Project acronym ERA
Project Experimental Research into Ageing
Researcher (PI) Linda Partridge
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS4, ERC-2010-AdG_20100317
Summary The diseases of older age are a major challenge to human societies. Despite the complexity of ageing, both reduced food intake (dietary restriction) and simple genetic alterations can greatly increase lifespan and provide broad-spectrum protection against diseases of ageing in laboratory animals. Furthermore, there is strong evolutionary conservation of mechanisms. For instance the nutrient-sensing insulin/IGF and TOR signalling network modulates lifespan in yeast, invertebrates and rodents. There is thus a major scientific opportunity to use model organisms to discover how to ameliorate ageing and hence to protect against ageing-related disease in humans. Our recent findings on dietary amino acid balance in the fruit fly Drosophila imply that consumption of nutrients irrelevant to metabolism is life-shortening. Using a novel genomic approach, we shall determine if the same is true in mice and measure the role of dietary imbalance in extension of lifespan by dietary restriction. Late life dietary restriction in invertebrates can increase future survival as much as permanent restriction, implying that chemical mimetics administered late in life could also be fully effective. We shall determine if dietary restriction in mice has similarly acute effects, and use dietary switches to identify candidate mechanisms of increased health and lifespan. Recent evidence has pointed to particular components of nutrient-sensing pathways as promising drug targets for prevention of age-related disease, and we shall investigate two candidates. The work will break new ground in understanding how ageing is modulated by diet and signaling pathways and point to interventions that could protect against the effects of ageing to reduce the burden of ageing-related disease in humans.
Summary
The diseases of older age are a major challenge to human societies. Despite the complexity of ageing, both reduced food intake (dietary restriction) and simple genetic alterations can greatly increase lifespan and provide broad-spectrum protection against diseases of ageing in laboratory animals. Furthermore, there is strong evolutionary conservation of mechanisms. For instance the nutrient-sensing insulin/IGF and TOR signalling network modulates lifespan in yeast, invertebrates and rodents. There is thus a major scientific opportunity to use model organisms to discover how to ameliorate ageing and hence to protect against ageing-related disease in humans. Our recent findings on dietary amino acid balance in the fruit fly Drosophila imply that consumption of nutrients irrelevant to metabolism is life-shortening. Using a novel genomic approach, we shall determine if the same is true in mice and measure the role of dietary imbalance in extension of lifespan by dietary restriction. Late life dietary restriction in invertebrates can increase future survival as much as permanent restriction, implying that chemical mimetics administered late in life could also be fully effective. We shall determine if dietary restriction in mice has similarly acute effects, and use dietary switches to identify candidate mechanisms of increased health and lifespan. Recent evidence has pointed to particular components of nutrient-sensing pathways as promising drug targets for prevention of age-related disease, and we shall investigate two candidates. The work will break new ground in understanding how ageing is modulated by diet and signaling pathways and point to interventions that could protect against the effects of ageing to reduce the burden of ageing-related disease in humans.
Max ERC Funding
2 489 200 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym evolSingleCellGRN
Project Constraint, Adaptation, and Heterogeneity: Genomic and single-cell approaches to understanding the evolution of developmental gene regulatory networks
Researcher (PI) David GARFIELD
Host Institution (HI) HUMBOLDT-UNIVERSITAET ZU BERLIN
Call Details Starting Grant (StG), LS3, ERC-2018-STG
Summary Cell types in development arise from precise patterns of gene expression driven by differential usage of DNA regulatory elements. Mutations affecting these elements, or proteins binding them, are major contributors to disease and underlie the evolution of new morphologies. To better understand these elements and how they evolve, I introduce a set of single-cell RNA and ATAC-Seq sequencing technologies that: A) Identify tissue-specific regulatory elements and expression profiles by interrogating individual cells, B) Allow for a precise read-out of developmental responses to mutation and perturbation, including cell-fate re-specification, C) Lead to the development of a regulatory-information based concept of homology that will be used to understand developmental evolution. The research makes use of sea urchins. The well-annotated sea urchin regulatory network, a detailed understanding of inductive interactions in early development, and an active body of evolutionary research justify this choice. Using single-cell ATAC-Seq and a new method for resolving single-cell, nascent transcripts, I will build a detailed atlas of sea urchin development and use this atlas to understand how regulatory landscapes change during specification and how they evolve between closely related species. I will also investigate, at single-cell resolution, how larval skeletal cells are regenerated following the loss of a cell lineage that mirrors euechinoid evolution. To better understand the origins of cell types in sea urchins, I will characterize embryos of the cnidarian Nematostella, using shared regulatory sites to define cell types which I will compare to urchins and my previous work in Drosophila. The work will generate single-cell methods for non-traditional model systems and help to resolve the processes by which, and the paths along which, development evolves.
