Project acronym BABE
Project Why is the world green: testing top-down control of plant-herbivore food webs by experiments with birds, bats and ants
Researcher (PI) Katerina SAM
Host Institution (HI) Biologicke centrum AV CR, v. v. i.
Call Details Starting Grant (StG), LS8, ERC-2018-STG
Summary Why is the world green? Because predators control herbivores, allowing plants to flourish. This >50 years old answer to the deceptively simple question remains controversial. After all, plants are also protected from herbivores physically and by secondary chemistry. My goal is to test novel aspects of the “green world hypothesis”: ● How the importance of top-down effects varies with forest diversity and productivity along a latitudinal gradient? ● How the key predators, birds, bats and ants, contribute to top-down effects individually and in synergy? I strive to understand this because: ● While there is evidence that predators reduce herbivore abundance and enhance plant growth, the importance of top-down control is poorly understood across a range of forests. ● The importance of key predatory groups, and their antagonistic and synergic interactions, have been rarely studied, despite their potential impact on ecosystem dynamics in changing world. I wish to achieve my goals by: ● Factorial manipulations of key insectivorous predators (birds, bats, ants) to measure their effects on lower trophic levels in forest understories and canopies, accessed by canopy cranes, along latitudinal gradient spanning 75o from Australia to Japan. ● Studying compensatory effects among predatory taxa on herbivore and plant performance. Why this has not been done before: ● Factorial experimental exclusion of predatory groups replicated on a large spatial scale is logistically difficult. ● Canopy crane network along a latitudinal gradient has only recently become available. I am in excellent position to succeed as I have experience with ● foodweb experiments along an elevation gradient in New Guinea rainforests, ● study of bird, bat and arthropod communities. If the project is successful, it will: ● Allow understanding the importance of predators from temperate to tropical forests. ● Establish a network of experimental sites along a network of canopy cranes open for follow-up research.
Summary
Why is the world green? Because predators control herbivores, allowing plants to flourish. This >50 years old answer to the deceptively simple question remains controversial. After all, plants are also protected from herbivores physically and by secondary chemistry. My goal is to test novel aspects of the “green world hypothesis”: ● How the importance of top-down effects varies with forest diversity and productivity along a latitudinal gradient? ● How the key predators, birds, bats and ants, contribute to top-down effects individually and in synergy? I strive to understand this because: ● While there is evidence that predators reduce herbivore abundance and enhance plant growth, the importance of top-down control is poorly understood across a range of forests. ● The importance of key predatory groups, and their antagonistic and synergic interactions, have been rarely studied, despite their potential impact on ecosystem dynamics in changing world. I wish to achieve my goals by: ● Factorial manipulations of key insectivorous predators (birds, bats, ants) to measure their effects on lower trophic levels in forest understories and canopies, accessed by canopy cranes, along latitudinal gradient spanning 75o from Australia to Japan. ● Studying compensatory effects among predatory taxa on herbivore and plant performance. Why this has not been done before: ● Factorial experimental exclusion of predatory groups replicated on a large spatial scale is logistically difficult. ● Canopy crane network along a latitudinal gradient has only recently become available. I am in excellent position to succeed as I have experience with ● foodweb experiments along an elevation gradient in New Guinea rainforests, ● study of bird, bat and arthropod communities. If the project is successful, it will: ● Allow understanding the importance of predators from temperate to tropical forests. ● Establish a network of experimental sites along a network of canopy cranes open for follow-up research.
Max ERC Funding
1 455 032 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
Project acronym Cat-In-hAT
Project Catastrophic Interactions of Binary Stars and the Associated Transients
Researcher (PI) Ondrej PEJCHA
Host Institution (HI) UNIVERZITA KARLOVA
Call Details Starting Grant (StG), PE9, ERC-2018-STG
Summary "One of the crucial formation channels of compact object binaries, including sources of gravitational waves, critically depends on catastrophic binary interactions accompanied by the loss of mass, angular momentum, and energy (""common envelope"" evolution - CEE). Despite its importance, CEE is perhaps the least understood major phase of binary star evolution and progress in this area is urgently needed to interpret observations from the new facilities (gravitational wave detectors, time-domain surveys).
