researcher (PI) Barbara Ursula SCHRAML
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Early life immune balance is essential for survival and establishment of healthy immunity in later life. We aim to define how age-dependent regulation of dendritic cell (DC) development contributes to this crucial immune balance. DCs are versatile controllers of immunity that in neonates are qualitatively distinct from adults. Why such age-dependent differences exist is unclear but newborn DCs are considered underdeveloped and functionally immature.
Using ontogenetic tracing of conventional DC precursors, I have found a previously unappreciated developmental heterogeneity of DCs that is particularly prominent in young mice. Preliminary data indicate that distinct waves of DC poiesis contribute to the functional differences between neonatal and adult DCs. I hypothesize that the neonatal DC compartment is not immature but rather that DC poiesis is developmentally regulated to create essential age-dependent immune balance. Further, I have identified a unique situation in early life to address a fundamental biological question, namely to what extent cellular function is pre-programmed by developmental origin (nature) versus environmental factors (nurture).
In this proposal, we will first use novel models to fate map the origin of the DC compartment with age. We will then define to what extent cellular origin determines age-dependent functions of DCs in immunity. Using innovative comparative gene expression profiling and integrative epigenomic analysis the cell intrinsic mechanisms regulating the age-dependent functions of DCs will be characterized. Because environmental factors in utero and after birth critically influence immune balance, we will finally define the impact of maternal infection and metabolic disease, as well as early microbial encounter on DC poiesis. Characterizing how developmentally regulated DC poiesis shapes the unique features of early life immunity will provide novel insights into immune development that are vital to advance vaccine strategies.
Summary
Early life immune balance is essential for survival and establishment of healthy immunity in later life. We aim to define how age-dependent regulation of dendritic cell (DC) development contributes to this crucial immune balance. DCs are versatile controllers of immunity that in neonates are qualitatively distinct from adults. Why such age-dependent differences exist is unclear but newborn DCs are considered underdeveloped and functionally immature.
Using ontogenetic tracing of conventional DC precursors, I have found a previously unappreciated developmental heterogeneity of DCs that is particularly prominent in young mice. Preliminary data indicate that distinct waves of DC poiesis contribute to the functional differences between neonatal and adult DCs. I hypothesize that the neonatal DC compartment is not immature but rather that DC poiesis is developmentally regulated to create essential age-dependent immune balance. Further, I have identified a unique situation in early life to address a fundamental biological question, namely to what extent cellular function is pre-programmed by developmental origin (nature) versus environmental factors (nurture).
In this proposal, we will first use novel models to fate map the origin of the DC compartment with age. We will then define to what extent cellular origin determines age-dependent functions of DCs in immunity. Using innovative comparative gene expression profiling and integrative epigenomic analysis the cell intrinsic mechanisms regulating the age-dependent functions of DCs will be characterized. Because environmental factors in utero and after birth critically influence immune balance, we will finally define the impact of maternal infection and metabolic disease, as well as early microbial encounter on DC poiesis. Characterizing how developmentally regulated DC poiesis shapes the unique features of early life immunity will provide novel insights into immune development that are vital to advance vaccine strategies.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym CASe
Project Combinatorics with an analytic structure
Researcher (PI) Karim ADIPRASITO
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), PE1, ERC-2016-STG
Summary "Combinatorics, and its interplay with geometry, has fascinated our ancestors as shown by early stone carvings in the Neolithic period. Modern combinatorics is motivated by the ubiquity of its structures in both pure and applied mathematics.
The work of Hochster and Stanley, who realized the relation of enumerative questions to commutative algebra and toric geometry made a vital contribution to the development of this subject. Their work was a central contribution to the classification of face numbers of simple polytopes, and the initial success lead to a wealth of research in which combinatorial problems were translated to algebra and geometry and then solved using deep results such as Saito's hard Lefschetz theorem. As a caveat, this also made branches of combinatorics reliant on algebra and geometry to provide new ideas.
In this proposal, I want to reverse this approach and extend our understanding of geometry and algebra guided by combinatorial methods. In this spirit I propose new combinatorial approaches to the interplay of curvature and topology, to isoperimetry, geometric analysis, and intersection theory, to name a few. In addition, while these subjects are interesting by themselves, they are also designed to advance classical topics, for example, the diameter of polyhedra (as in the Hirsch conjecture), arrangement theory (and the study of arrangement complements), Hodge theory (as in Grothendieck's standard conjectures), and realization problems of discrete objects (as in Connes embedding problem for type II factors).
This proposal is supported by the review of some already developed tools, such as relative Stanley--Reisner theory (which is equipped to deal with combinatorial isoperimetries), combinatorial Hodge theory (which extends the ``K\""ahler package'' to purely combinatorial settings), and discrete PDEs (which were used to construct counterexamples to old problems in discrete geometry)."
