Project acronym ANIMETRICS
Project Measurement-Based Modeling and Animation of Complex Mechanical Phenomena
Researcher (PI) Miguel Angel Otaduy Tristan
Host Institution (HI) UNIVERSIDAD REY JUAN CARLOS
Call Details Starting Grant (StG), PE6, ERC-2011-StG_20101014
Summary Computer animation has traditionally been associated with applications in virtual-reality-based training, video games or feature films. However, interactive animation is gaining relevance in a more general scope, as a tool for early-stage analysis, design and planning in many applications in science and engineering. The user can get quick and visual feedback of the results, and then proceed by refining the experiments or designs. Potential applications include nanodesign, e-commerce or tactile telecommunication, but they also reach as far as, e.g., the analysis of ecological, climate, biological or physiological processes.
The application of computer animation is extremely limited in comparison to its potential outreach due to a trade-off between accuracy and computational efficiency. Such trade-off is induced by inherent complexity sources such as nonlinear or anisotropic behaviors, heterogeneous properties, or high dynamic ranges of effects.
The Animetrics project proposes a modeling and animation methodology, which consists of a multi-scale decomposition of complex processes, the description of the process at each scale through combination of simple local models, and fitting the parameters of those local models using large amounts of data from example effects. The modeling and animation methodology will be explored on specific problems arising in complex mechanical phenomena, including viscoelasticity of solids and thin shells, multi-body contact, granular and liquid flow, and fracture of solids.
Summary
Computer animation has traditionally been associated with applications in virtual-reality-based training, video games or feature films. However, interactive animation is gaining relevance in a more general scope, as a tool for early-stage analysis, design and planning in many applications in science and engineering. The user can get quick and visual feedback of the results, and then proceed by refining the experiments or designs. Potential applications include nanodesign, e-commerce or tactile telecommunication, but they also reach as far as, e.g., the analysis of ecological, climate, biological or physiological processes.
The application of computer animation is extremely limited in comparison to its potential outreach due to a trade-off between accuracy and computational efficiency. Such trade-off is induced by inherent complexity sources such as nonlinear or anisotropic behaviors, heterogeneous properties, or high dynamic ranges of effects.
The Animetrics project proposes a modeling and animation methodology, which consists of a multi-scale decomposition of complex processes, the description of the process at each scale through combination of simple local models, and fitting the parameters of those local models using large amounts of data from example effects. The modeling and animation methodology will be explored on specific problems arising in complex mechanical phenomena, including viscoelasticity of solids and thin shells, multi-body contact, granular and liquid flow, and fracture of solids.
Max ERC Funding
1 277 969 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym ANTICS
Project Algorithmic Number Theory in Computer Science
Researcher (PI) Andreas Enge
Host Institution (HI) INSTITUT NATIONAL DE RECHERCHE ENINFORMATIQUE ET AUTOMATIQUE
Call Details Starting Grant (StG), PE6, ERC-2011-StG_20101014
Summary "During the past twenty years, we have witnessed profound technological changes, summarised under the terms of digital revolution or entering the information age. It is evident that these technological changes will have a deep societal impact, and questions of privacy and security are primordial to ensure the survival of a free and open society.
Cryptology is a main building block of any security solution, and at the heart of projects such as electronic identity and health cards, access control, digital content distribution or electronic voting, to mention only a few important applications. During the past decades, public-key cryptology has established itself as a research topic in computer science; tools of theoretical computer science are employed to “prove” the security of cryptographic primitives such as encryption or digital signatures and of more complex protocols. It is often forgotten, however, that all practically relevant public-key cryptosystems are rooted in pure mathematics, in particular, number theory and arithmetic geometry. In fact, the socalled security “proofs” are all conditional to the algorithmic untractability of certain number theoretic problems, such as factorisation of large integers or discrete logarithms in algebraic curves. Unfortunately, there is a large cultural gap between computer scientists using a black-box security reduction to a supposedly hard problem in algorithmic number theory and number theorists, who are often interested in solving small and easy instances of the same problem. The theoretical grounds on which current algorithmic number theory operates are actually rather shaky, and cryptologists are generally unaware of this fact.