Recently, the dynamical phase of the CEE has been associated with a class of transient brightenings exhibiting slow expansion velocities and copious formation of dust and molecules (red transients - RT). A number of RT features, especially the long timescale of mass loss, challenge the existing CEE paradigm.
Motivated by RT, I will use a new variant of magnetohydrodynamics to comprehensively examine the 3D evolution of CEE from the moment when the mass loss commences to the remnant phase. I expect to resolve the long timescales observed in RT, characterize binary stability in 3D with detailed microphysics, illuminate the fundamental problem of how is orbital energy used to unbind the common envelope in a regime that was inaccessible before, and break new ground on the amplification of magnetic fields during CEE.
I will establish RT as an entirely new probe of the CEE physics by comparing my detailed theoretical predictions of light curves from different viewing angles, spectra, line profiles, and polarimetric signatures with observations of RT. I will accomplish this by coupling multi-dimensional moving mesh hydrodynamics with radiation, dust formation, and chemical reactions. Finally, I will examine the physical processes in RT remnants on timescales of years to centuries after the outburst to connect RT with the proposed merger products and to identify them in time-domain surveys.
"
Summary
"One of the crucial formation channels of compact object binaries, including sources of gravitational waves, critically depends on catastrophic binary interactions accompanied by the loss of mass, angular momentum, and energy (""common envelope"" evolution - CEE). Despite its importance, CEE is perhaps the least understood major phase of binary star evolution and progress in this area is urgently needed to interpret observations from the new facilities (gravitational wave detectors, time-domain surveys).
Recently, the dynamical phase of the CEE has been associated with a class of transient brightenings exhibiting slow expansion velocities and copious formation of dust and molecules (red transients - RT). A number of RT features, especially the long timescale of mass loss, challenge the existing CEE paradigm.
Motivated by RT, I will use a new variant of magnetohydrodynamics to comprehensively examine the 3D evolution of CEE from the moment when the mass loss commences to the remnant phase. I expect to resolve the long timescales observed in RT, characterize binary stability in 3D with detailed microphysics, illuminate the fundamental problem of how is orbital energy used to unbind the common envelope in a regime that was inaccessible before, and break new ground on the amplification of magnetic fields during CEE.
I will establish RT as an entirely new probe of the CEE physics by comparing my detailed theoretical predictions of light curves from different viewing angles, spectra, line profiles, and polarimetric signatures with observations of RT. I will accomplish this by coupling multi-dimensional moving mesh hydrodynamics with radiation, dust formation, and chemical reactions. Finally, I will examine the physical processes in RT remnants on timescales of years to centuries after the outburst to connect RT with the proposed merger products and to identify them in time-domain surveys.
"
Max ERC Funding
1 243 219 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym CELLONGATE
Project Unraveling the molecular network that drives cell growth in plants
Researcher (PI) Matyas FENDRYCH
Host Institution (HI) UNIVERZITA KARLOVA
Call Details Starting Grant (StG), LS3, ERC-2018-STG
Summary Plants differ strikingly from animals by the almost total absence of cell migration in their development. Plants build their bodies using a hydrostatic skeleton that consists of pressurized cells encased by a cell wall. Consequently, plant cells cannot migrate and must sculpture their bodies by orientation of cell division and precise regulation of cell growth. Cell growth depends on the balance between internal cell pressure – turgor, and strength of the cell wall. Cell growth is under a strict developmental control, which is exemplified in the Arabidopsis thaliana root tip, where massive cell elongation occurs in a defined spatio-temporal developmental window. Despite the immobility of their cells, plant organs move to optimize light and nutrient acquisition and to orient their bodies along the gravity vector. These movements depend on differential regulation of cell elongation across the organ, and on response to the phytohormone auxin. Even though the control of cell growth is in the epicenter of plant development, protein networks steering the developmental growth onset, coordination and termination remain elusive. Similarly, although auxin is the central regulator of growth, the molecular mechanism of its effect on root growth is unknown. In this project, I will establish a unique microscopy setup for high spatio-temporal resolution live-cell imaging equipped with a microfluidic lab-on-chip platform optimized for growing roots, to enable analysis and manipulation of root growth physiology. I will use developmental gradients in the root to discover genes that steer cellular growth, by correlating transcriptome profiles of individual cell types with the cell size. In parallel, I will exploit the auxin effect on root to unravel molecular mechanisms that control cell elongation. Finally, I am going to combine the live-cell imaging methodology with the gene discovery approaches to chart a dynamic spatio-temporal physiological map of a growing Arabidopsis root.