Summary
Cell types in development arise from precise patterns of gene expression driven by differential usage of DNA regulatory elements. Mutations affecting these elements, or proteins binding them, are major contributors to disease and underlie the evolution of new morphologies. To better understand these elements and how they evolve, I introduce a set of single-cell RNA and ATAC-Seq sequencing technologies that: A) Identify tissue-specific regulatory elements and expression profiles by interrogating individual cells, B) Allow for a precise read-out of developmental responses to mutation and perturbation, including cell-fate re-specification, C) Lead to the development of a regulatory-information based concept of homology that will be used to understand developmental evolution. The research makes use of sea urchins. The well-annotated sea urchin regulatory network, a detailed understanding of inductive interactions in early development, and an active body of evolutionary research justify this choice. Using single-cell ATAC-Seq and a new method for resolving single-cell, nascent transcripts, I will build a detailed atlas of sea urchin development and use this atlas to understand how regulatory landscapes change during specification and how they evolve between closely related species. I will also investigate, at single-cell resolution, how larval skeletal cells are regenerated following the loss of a cell lineage that mirrors euechinoid evolution. To better understand the origins of cell types in sea urchins, I will characterize embryos of the cnidarian Nematostella, using shared regulatory sites to define cell types which I will compare to urchins and my previous work in Drosophila. The work will generate single-cell methods for non-traditional model systems and help to resolve the processes by which, and the paths along which, development evolves.
Max ERC Funding
1 499 900 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym GENSTAGE
Project Genome Stability Mechanisms in Aging
Researcher (PI) Bjoern Schumacher
Host Institution (HI) KLINIKUM DER UNIVERSITAET ZU KOELN
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary Genome Instability has been recognized as causal factor of cancer and recently also as a major contributing factor of aging. A number of progeroid (premature aging-like) syndromes are linked to defects in nucleotide excision repair (NER). NER thus provides a highly relevant experimental system to study the role of genome stability in aging. Using the NER system we recently uncovered a novel link between DNA damage accumulation and the regulation of longevity assurance programs. We propose to use the powerful genetic system of C. elegans to identify mechanisms through which the stochastic accumulation of damage impacts aging and genetic pathways of longevity regulation. We will pursue three complementary experimental strategies: (1) genetic identification of novel response pathways to persistent DNA damage, (2) investigation of DNA damage resistance mechanisms that promote longevity, and (3) a targeted candidate approach to uncover the underlying mechanisms that ensure genome integrity in lifespan extension. This proposal aims at the discovery of novel genes functioning in genome stability and longevity regulation that might be instrumental for the development of preventive therapeutic strategies for age-related pathologies as well as for the treatment of rare genetic progeroid disorders.
Summary
Genome Instability has been recognized as causal factor of cancer and recently also as a major contributing factor of aging. A number of progeroid (premature aging-like) syndromes are linked to defects in nucleotide excision repair (NER). NER thus provides a highly relevant experimental system to study the role of genome stability in aging. Using the NER system we recently uncovered a novel link between DNA damage accumulation and the regulation of longevity assurance programs. We propose to use the powerful genetic system of C. elegans to identify mechanisms through which the stochastic accumulation of damage impacts aging and genetic pathways of longevity regulation. We will pursue three complementary experimental strategies: (1) genetic identification of novel response pathways to persistent DNA damage, (2) investigation of DNA damage resistance mechanisms that promote longevity, and (3) a targeted candidate approach to uncover the underlying mechanisms that ensure genome integrity in lifespan extension. This proposal aims at the discovery of novel genes functioning in genome stability and longevity regulation that might be instrumental for the development of preventive therapeutic strategies for age-related pathologies as well as for the treatment of rare genetic progeroid disorders.