The central goal of ANTICS is to rebuild algorithmic number theory on the firm grounds of theoretical computer science."
Summary
"During the past twenty years, we have witnessed profound technological changes, summarised under the terms of digital revolution or entering the information age. It is evident that these technological changes will have a deep societal impact, and questions of privacy and security are primordial to ensure the survival of a free and open society.
Cryptology is a main building block of any security solution, and at the heart of projects such as electronic identity and health cards, access control, digital content distribution or electronic voting, to mention only a few important applications. During the past decades, public-key cryptology has established itself as a research topic in computer science; tools of theoretical computer science are employed to “prove” the security of cryptographic primitives such as encryption or digital signatures and of more complex protocols. It is often forgotten, however, that all practically relevant public-key cryptosystems are rooted in pure mathematics, in particular, number theory and arithmetic geometry. In fact, the socalled security “proofs” are all conditional to the algorithmic untractability of certain number theoretic problems, such as factorisation of large integers or discrete logarithms in algebraic curves. Unfortunately, there is a large cultural gap between computer scientists using a black-box security reduction to a supposedly hard problem in algorithmic number theory and number theorists, who are often interested in solving small and easy instances of the same problem. The theoretical grounds on which current algorithmic number theory operates are actually rather shaky, and cryptologists are generally unaware of this fact.
The central goal of ANTICS is to rebuild algorithmic number theory on the firm grounds of theoretical computer science."
Max ERC Funding
1 453 507 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym DYNACOM
Project From Genome Integrity to Genome Plasticity:
Dynamic Complexes Controlling Once per Cell Cycle Replication
Researcher (PI) Zoi Lygerou
Host Institution (HI) PANEPISTIMIO PATRON
Call Details Starting Grant (StG), LS3, ERC-2011-StG_20101109
Summary Accurate genome duplication is controlled by multi-subunit protein complexes which associate with chromatin and dictate when and where replication should take place. Dynamic changes in these complexes lie at the heart of their ability to ensure the maintenance of genomic integrity. Defects in origin bound complexes lead to re-replication of the genome across evolution, have been linked to DNA-replication stress and may predispose for gene amplification events. Such genomic aberrations are central to malignant transformation.
We wish to understand how once per cell cycle replication is normally controlled within the context of the living cell and how defects in this control may result in loss of genome integrity and provide genome plasticity. To this end, live cell imaging in human cells in culture will be combined with genetic studies in fission yeast and modelling and in silico analysis.
The proposed research aims to:
1. Decipher the regulatory mechanisms which act in time and space to ensure once per cell cycle replication within living cells and how they may be affected by system aberrations, using functional live cell imaging.
2. Test whether aberrations in the licensing system may provide a selective advantage, through amplification of multiple genomic loci. To this end, a natural selection experiment will be set up in fission yeast .
3. Investigate how rereplication takes place along the genome in single cells. Is there heterogeneity amongst a population, leading to a plethora of different genotypes? In silico analysis of full genome DNA rereplication will be combined to single cell analysis in fission yeast.
4. Assess the relevance of our findings for gene amplification events in cancer. Does ectopic expression of human Cdt1/Cdc6 in cancer cells enhance drug resistance through gene amplification?
Our findings are expected to offer novel insight into mechanisms underlying cancer development and progression.
Summary
Accurate genome duplication is controlled by multi-subunit protein complexes which associate with chromatin and dictate when and where replication should take place. Dynamic changes in these complexes lie at the heart of their ability to ensure the maintenance of genomic integrity. Defects in origin bound complexes lead to re-replication of the genome across evolution, have been linked to DNA-replication stress and may predispose for gene amplification events. Such genomic aberrations are central to malignant transformation.
We wish to understand how once per cell cycle replication is normally controlled within the context of the living cell and how defects in this control may result in loss of genome integrity and provide genome plasticity. To this end, live cell imaging in human cells in culture will be combined with genetic studies in fission yeast and modelling and in silico analysis.
The proposed research aims to:
1. Decipher the regulatory mechanisms which act in time and space to ensure once per cell cycle replication within living cells and how they may be affected by system aberrations, using functional live cell imaging.