Summary
Plants differ strikingly from animals by the almost total absence of cell migration in their development. Plants build their bodies using a hydrostatic skeleton that consists of pressurized cells encased by a cell wall. Consequently, plant cells cannot migrate and must sculpture their bodies by orientation of cell division and precise regulation of cell growth. Cell growth depends on the balance between internal cell pressure – turgor, and strength of the cell wall. Cell growth is under a strict developmental control, which is exemplified in the Arabidopsis thaliana root tip, where massive cell elongation occurs in a defined spatio-temporal developmental window. Despite the immobility of their cells, plant organs move to optimize light and nutrient acquisition and to orient their bodies along the gravity vector. These movements depend on differential regulation of cell elongation across the organ, and on response to the phytohormone auxin. Even though the control of cell growth is in the epicenter of plant development, protein networks steering the developmental growth onset, coordination and termination remain elusive. Similarly, although auxin is the central regulator of growth, the molecular mechanism of its effect on root growth is unknown. In this project, I will establish a unique microscopy setup for high spatio-temporal resolution live-cell imaging equipped with a microfluidic lab-on-chip platform optimized for growing roots, to enable analysis and manipulation of root growth physiology. I will use developmental gradients in the root to discover genes that steer cellular growth, by correlating transcriptome profiles of individual cell types with the cell size. In parallel, I will exploit the auxin effect on root to unravel molecular mechanisms that control cell elongation. Finally, I am going to combine the live-cell imaging methodology with the gene discovery approaches to chart a dynamic spatio-temporal physiological map of a growing Arabidopsis root.
Max ERC Funding
1 498 750 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym CerQuS
Project Certified Quantum Security
Researcher (PI) Dominique Peer Ghislain UNRUH
Host Institution (HI) TARTU ULIKOOL
Call Details Consolidator Grant (CoG), PE6, ERC-2018-COG
Summary "Digital communication permeates all areas of today's daily life. Cryptographic protocols are used to secure that
communication. Quantum communication and the advent of quantum computers both threaten existing cryptographic
solutions, and create new opportunities for secure protocols. The security of cryptographic systems is normally ensured by
mathematical proofs. Due to human error, however, these proofs often contain errors, limiting the usefulness of said proofs.
This is especially true in the case of quantum protocols since human intuition is well-adapted to the classical world, but not
to quantum mechanics. To resolve this problem, methods for verifying cryptographic security proofs using computers (i.e.,
for ""certifying"" the security) have been developed. Yet, all existing verification approaches handle classical cryptography
only - for quantum protocols, no approaches exist.
This project will lay the foundations for the verification of quantum cryptography. We will design logics and software tools
for developing and verifying security proofs on the computer, both for classical protocols secure against quantum computer
(post-quantum security) and for protocols that use quantum communication.
Our main approach is the design of a logic (quantum relational Hoare logic, qRHL) for reasoning about the relationship
between pairs of quantum programs, together with an ecosystem of manual and automated reasoning tools, culminating in
fully certified security proofs for real-world quantum protocols.