Max ERC Funding
1 448 400 €
Duration
Start date: 2011-07-01, End date: 2017-02-28
Project acronym GREENLATPOL
Project Mechanisms underlying lateral polarity establishment in plant cells
Researcher (PI) Markus Grebe
Host Institution (HI) UNIVERSITAET POTSDAM
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary Higher plants and animals establish elaborate body plans with one end of the organism being different from another. Polar organisation is also of fundamental importance at the single-cell level, because mutations affecting cell polarity may cause severe body deformations. Hence, cell polarity is a central theme of biological research and much progress has been made towards our understanding of cellular polarisation along the shoot-root (apical-basal) axis of plants. By contrast, how polarity is established towards inner and outer lateral membranes of plant cells remains unresolved. Here, I propose to identify components controlling lateral cell polarity, employing the root epidermis of the genetic model plant Arabidopsis as an excellent system readily accessible for cell biological analyses. Root epidermal cells display polar nuclear movement towards the inner lateral membrane and proteins located at the outer lateral membrane. We will employ tools for visualization of these polar events that will enable us to A) perform forward genetic screens to discover signals and requirements for polar nuclear movement and outer lateral membrane polarity, B) apply forward and reverse genetics to unravel cytoskeletal requirements of lateral polarisation, C) employ live-cell imaging to reveal the dynamics of polarising events and D) combine genetic and cellular analyses with regulators of apical-basal polarity. Our work will uncover how a single cell separates and integrates polarising events along diverse axes. The proposed research is groundbreaking, as it will lay foundations for an understanding of lateral polarity establishment in plants. Finally, it will aid our understanding of how mechanisms underlying polarising events evolved differently in diverse multicellular organisms.
Summary
Higher plants and animals establish elaborate body plans with one end of the organism being different from another. Polar organisation is also of fundamental importance at the single-cell level, because mutations affecting cell polarity may cause severe body deformations. Hence, cell polarity is a central theme of biological research and much progress has been made towards our understanding of cellular polarisation along the shoot-root (apical-basal) axis of plants. By contrast, how polarity is established towards inner and outer lateral membranes of plant cells remains unresolved. Here, I propose to identify components controlling lateral cell polarity, employing the root epidermis of the genetic model plant Arabidopsis as an excellent system readily accessible for cell biological analyses. Root epidermal cells display polar nuclear movement towards the inner lateral membrane and proteins located at the outer lateral membrane. We will employ tools for visualization of these polar events that will enable us to A) perform forward genetic screens to discover signals and requirements for polar nuclear movement and outer lateral membrane polarity, B) apply forward and reverse genetics to unravel cytoskeletal requirements of lateral polarisation, C) employ live-cell imaging to reveal the dynamics of polarising events and D) combine genetic and cellular analyses with regulators of apical-basal polarity. Our work will uncover how a single cell separates and integrates polarising events along diverse axes. The proposed research is groundbreaking, as it will lay foundations for an understanding of lateral polarity establishment in plants. Finally, it will aid our understanding of how mechanisms underlying polarising events evolved differently in diverse multicellular organisms.
Max ERC Funding
1 363 452 €
Duration
Start date: 2010-12-01, End date: 2016-11-30
Project acronym HIGHWIND
Project Simulation, Optimization and Control of High-Altitude
Wind Power Generators
Researcher (PI) Moritz Mathias Diehl
Host Institution (HI) ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
Call Details Starting Grant (StG), PE7, ERC-2010-StG_20091028
Summary A new class of large scale wind power generators shall be investigated via
mathematical modelling, computer simulation and multidisciplinary optimization methods. The underlying
technical idea is to use fast flying tethered airfoils that fly in altitudes of several hundred
meters above the ground. They will perform specially controlled loops accompanied by line length
and line tension variations, that are used to drive a generator on the ground.
Being a high risk / high gain technology, the applicant believes that the main focus in the first development
years should not be on building large and expensive experimental setups (as some courageous
experimentalists currently do in Europe and the US), but on mathematical modelling, computer
simulation and optimization studies, accompanied by only small scale experiments for model
and control system validation. This will help finding optimal system designs before expensive and
potentially dangerous large scale systems are built. The research requires an interdisciplinary collaboration
of scientists from mathematical, mechanical, aerospace, and control engineering, as well
as from the computational sciences. At the end of the project, a small scale, automatically flying prototype shall be realized, accompanied
by validated and scalable mathematical models and a toolbox of efficient computational methods
for simulation and multidisciplinary optimization of high altitude wind power systems. If successful,
the project will help to establish this new type of wind power generator that might provide electricity
more cheaply than fossil fuels and is deployable at considerably more sites than conventional windmills.