2. Test whether aberrations in the licensing system may provide a selective advantage, through amplification of multiple genomic loci. To this end, a natural selection experiment will be set up in fission yeast .
3. Investigate how rereplication takes place along the genome in single cells. Is there heterogeneity amongst a population, leading to a plethora of different genotypes? In silico analysis of full genome DNA rereplication will be combined to single cell analysis in fission yeast.
4. Assess the relevance of our findings for gene amplification events in cancer. Does ectopic expression of human Cdt1/Cdc6 in cancer cells enhance drug resistance through gene amplification?
Our findings are expected to offer novel insight into mechanisms underlying cancer development and progression.
Max ERC Funding
1 531 000 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym EXPRESSIVE
Project EXPloring REsponsive Shapes for Seamless desIgn of Virtual Environments
be retained
Researcher (PI) Marie-Paule Renée Cani
Host Institution (HI) INSTITUT POLYTECHNIQUE DE GRENOBLE
Call Details Advanced Grant (AdG), PE6, ERC-2011-ADG_20110209
Summary Despite our great expressive skills, we humans lack an easy way of communicating the 3D shapes we imagine, and even more so when it comes to dynamic shapes. Over centuries humans used drawing and sculpture to convey shapes. These tools require significant expertise and time investment, especially if one aims to describe complex or dynamic shapes. With the advent of virtual environments one would expect digital modeling to replace these traditional tools. Unfortunately, conventional techniques in the area have failed, since even trained computer artists still create with traditional media and only use the computer to reproduce already designed content.
Could digital media be turned into a tool, even more expressive and simpler to use than a pen, to convey and refine both static and dynamic 3D shapes? This is the goal of this project. Achieving it will make shape design directly possible in virtual form, from early drafting to progressive refinement and finalization of an idea. To this end, models for shape and motion need to be totally rethought from a user-centered perspective . Specifically, we propose the new paradigm of responsive 3D shapes – a novel representation separating morphology from isometric embedding – to define high-level, dynamic 3D content that takes form, is refined, moves and deforms based on user intent, expressed through intuitive interaction gestures.
Scientifically, while the problem we address belongs to Computer Graphics, it calls for a new convergence with Geometry, Simulation and Human Computer Interaction. In terms of impact, the resulting “expressive virtual pen” for 3D content will not only serve the needs of artists, but also of scientists and engineers willing to refine their thoughts by interacting with prototypes of their objects of study, educators and media aiming at quickly conveying their ideas, as well as anyone willing to communicate a 3D shape This project thus opens up new horizons for science, technology and society.
Summary
Despite our great expressive skills, we humans lack an easy way of communicating the 3D shapes we imagine, and even more so when it comes to dynamic shapes. Over centuries humans used drawing and sculpture to convey shapes. These tools require significant expertise and time investment, especially if one aims to describe complex or dynamic shapes. With the advent of virtual environments one would expect digital modeling to replace these traditional tools. Unfortunately, conventional techniques in the area have failed, since even trained computer artists still create with traditional media and only use the computer to reproduce already designed content.
Could digital media be turned into a tool, even more expressive and simpler to use than a pen, to convey and refine both static and dynamic 3D shapes? This is the goal of this project. Achieving it will make shape design directly possible in virtual form, from early drafting to progressive refinement and finalization of an idea. To this end, models for shape and motion need to be totally rethought from a user-centered perspective . Specifically, we propose the new paradigm of responsive 3D shapes – a novel representation separating morphology from isometric embedding – to define high-level, dynamic 3D content that takes form, is refined, moves and deforms based on user intent, expressed through intuitive interaction gestures.
Scientifically, while the problem we address belongs to Computer Graphics, it calls for a new convergence with Geometry, Simulation and Human Computer Interaction. In terms of impact, the resulting “expressive virtual pen” for 3D content will not only serve the needs of artists, but also of scientists and engineers willing to refine their thoughts by interacting with prototypes of their objects of study, educators and media aiming at quickly conveying their ideas, as well as anyone willing to communicate a 3D shape This project thus opens up new horizons for science, technology and society.