As a final result, the project will improve the security of protocols in the quantum age, by removing one possible source of
human error. In addition, the project directly impacts the research community, by providing new foundations in program
verification, and by providing cryptographers with new tools for the verification of their protocols.
"
Summary
"Digital communication permeates all areas of today's daily life. Cryptographic protocols are used to secure that
communication. Quantum communication and the advent of quantum computers both threaten existing cryptographic
solutions, and create new opportunities for secure protocols. The security of cryptographic systems is normally ensured by
mathematical proofs. Due to human error, however, these proofs often contain errors, limiting the usefulness of said proofs.
This is especially true in the case of quantum protocols since human intuition is well-adapted to the classical world, but not
to quantum mechanics. To resolve this problem, methods for verifying cryptographic security proofs using computers (i.e.,
for ""certifying"" the security) have been developed. Yet, all existing verification approaches handle classical cryptography
only - for quantum protocols, no approaches exist.
This project will lay the foundations for the verification of quantum cryptography. We will design logics and software tools
for developing and verifying security proofs on the computer, both for classical protocols secure against quantum computer
(post-quantum security) and for protocols that use quantum communication.
Our main approach is the design of a logic (quantum relational Hoare logic, qRHL) for reasoning about the relationship
between pairs of quantum programs, together with an ecosystem of manual and automated reasoning tools, culminating in
fully certified security proofs for real-world quantum protocols.
As a final result, the project will improve the security of protocols in the quantum age, by removing one possible source of
human error. In addition, the project directly impacts the research community, by providing new foundations in program
verification, and by providing cryptographers with new tools for the verification of their protocols.
"
Max ERC Funding
1 716 475 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym FunDiT
Project Functional Diversity of T cells
Researcher (PI) Ondrej STEPANEK
Host Institution (HI) USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE
Call Details Starting Grant (StG), LS6, ERC-2018-STG
Summary T cells have a central role in most adaptive immune responses, including immunity to infection, cancer, and autoimmunity. Increasing evidence shows that even resting steady-state T cells form many different subsets with unique functions. Variable level of self-reactivity and previous antigenic exposure are most likely two major determinants of the T-cell diversity. However, the number, identity, and biological function of steady-state T-cell subsets are still very incompletely understood. Receptors to ligands from TNF and B7 families exhibit variable expression among T-cell subsets and are important regulators of T-cell fate decisions. We hypothesize that pathways triggered by these receptors substantially contribute to the functional diversity of T cells.The FunDiT project uses a set of novel tools to systematically identify steady-state CD8+ T cell subsets and characterize their biological roles. The project has three complementary objectives.
(1) Identification of CD8+ T cell subsets. We will identify subsets based on single cell gene expression profiling. We will determine the role of self and foreign antigens in the formation of these subsets and match corresponding subsets between mice and humans.
(2) Role of particular subsets in the immune response. We will compare antigenic responses of particular subsets using our novel model allowing inducible expression of a defined TCR. The activity of T-cell subsets in three disease models (infection, cancer, autoimmunity) will be characterized.
(3) Characterization of key costimulatory/inhibitory pathways. We will use our novel mass spectrometry-based approach to identify receptors and signaling molecules involved in the signaling by ligands from TNF and B7 families in T cells.
The results will provide understanding of the adaptive immunity in particular disease context and resolve long-standing questions concerning the roles of T-cell diversity in protective immunity and tolerance to healthy tissues and tumors.
Summary
T cells have a central role in most adaptive immune responses, including immunity to infection, cancer, and autoimmunity. Increasing evidence shows that even resting steady-state T cells form many different subsets with unique functions. Variable level of self-reactivity and previous antigenic exposure are most likely two major determinants of the T-cell diversity. However, the number, identity, and biological function of steady-state T-cell subsets are still very incompletely understood. Receptors to ligands from TNF and B7 families exhibit variable expression among T-cell subsets and are important regulators of T-cell fate decisions. We hypothesize that pathways triggered by these receptors substantially contribute to the functional diversity of T cells.The FunDiT project uses a set of novel tools to systematically identify steady-state CD8+ T cell subsets and characterize their biological roles. The project has three complementary objectives.