Summary
A new class of large scale wind power generators shall be investigated via
mathematical modelling, computer simulation and multidisciplinary optimization methods. The underlying
technical idea is to use fast flying tethered airfoils that fly in altitudes of several hundred
meters above the ground. They will perform specially controlled loops accompanied by line length
and line tension variations, that are used to drive a generator on the ground.
Being a high risk / high gain technology, the applicant believes that the main focus in the first development
years should not be on building large and expensive experimental setups (as some courageous
experimentalists currently do in Europe and the US), but on mathematical modelling, computer
simulation and optimization studies, accompanied by only small scale experiments for model
and control system validation. This will help finding optimal system designs before expensive and
potentially dangerous large scale systems are built. The research requires an interdisciplinary collaboration
of scientists from mathematical, mechanical, aerospace, and control engineering, as well
as from the computational sciences. At the end of the project, a small scale, automatically flying prototype shall be realized, accompanied
by validated and scalable mathematical models and a toolbox of efficient computational methods
for simulation and multidisciplinary optimization of high altitude wind power systems. If successful,
the project will help to establish this new type of wind power generator that might provide electricity
more cheaply than fossil fuels and is deployable at considerably more sites than conventional windmills.
Max ERC Funding
1 499 800 €
Duration
Start date: 2011-03-01, End date: 2017-02-28
Project acronym IMMUNOTHROMBOSIS
Project Cross-talk between platelets and immunity - implications for host homeostasis and defense
Researcher (PI) Steffen MASSBERG
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS4, ERC-2018-ADG
Summary The overall aim of the IMMUNOTHROMBOSIS project is to clarify the mechanisms underlying the recently identified synergism between thrombosis and inflammation. Thrombus formation and inflammation are vital host responses that ensure homeostasis, but can also drive cardiovascular disease, including myocardial infarction and stroke, the major causes of death in Europe. My group and others discovered, that thrombosis and inflammation are not to be considered separate processes. They are tightly interrelated and synergize in immune defence, but also in inflammatory and thrombotic diseases in a process we termed immunothrombosis. Targeting this synergism has great potential to identify innovative and unconventional strategies to more specifically prevent undesired activation of thrombotic and inflammatory pathways. However, this requires a deeper mechanistic understanding of immunothrombosis. I recently identified two ground-breaking novel immunothrombotic principles: I discovered that platelets have the ability to migrate autonomously, which assists immune cells in fighting pathogens. Further, I revealed that immune cells play a central role in controlling the production of platelets from their megakaryocyte precursors. The physiological and pathophysiological relevance of both processes is unclear. This is the starting point and focus of the IMMUNOTHROMBOSIS project. My aim is to define how platelets use their ability to migrate to support immune cells in protection of vascular integrity (objective 1) and to identify the contribution of platelet migration to different cardiovascular diseases involving immunothrombotic tissue damage (objective 2). Finally, I will clarify how inflammatory responses feedback to the production of thrombotic effectors and dissect inflammatory mechanisms that control platelet production (objective 3). IMMUNOTHROMBOSIS will identify new options for specific prevention or treatment of thrombotic and inflammatory cardiovascular diseases.
Summary
The overall aim of the IMMUNOTHROMBOSIS project is to clarify the mechanisms underlying the recently identified synergism between thrombosis and inflammation. Thrombus formation and inflammation are vital host responses that ensure homeostasis, but can also drive cardiovascular disease, including myocardial infarction and stroke, the major causes of death in Europe. My group and others discovered, that thrombosis and inflammation are not to be considered separate processes. They are tightly interrelated and synergize in immune defence, but also in inflammatory and thrombotic diseases in a process we termed immunothrombosis. Targeting this synergism has great potential to identify innovative and unconventional strategies to more specifically prevent undesired activation of thrombotic and inflammatory pathways. However, this requires a deeper mechanistic understanding of immunothrombosis. I recently identified two ground-breaking novel immunothrombotic principles: I discovered that platelets have the ability to migrate autonomously, which assists immune cells in fighting pathogens. Further, I revealed that immune cells play a central role in controlling the production of platelets from their megakaryocyte precursors. The physiological and pathophysiological relevance of both processes is unclear. This is the starting point and focus of the IMMUNOTHROMBOSIS project. My aim is to define how platelets use their ability to migrate to support immune cells in protection of vascular integrity (objective 1) and to identify the contribution of platelet migration to different cardiovascular diseases involving immunothrombotic tissue damage (objective 2). Finally, I will clarify how inflammatory responses feedback to the production of thrombotic effectors and dissect inflammatory mechanisms that control platelet production (objective 3). IMMUNOTHROMBOSIS will identify new options for specific prevention or treatment of thrombotic and inflammatory cardiovascular diseases.