Max ERC Funding
2 498 116 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym FliesCan
Project Modelling Cancer Traits in Drosophila
Researcher (PI) Cayetano Gonzalez Hernandez
Host Institution (HI) FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Call Details Advanced Grant (AdG), LS3, ERC-2011-ADG_20110310
Summary Despite significant advance, cancer treatment remains suboptimal. Anatomical and physiological differences between humans and simple model organisms like Drosophila are many and major, and preclude the modelling of key aspects of the disease as it proceeds in vertebrates. However, malignant tumors in vertebrates and flies are made of cells that have derailed from their normal course of development, grow out of control, become immortal, invasive, and kill the host. Moreover, like most solid human tumors, Drosophila malignant tumors display chromosomal instability and copy number variation. In addition, some of them are characterized by the upregulation of germline genes, a distinct feature of certain human cancers. Drosophila tumor models offer an unprecedented opportunity to study these basic malignant traits, which characterize human tumors, in a genetically tractable organism, applying sophisticated genome-wide and comprehensive functional assays at a rate and with a level of detail that are not possible in vertebrates. The goal of this project is twofold: (1) to identify new paths of intervention to inhibit tumor growth, and (2) to determine the origin and function of aneuploidy and changes in gene copy number in malignant growth. We are expectant that the results obtained during the course of this project might eventually have a real impact in human health.
Summary
Despite significant advance, cancer treatment remains suboptimal. Anatomical and physiological differences between humans and simple model organisms like Drosophila are many and major, and preclude the modelling of key aspects of the disease as it proceeds in vertebrates. However, malignant tumors in vertebrates and flies are made of cells that have derailed from their normal course of development, grow out of control, become immortal, invasive, and kill the host. Moreover, like most solid human tumors, Drosophila malignant tumors display chromosomal instability and copy number variation. In addition, some of them are characterized by the upregulation of germline genes, a distinct feature of certain human cancers. Drosophila tumor models offer an unprecedented opportunity to study these basic malignant traits, which characterize human tumors, in a genetically tractable organism, applying sophisticated genome-wide and comprehensive functional assays at a rate and with a level of detail that are not possible in vertebrates. The goal of this project is twofold: (1) to identify new paths of intervention to inhibit tumor growth, and (2) to determine the origin and function of aneuploidy and changes in gene copy number in malignant growth. We are expectant that the results obtained during the course of this project might eventually have a real impact in human health.
Max ERC Funding
2 406 000 €
Duration
Start date: 2012-07-01, End date: 2017-06-30
Project acronym FlowMachines
Project Flow Machines: Interacting with Style
Researcher (PI) Francois Pachet
Host Institution (HI) UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6
Call Details Advanced Grant (AdG), PE6, ERC-2011-ADG_20110209
Summary Content creation is a fundamental activity for developing identities in modern individuals. Yet creativity is hardly addressed by computer science. This project addresses the issue of content creation from the perspective of Flow machines. Flow machines are interactive systems that learn how to generate content, text or music, in the user’s style. Thanks to controlled generation mechanisms, the user can then steer the machine to generate content that fits with their intentions. Flow interactions induce a multiplicative effect that boosts creativity and prompts the user to reflect on their own style. This vision stems from the success stories of several computer-assisted musical systems that showed how interactive dialogs with self-learning interactions provoke flow states.
To enables full control of stylistic generation, the scientific challenge is the reification of style as a flexible texture. This challenge will be addressed by pursuing three original directions in the fields of statistical learning and combinatorial optimization: 1) the formulation of Markov-based generation as a constraint problem, 2) the development of feature generation techniques for feeding machine learning algorithms and 3) the development of techniques to transform descriptors into controllers.
Two large-scale studies will be conducted with well-known creators using these Flow machines, during which the whole creation process will be recorded, stored, and analyzed, providing the first complete chronicles of professional-level artifacts. The artifacts, a music album and a novel, will be published in their respective ecosystems, and the reaction of the audience will be measured and analyzed to further assess the impact of Flow machines on creation. The technologies developed and the pilot studies will serve as pioneering experiments to turn Flow machines into a field of study and explore other domains of creation.