(1) Identification of CD8+ T cell subsets. We will identify subsets based on single cell gene expression profiling. We will determine the role of self and foreign antigens in the formation of these subsets and match corresponding subsets between mice and humans.
(2) Role of particular subsets in the immune response. We will compare antigenic responses of particular subsets using our novel model allowing inducible expression of a defined TCR. The activity of T-cell subsets in three disease models (infection, cancer, autoimmunity) will be characterized.
(3) Characterization of key costimulatory/inhibitory pathways. We will use our novel mass spectrometry-based approach to identify receptors and signaling molecules involved in the signaling by ligands from TNF and B7 families in T cells.
The results will provide understanding of the adaptive immunity in particular disease context and resolve long-standing questions concerning the roles of T-cell diversity in protective immunity and tolerance to healthy tissues and tumors.
Max ERC Funding
1 725 000 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym LeukemiaEnviron
Project SIGNALING PROPENSITY IN THE MICROENVIRONMENT OF B CELL CHRONIC LYMPHOCYTIC LEUKEMIA
Researcher (PI) Marek Mraz
Host Institution (HI) Masarykova univerzita
Call Details Starting Grant (StG), LS4, ERC-2018-STG
Summary B cell chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults. CLL cells are characterized by their universal dependency on pro-survival and pro-proliferative signals from immune niches. To achieve this they constantly re-circulate between blood and lymph nodes, which is inhibited by novel microenvironment-targeting therapies such as “BCR inhibitors”. We aim to reveal how the malignant B cells change the propensity of their signalling pathways in response to the different microenvironments such as peripheral blood vs lymph node to obtain the proliferative signals. This is of major relevance for CLL, but also transferable to the biology of some other B cell malignancies and/or normal B cells. We analyzed the “finger print” of microenvironmental interactions in many CLL samples at various times during the disease course or during therapy. The obtained data led us to hypothesize on the mechanisms of regulation of signalling propensity of two pathways that are responsible for proliferation and survival of CLL cells, namely B Cell Receptor (BCR) signalling and signals from T-cells mediated by CD40/IL4. In aim 1 we hypothesize that CD20 is one of the key proteins involved in CLL cell activation, and influences BCR and interleukin signalling (see figure). This has important therapeutic implication since CD20 is used as a therapeutic target for 20 years (rituximab), but its function in CLL/normal B cells is unknown. In aim 2 we hypothesize that miR-29 acts a key regulator of T-cell signalling from CD40 and down-stream NFkB activation (see figure). This represents the first example of miRNAs‘ role in the propensity of T-cell interaction, and could be also utilized therapeutically. In aim 3 we will integrate our data on microenvironmental signaling (aim 1+2) and develop a first mouse model for PDX that would allow stable engraftment of primary CLL cells. Currently, CLL is non-transplantable to any animal model which complicates studies of its biology.
Summary
B cell chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults. CLL cells are characterized by their universal dependency on pro-survival and pro-proliferative signals from immune niches. To achieve this they constantly re-circulate between blood and lymph nodes, which is inhibited by novel microenvironment-targeting therapies such as “BCR inhibitors”. We aim to reveal how the malignant B cells change the propensity of their signalling pathways in response to the different microenvironments such as peripheral blood vs lymph node to obtain the proliferative signals. This is of major relevance for CLL, but also transferable to the biology of some other B cell malignancies and/or normal B cells. We analyzed the “finger print” of microenvironmental interactions in many CLL samples at various times during the disease course or during therapy. The obtained data led us to hypothesize on the mechanisms of regulation of signalling propensity of two pathways that are responsible for proliferation and survival of CLL cells, namely B Cell Receptor (BCR) signalling and signals from T-cells mediated by CD40/IL4. In aim 1 we hypothesize that CD20 is one of the key proteins involved in CLL cell activation, and influences BCR and interleukin signalling (see figure). This has important therapeutic implication since CD20 is used as a therapeutic target for 20 years (rituximab), but its function in CLL/normal B cells is unknown. In aim 2 we hypothesize that miR-29 acts a key regulator of T-cell signalling from CD40 and down-stream NFkB activation (see figure). This represents the first example of miRNAs‘ role in the propensity of T-cell interaction, and could be also utilized therapeutically. In aim 3 we will integrate our data on microenvironmental signaling (aim 1+2) and develop a first mouse model for PDX that would allow stable engraftment of primary CLL cells. Currently, CLL is non-transplantable to any animal model which complicates studies of its biology.