Max ERC Funding
2 321 416 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym inCREASE
Project Coding for Security and DNA Storage
Researcher (PI) Antonia Wachter-Zeh
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), PE7, ERC-2018-STG
Summary Communication and data storage systems are indispensable parts of our every-day life. However, these systems deal with severe challenges in security and reliability. Security is important whenever a user communicates or stores sensitive data, e.g., medical information; reliability has to be guaranteed to be able to transmit or store information while noise occurs. Algebraic codes (ACs) are a powerful means to achieve both.
Within inCREASE, I will construct and evaluate special codes for security applications and DNA storage.
The tasks are structured into three work packages: (1) post-quantum secure code-based cryptosystems, (2) secure key regeneration based on ACs, (3) ACs for DNA-based storage systems. The focus of inCREASE
lies on innovative theoretical concepts.
The goal of work package (1) is to investigate and design code-based cryptosystems; one promising idea is to apply insertion/deletion correcting codes. The security of these systems will be analysed from two points of view: structural attacks on the algorithms and hardware implementations with side-channel attacks.
Secure cryptographic key regeneration is the goal of (2) and can be achieved by physical unclonable functions (PUFs). Here, ACs are necessary to reproduce the key reliably. This project will study the error patterns that occur in PUFs, model them theoretically, and design suitable coding schemes.
The investigation on (3) will start with a study of the data of existing DNA storage systems. The outcome will be an error model that will include insertions, deletions, substitutions, and duplications. Therefore, inCREASE will design ACs for these error types. This will be especially challenging regarding the mathematical concepts. These codes will be evaluated by simulations and using data sets of DNA storage systems.
This project is high risk/high gain with impact not only to storage and security, but to the methodology as well as other areas such as communications.
Summary
Communication and data storage systems are indispensable parts of our every-day life. However, these systems deal with severe challenges in security and reliability. Security is important whenever a user communicates or stores sensitive data, e.g., medical information; reliability has to be guaranteed to be able to transmit or store information while noise occurs. Algebraic codes (ACs) are a powerful means to achieve both.
Within inCREASE, I will construct and evaluate special codes for security applications and DNA storage.
The tasks are structured into three work packages: (1) post-quantum secure code-based cryptosystems, (2) secure key regeneration based on ACs, (3) ACs for DNA-based storage systems. The focus of inCREASE
lies on innovative theoretical concepts.
The goal of work package (1) is to investigate and design code-based cryptosystems; one promising idea is to apply insertion/deletion correcting codes. The security of these systems will be analysed from two points of view: structural attacks on the algorithms and hardware implementations with side-channel attacks.
Secure cryptographic key regeneration is the goal of (2) and can be achieved by physical unclonable functions (PUFs). Here, ACs are necessary to reproduce the key reliably. This project will study the error patterns that occur in PUFs, model them theoretically, and design suitable coding schemes.
The investigation on (3) will start with a study of the data of existing DNA storage systems. The outcome will be an error model that will include insertions, deletions, substitutions, and duplications. Therefore, inCREASE will design ACs for these error types. This will be especially challenging regarding the mathematical concepts. These codes will be evaluated by simulations and using data sets of DNA storage systems.
This project is high risk/high gain with impact not only to storage and security, but to the methodology as well as other areas such as communications.
Max ERC Funding
1 471 750 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym IntegraBrain
Project Integrated Implant Technology for Multi-modal Brain Interfaces
Researcher (PI) Ivan MINEV
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Call Details Starting Grant (StG), PE7, ERC-2018-STG
Summary Bioelectronic medicine may soon replace systemic drugs for treating some chronic conditions. The clinician will implant a miniature laboratory to deliver and coordinate a multi-modal treatment program directly at the affected tissue. The technology to bring this vision to the clinic is not yet available.