Summary
Content creation is a fundamental activity for developing identities in modern individuals. Yet creativity is hardly addressed by computer science. This project addresses the issue of content creation from the perspective of Flow machines. Flow machines are interactive systems that learn how to generate content, text or music, in the user’s style. Thanks to controlled generation mechanisms, the user can then steer the machine to generate content that fits with their intentions. Flow interactions induce a multiplicative effect that boosts creativity and prompts the user to reflect on their own style. This vision stems from the success stories of several computer-assisted musical systems that showed how interactive dialogs with self-learning interactions provoke flow states.
To enables full control of stylistic generation, the scientific challenge is the reification of style as a flexible texture. This challenge will be addressed by pursuing three original directions in the fields of statistical learning and combinatorial optimization: 1) the formulation of Markov-based generation as a constraint problem, 2) the development of feature generation techniques for feeding machine learning algorithms and 3) the development of techniques to transform descriptors into controllers.
Two large-scale studies will be conducted with well-known creators using these Flow machines, during which the whole creation process will be recorded, stored, and analyzed, providing the first complete chronicles of professional-level artifacts. The artifacts, a music album and a novel, will be published in their respective ecosystems, and the reaction of the audience will be measured and analyzed to further assess the impact of Flow machines on creation. The technologies developed and the pilot studies will serve as pioneering experiments to turn Flow machines into a field of study and explore other domains of creation.
Max ERC Funding
2 240 120 €
Duration
Start date: 2012-08-01, End date: 2017-07-31
Project acronym MEDYMA
Project Biophysical Modeling and Analysis of Dynamic Medical Images
Researcher (PI) Nicholas Ayache
Host Institution (HI) INSTITUT NATIONAL DE RECHERCHE ENINFORMATIQUE ET AUTOMATIQUE
Call Details Advanced Grant (AdG), PE6, ERC-2011-ADG_20110209
Summary During the past decades, exceptional progress was made with in vivo medical imaging technologies to capture the anatomical, structural and physiological properties of tissues and organs in a patient, with an ever increasing spatial and temporal resolution.
The physician is now faced with a formidable overflow of information, especially when a time dimension is added to the already hard to integrate 3-D spatial, multimodal and multiscale dimensions of modern medical images. This increasingly hampers the early detection and understanding of subtle image modifications which can have a vital impact on the patient's health.
To change this situation, this proposal introduces a new generation of computational models for the simulation and analysis of dynamic medical images. Thanks to their generative nature, they will allow the construction of databases of synthetic, realistic medical image sequences simulating various evolving diseases, producing an invaluable new resource for training and benchmarking. Leveraging on their principled biophysical and statistical foundations, these new models will bring a remarkable added clinical value after they are personalized with innovative methods to fit the medical images of any specific patient.
By explicitly revealing the underlying evolving biophysical processes observable in the images, this approach will yield new groundbreaking image processing tools to correctly interpret the patient's condition (computer aided diagnosis), to accurately predict the future evolution (computer aided prognosis), and to precisely simulate and monitor an optimal and personalized therapeutic strategy (computer aided therapy). First applications will concern high impact diseases including brain tumors, Alzheimer's disease, heart failure and cardiac arrhythmia and will open new horizons in computational medical imaging.
Summary
During the past decades, exceptional progress was made with in vivo medical imaging technologies to capture the anatomical, structural and physiological properties of tissues and organs in a patient, with an ever increasing spatial and temporal resolution.
The physician is now faced with a formidable overflow of information, especially when a time dimension is added to the already hard to integrate 3-D spatial, multimodal and multiscale dimensions of modern medical images. This increasingly hampers the early detection and understanding of subtle image modifications which can have a vital impact on the patient's health.
To change this situation, this proposal introduces a new generation of computational models for the simulation and analysis of dynamic medical images. Thanks to their generative nature, they will allow the construction of databases of synthetic, realistic medical image sequences simulating various evolving diseases, producing an invaluable new resource for training and benchmarking. Leveraging on their principled biophysical and statistical foundations, these new models will bring a remarkable added clinical value after they are personalized with innovative methods to fit the medical images of any specific patient.