Max ERC Funding
1 499 990 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym PIX
Project The Process Improvement Explorer: Automated Discovery and Assessment of Business Process Improvement Opportunities
Researcher (PI) Marlon DUMAS
Host Institution (HI) TARTU ULIKOOL
Call Details Advanced Grant (AdG), PE6, ERC-2018-ADG
Summary Business processes are the operational backbone of modern organizations. Their continuous improvement is key to the achievement of business objectives, be it with respect to efficiency, quality, compliance, or agility. Accordingly, a common task for process analysts is to discover and assess process improvement opportunities, i.e. changes to one or more processes, which are likely to improve them with respect to one or more performance measures. Current approaches to discover process improvement opportunities are expert-driven. In these approaches, data are used to assess opportunities derived from experience and intuition rather than to discover them in the first place. Moreover, as the assessment of opportunities is manual, analysts can only explore a fraction thereof.
PIX will build the foundations of a new generation of process improvement methods that do not exclusively rely on guidelines and heuristics, but rather on a systematic exploration of a space of possible changes derived from process execution data. Specifically, PIX will develop conceptual frameworks and algorithms to analyze process execution data in order to discover process changes corresponding to possible improvement opportunities, including changes in the control-flow dependencies between activities, partial automation of activities, changes in resource allocation rules, or changes in decision rules that may reduce wastes or negative outcomes. Each change will be associated with a multi-dimensional utility, thus allowing us to map a process improvement problem to an optimization problem over a multidimensional space. Given this mapping, PIX will develop efficient and incremental methods to search through said spaces in order to find Pareto-optimal groups of changes. The outputs will be embodied in a first-of-its-kind tool for automated process improvement discovery, which will lift the focus in the field of process mining from analyzing as-is processes to designing to-be processes.
Summary
Business processes are the operational backbone of modern organizations. Their continuous improvement is key to the achievement of business objectives, be it with respect to efficiency, quality, compliance, or agility. Accordingly, a common task for process analysts is to discover and assess process improvement opportunities, i.e. changes to one or more processes, which are likely to improve them with respect to one or more performance measures. Current approaches to discover process improvement opportunities are expert-driven. In these approaches, data are used to assess opportunities derived from experience and intuition rather than to discover them in the first place. Moreover, as the assessment of opportunities is manual, analysts can only explore a fraction thereof.
PIX will build the foundations of a new generation of process improvement methods that do not exclusively rely on guidelines and heuristics, but rather on a systematic exploration of a space of possible changes derived from process execution data. Specifically, PIX will develop conceptual frameworks and algorithms to analyze process execution data in order to discover process changes corresponding to possible improvement opportunities, including changes in the control-flow dependencies between activities, partial automation of activities, changes in resource allocation rules, or changes in decision rules that may reduce wastes or negative outcomes. Each change will be associated with a multi-dimensional utility, thus allowing us to map a process improvement problem to an optimization problem over a multidimensional space. Given this mapping, PIX will develop efficient and incremental methods to search through said spaces in order to find Pareto-optimal groups of changes. The outputs will be embodied in a first-of-its-kind tool for automated process improvement discovery, which will lift the focus in the field of process mining from analyzing as-is processes to designing to-be processes.
Max ERC Funding
2 349 965 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