Summary
"Combinatorics, and its interplay with geometry, has fascinated our ancestors as shown by early stone carvings in the Neolithic period. Modern combinatorics is motivated by the ubiquity of its structures in both pure and applied mathematics.
The work of Hochster and Stanley, who realized the relation of enumerative questions to commutative algebra and toric geometry made a vital contribution to the development of this subject. Their work was a central contribution to the classification of face numbers of simple polytopes, and the initial success lead to a wealth of research in which combinatorial problems were translated to algebra and geometry and then solved using deep results such as Saito's hard Lefschetz theorem. As a caveat, this also made branches of combinatorics reliant on algebra and geometry to provide new ideas.
In this proposal, I want to reverse this approach and extend our understanding of geometry and algebra guided by combinatorial methods. In this spirit I propose new combinatorial approaches to the interplay of curvature and topology, to isoperimetry, geometric analysis, and intersection theory, to name a few. In addition, while these subjects are interesting by themselves, they are also designed to advance classical topics, for example, the diameter of polyhedra (as in the Hirsch conjecture), arrangement theory (and the study of arrangement complements), Hodge theory (as in Grothendieck's standard conjectures), and realization problems of discrete objects (as in Connes embedding problem for type II factors).
This proposal is supported by the review of some already developed tools, such as relative Stanley--Reisner theory (which is equipped to deal with combinatorial isoperimetries), combinatorial Hodge theory (which extends the ``K\""ahler package'' to purely combinatorial settings), and discrete PDEs (which were used to construct counterexamples to old problems in discrete geometry)."
Max ERC Funding
1 337 200 €
Duration
Start date: 2016-12-01, End date: 2021-11-30
Project acronym CC4SOL
Project Towards chemical accuracy in computational materials science
Researcher (PI) Andreas GRÜNEIS
Host Institution (HI) TECHNISCHE UNIVERSITAET WIEN
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary This project aims at the development of a novel toolbox of ab-initio methods that approximate the true many-electron wavefunction using systematically improvable perturbation and coupled-cluster theories. The demand and prospects for these methods are excellent given that the highly-accurate coupled-cluster theories can predict atomization- and reaction energies in a wide range of solids and molecules with chemical accuracy (≈43 meV). However, the computational cost involved inhibits their widespread use in the field of materials science so far. A multitude of suggested developments in the present proposal hold the promise to reduce the computational cost beyond what is currently considered possible by the community. These include explicit correlation methods that augment the conventional wavefunction expansion with terms that depend on the electron pair correlation factors. In contrast to the widely-used homogeneous correlation factors, this proposal aims at the investigation of inhomogeneous correlation factors that can also capture van der Waals interactions. Furthermore this proposal seeks to employ a recently developed combination of atom-centered basis functions and plane wave basis sets, maximizing the compactness in the wavefunction expansion. The combination of these ideas bears the potential to reduce the computational cost of coupled-cluster calculations in solids by three orders of magnitude, leading to a breakthrough in the field of highly-accurate ab-initio simulations. As such the study of challenging solid state physics and chemistry problems forms an important part of this proposal. We seek to investigate molecular adsorption and reactions in zeolites and on surfaces, pressure-driven solid-solid phase transitions of two dimensional layered materials and defects in solids. These problems are paradigmatic for van der Waals interactions and strong correlation, and methods that describe their electronic structure accurately are highly sought after.
Summary
This project aims at the development of a novel toolbox of ab-initio methods that approximate the true many-electron wavefunction using systematically improvable perturbation and coupled-cluster theories. The demand and prospects for these methods are excellent given that the highly-accurate coupled-cluster theories can predict atomization- and reaction energies in a wide range of solids and molecules with chemical accuracy (≈43 meV). However, the computational cost involved inhibits their widespread use in the field of materials science so far. A multitude of suggested developments in the present proposal hold the promise to reduce the computational cost beyond what is currently considered possible by the community. These include explicit correlation methods that augment the conventional wavefunction expansion with terms that depend on the electron pair correlation factors. In contrast to the widely-used homogeneous correlation factors, this proposal aims at the investigation of inhomogeneous correlation factors that can also capture van der Waals interactions. Furthermore this proposal seeks to employ a recently developed combination of atom-centered basis functions and plane wave basis sets, maximizing the compactness in the wavefunction expansion. The combination of these ideas bears the potential to reduce the computational cost of coupled-cluster calculations in solids by three orders of magnitude, leading to a breakthrough in the field of highly-accurate ab-initio simulations. As such the study of challenging solid state physics and chemistry problems forms an important part of this proposal. We seek to investigate molecular adsorption and reactions in zeolites and on surfaces, pressure-driven solid-solid phase transitions of two dimensional layered materials and defects in solids. These problems are paradigmatic for van der Waals interactions and strong correlation, and methods that describe their electronic structure accurately are highly sought after.
Max ERC Funding
1 460 826 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