The IntegraBrain project will contribute by building an implantable network of sensors and actuators. Actuators will deploy electricity, light, drugs and thermal energy as modalities of the therapeutic program, while sensors will monitor its progress. A key technological advance will be a method for direct writing of the sensor-actuator network. To achieve this, we will develop a palette of functional inks where each ink supports one of the therapeutic modalities.
The technology has the potential to be tailored for applications in soft tissue organs, especially in the nervous system, where injury or degeneration can result in chronic disability. We will apply IntegraBrain technology in two niches of the nervous system in rodents. In the central nervous system, we will demonstrate seizure control by multi-modal neuromodulation. In the peripheral nervous system, we will demonstrate reversible block and excitation. For the first time, we will observe if multi-modal neuromodulation leads to synergistic effects on the nervous system.
With the IntegraBrain project, we hope to catalyse pre-clinical development of implantable human-machine interfaces for therapeutic applications.
Summary
Bioelectronic medicine may soon replace systemic drugs for treating some chronic conditions. The clinician will implant a miniature laboratory to deliver and coordinate a multi-modal treatment program directly at the affected tissue. The technology to bring this vision to the clinic is not yet available.
The IntegraBrain project will contribute by building an implantable network of sensors and actuators. Actuators will deploy electricity, light, drugs and thermal energy as modalities of the therapeutic program, while sensors will monitor its progress. A key technological advance will be a method for direct writing of the sensor-actuator network. To achieve this, we will develop a palette of functional inks where each ink supports one of the therapeutic modalities.
The technology has the potential to be tailored for applications in soft tissue organs, especially in the nervous system, where injury or degeneration can result in chronic disability. We will apply IntegraBrain technology in two niches of the nervous system in rodents. In the central nervous system, we will demonstrate seizure control by multi-modal neuromodulation. In the peripheral nervous system, we will demonstrate reversible block and excitation. For the first time, we will observe if multi-modal neuromodulation leads to synergistic effects on the nervous system.
With the IntegraBrain project, we hope to catalyse pre-clinical development of implantable human-machine interfaces for therapeutic applications.
Max ERC Funding
1 496 000 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ISLETVASC
Project Molecular Mechanisms Regulating Pancreatic Islet Vascularization
Researcher (PI) Matthew Poy
Host Institution (HI) MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC)
Call Details Starting Grant (StG), LS4, ERC-2010-StG_20091118
Summary Many reports indicate the number of people with diabetes will exceed 350 million by the year 2030. Both type 1 and type 2 diabetes are characterized by the deterioration and impaired function of pancreatic b-cells. While transplantation is a promising strategy to replace lost tissue, several obstacles remain in the pathway to its clinical application. Whether b-cells are derived from patient samples or differentiated from embryonic stem cells, a major concern facing these strategies is how a recipient will respond to transplanted foreign tissue. Since the native environment for pancreatic islets is comprised of neural and vascular networks, successful integration may depend upon signals received from these neighboring cell types. Using a multidisciplinary approach, the principal investigator plans to elucidate molecular mechanisms underlying the interactions between pancreatic islet cells and their neighboring endothelial cells. Developing an understanding of how these interactions change during the pathogenesis of disease will provide insight into how islet growth and insulin release is dependent upon signals received from adjacent cell types. Emphasis will be placed on genetic mouse models to measure changes in gene expression in both isolated pancreatic b-cells and endothelial cells to identify genes that mediate the interaction between these cell types. In addition, it is of great interest to identify secreted factors that may constitute autocrine or paracrine signalling mechanisms that influence growth and function between these cell types. Furthermore, it will be determined whether current protocols for the differentiation of mouse stem cells into insulin producing cells are improved by restoring the expression of genes which facilitate communication to endothelial cells. This project aims to identify genes essential to the vascular context of pancreatic b-cells to improve transplantation protocols and facilitate the development of therapeutic strategies for diabetes.