By explicitly revealing the underlying evolving biophysical processes observable in the images, this approach will yield new groundbreaking image processing tools to correctly interpret the patient's condition (computer aided diagnosis), to accurately predict the future evolution (computer aided prognosis), and to precisely simulate and monitor an optimal and personalized therapeutic strategy (computer aided therapy). First applications will concern high impact diseases including brain tumors, Alzheimer's disease, heart failure and cardiac arrhythmia and will open new horizons in computational medical imaging.
Max ERC Funding
2 498 327 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym MEMCAD
Project Memory Compositional Abstract Domains:
Certification of Memory Intensive Critical Softwares
Researcher (PI) Xavier Philippe Rival
Host Institution (HI) INSTITUT NATIONAL DE RECHERCHE ENINFORMATIQUE ET AUTOMATIQUE
Call Details Starting Grant (StG), PE6, ERC-2011-StG_20101014
Summary Every year, software bugs cost hundreds of millions of euros to compagnies and administrations. A number of disasters such as the Ariane 5 first flight failure can are due to faulty softwares. Static analysis aims at computing automatically properties of softwares, so as to prove they are exempt from some class of bugs. In the last ten years, static analysis of numeric intensive applications improved dramatically so that the certification of safety properties like the absence of runtime errors in industrial size control-command, numeric intensive applications, such as Airbus fly-by-wire softwares is now feasible.
By contrast, the situation is much worse for memory intensive softwares. Existing static analyzers for such softwares do not scale to large scale softwares, and fail to prove strong invariants on large classes of softwares. These limitations stem from the fact they use a monolithic algebra of logical formulas (or abstract domain).
Our proposal is based on the observation that the complex memory properties that need be reasoned about should be decomposed in combinations of simpler properties. Therefore, in static analysis, a powerful memory abstract domain could be designed by combining several simpler domains, specific to common memory usage patterns. The benefit of this novel vision is twofold: first it would make it possible to simplify drastically the design of complex abstract domains required to reason about complex softwares, hereby allowing certification of complex memory intensive softwares by automatic static analysis; second, it would enable to split down and better control the cost of the analyses, thus significantly helping scalability.
This shift of focus will bring both theoretical and practical improvements to the program certification field. We propose to build a static analysis framework for reasoning about memory properties, and put it to work on important classes of applications, including large safety critical memory intensive softwares.
Summary
Every year, software bugs cost hundreds of millions of euros to compagnies and administrations. A number of disasters such as the Ariane 5 first flight failure can are due to faulty softwares. Static analysis aims at computing automatically properties of softwares, so as to prove they are exempt from some class of bugs. In the last ten years, static analysis of numeric intensive applications improved dramatically so that the certification of safety properties like the absence of runtime errors in industrial size control-command, numeric intensive applications, such as Airbus fly-by-wire softwares is now feasible.
By contrast, the situation is much worse for memory intensive softwares. Existing static analyzers for such softwares do not scale to large scale softwares, and fail to prove strong invariants on large classes of softwares. These limitations stem from the fact they use a monolithic algebra of logical formulas (or abstract domain).
Our proposal is based on the observation that the complex memory properties that need be reasoned about should be decomposed in combinations of simpler properties. Therefore, in static analysis, a powerful memory abstract domain could be designed by combining several simpler domains, specific to common memory usage patterns. The benefit of this novel vision is twofold: first it would make it possible to simplify drastically the design of complex abstract domains required to reason about complex softwares, hereby allowing certification of complex memory intensive softwares by automatic static analysis; second, it would enable to split down and better control the cost of the analyses, thus significantly helping scalability.
This shift of focus will bring both theoretical and practical improvements to the program certification field. We propose to build a static analysis framework for reasoning about memory properties, and put it to work on important classes of applications, including large safety critical memory intensive softwares.
Max ERC Funding
1 489 663 €
Duration
Start date: 2011-10-01, End date: 2017-09-30
Project acronym MORPHODYNAMICS
Project Morphodynamics in Plants: from gene to shape
Researcher (PI) Jan Traas
Host Institution (HI) INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE
Call Details Advanced Grant (AdG), LS3, ERC-2011-ADG_20110310
Summary Morphodynamics is aimed at understanding how shape in plants is controlled during development, a major issue in developmental biology.. So far, research in the field has been mainly based on qualitative observations of mutants, with little considerations for the physics of the cells and tissues leaving many questions unanswered or unexplored. Here, using recent technological advances, to which the applicant has largely contributed, we propose an interdisciplinary and quantitative analysis of molecular and biophysical growth parameters from the cell to the organ level.