Summary
Many reports indicate the number of people with diabetes will exceed 350 million by the year 2030. Both type 1 and type 2 diabetes are characterized by the deterioration and impaired function of pancreatic b-cells. While transplantation is a promising strategy to replace lost tissue, several obstacles remain in the pathway to its clinical application. Whether b-cells are derived from patient samples or differentiated from embryonic stem cells, a major concern facing these strategies is how a recipient will respond to transplanted foreign tissue. Since the native environment for pancreatic islets is comprised of neural and vascular networks, successful integration may depend upon signals received from these neighboring cell types. Using a multidisciplinary approach, the principal investigator plans to elucidate molecular mechanisms underlying the interactions between pancreatic islet cells and their neighboring endothelial cells. Developing an understanding of how these interactions change during the pathogenesis of disease will provide insight into how islet growth and insulin release is dependent upon signals received from adjacent cell types. Emphasis will be placed on genetic mouse models to measure changes in gene expression in both isolated pancreatic b-cells and endothelial cells to identify genes that mediate the interaction between these cell types. In addition, it is of great interest to identify secreted factors that may constitute autocrine or paracrine signalling mechanisms that influence growth and function between these cell types. Furthermore, it will be determined whether current protocols for the differentiation of mouse stem cells into insulin producing cells are improved by restoring the expression of genes which facilitate communication to endothelial cells. This project aims to identify genes essential to the vascular context of pancreatic b-cells to improve transplantation protocols and facilitate the development of therapeutic strategies for diabetes.
Max ERC Funding
1 496 257 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym justITSELF
Project Just-in-time Self-Verification of Autonomous Systems
Researcher (PI) Matthias ALTHOFF
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Call Details Consolidator Grant (CoG), PE7, ERC-2018-COG
Summary Engineers and computer scientists are currently developing autonomous systems whose entire set of behaviors in future, untested situations is unknown: How can a designer foresee all situations that an autonomous road vehicle, a robot in a human environment, an agricultural robot, or an unmanned aerial vehicle will face? Keeping in mind that all these examples are safety-critical, it is irresponsible to deploy such systems without testing all possible situations---this, however, seems impossible since even the most important possible situations are unmanageably many. I propose a paradigm shift that will make it possible to guarantee safety in unforeseeable situations: Instead of verifying the correctness of a system before deployment, I propose just-in-time verification, a new, to-be-developed verification paradigm where a system continuously checks the correctness of its next action by itself in its current environment (and only in it) in a just-in-time manner. Since future autonomous systems will have a tight interconnection of discrete computing and continuous physical elements, also known as cyber-physical systems, I will develop just-in-time verification for this system class. In order to prove correct behavior of cyber-physical systems, I will develop new formal verification techniques that efficiently compute possible future behaviors---subject to uncertain initial states, inputs, and parameters---within a small time horizon. Just-in-time verification will substantially cut development costs, increase the autonomy of systems (e.g., the range of deployment of automated driving systems), and reduce or even eliminate certain liability claims. The results will be implemented in an open-source software framework and will be primarily demonstrated for automated driving. Successful development of just-in-time verification techniques is yet more challenging than offline verification of autonomous systems, but expected to bring even greater rewards.
Summary
Engineers and computer scientists are currently developing autonomous systems whose entire set of behaviors in future, untested situations is unknown: How can a designer foresee all situations that an autonomous road vehicle, a robot in a human environment, an agricultural robot, or an unmanned aerial vehicle will face? Keeping in mind that all these examples are safety-critical, it is irresponsible to deploy such systems without testing all possible situations---this, however, seems impossible since even the most important possible situations are unmanageably many. I propose a paradigm shift that will make it possible to guarantee safety in unforeseeable situations: Instead of verifying the correctness of a system before deployment, I propose just-in-time verification, a new, to-be-developed verification paradigm where a system continuously checks the correctness of its next action by itself in its current environment (and only in it) in a just-in-time manner. Since future autonomous systems will have a tight interconnection of discrete computing and continuous physical elements, also known as cyber-physical systems, I will develop just-in-time verification for this system class. In order to prove correct behavior of cyber-physical systems, I will develop new formal verification techniques that efficiently compute possible future behaviors---subject to uncertain initial states, inputs, and parameters---within a small time horizon. Just-in-time verification will substantially cut development costs, increase the autonomy of systems (e.g., the range of deployment of automated driving systems), and reduce or even eliminate certain liability claims. The results will be implemented in an open-source software framework and will be primarily demonstrated for automated driving. Successful development of just-in-time verification techniques is yet more challenging than offline verification of autonomous systems, but expected to bring even greater rewards.
Max ERC Funding
1 999 075 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