Because the mechanical properties of the cell wall are generally accepted to control local growth rates and directions, their contribution to morphogenesis will be the central focus. How the molecular regulatory networks, including cell identity genes, influence cell wall synthesis and structure to induce local growth rates and directions is largely unknown at present, mainly because our knowledge lacks integration at different levels of complexity. In addition to the quantitative and interdisciplinary character of this proposal, an original aspect of the project will address the multi-scale nature of a growing tissue, establishing a causality link between local wall properties and multi-cellular outputs.
To address this issue, we will combine cutting edge live imaging tools and micromechanical approaches with modelling frameworks recently developed in our laboratory. This will be performed using the developing flower in Arabidopsis, one of the best studied systems in biology and which has the strong advantage to grow without cell migration or rearrangement, vastly facilitating the dialog between the observations and the predictions from the models.
In summary, using different interdisciplinary concepts and methods, developed in our laboratory and coming from biology, physics and computer science, we will produce for the first time a mechanistic and multi-scale view of the growing flower bud.
Summary
Morphodynamics is aimed at understanding how shape in plants is controlled during development, a major issue in developmental biology.. So far, research in the field has been mainly based on qualitative observations of mutants, with little considerations for the physics of the cells and tissues leaving many questions unanswered or unexplored. Here, using recent technological advances, to which the applicant has largely contributed, we propose an interdisciplinary and quantitative analysis of molecular and biophysical growth parameters from the cell to the organ level.
Because the mechanical properties of the cell wall are generally accepted to control local growth rates and directions, their contribution to morphogenesis will be the central focus. How the molecular regulatory networks, including cell identity genes, influence cell wall synthesis and structure to induce local growth rates and directions is largely unknown at present, mainly because our knowledge lacks integration at different levels of complexity. In addition to the quantitative and interdisciplinary character of this proposal, an original aspect of the project will address the multi-scale nature of a growing tissue, establishing a causality link between local wall properties and multi-cellular outputs.
To address this issue, we will combine cutting edge live imaging tools and micromechanical approaches with modelling frameworks recently developed in our laboratory. This will be performed using the developing flower in Arabidopsis, one of the best studied systems in biology and which has the strong advantage to grow without cell migration or rearrangement, vastly facilitating the dialog between the observations and the predictions from the models.
In summary, using different interdisciplinary concepts and methods, developed in our laboratory and coming from biology, physics and computer science, we will produce for the first time a mechanistic and multi-scale view of the growing flower bud.
Max ERC Funding
2 368 004 €
Duration
Start date: 2012-05-01, End date: 2018-04-30
Project acronym MORPHORCE
Project The input of mechanical forces to morphogenesis and wound healing: a systematic dissection
Researcher (PI) Michel Labouesse
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), LS3, ERC-2011-ADG_20110310
Summary The importance of mechanical forces in biology is well accepted, yet an integrated view of their mode of action in vivo is lacking. We intend to characterize in-depth the physical forces and cellular processes that coordinate the morphogenesis of different cell types contributing to an organ, taking the C. elegans embryo as a paradigm.
We will achieve this by pursuing three axes:
1. Building on our discovery of a hemidesmosome-based mechanotransduction pathway that operates between contracting muscles and epidermal cells, we will combine genetic analysis with single-molecule biophysical methods to address three issues. i) What is the primary mechanosensor responding to tension within hemidesmosomes and how does it work? ii) How are all epidermal targets of muscle tension activated? iii) What is the biophysical mechanism stabilizing epidermal cells between muscle contractions?
2. We will test several features of a finite element model predicting a key role of microtubule-based epidermal stiffness and hydrostatic pressure in elongation. We will combine quantitative mechanical measures with force biosensors and laser ablation to define how these resistive forces contribute to embryo elongation along the anterior-posterior axis.
3. To extend our conclusions to the medical field, we will knockdown homologues of proteins identified in C. elegans, as well as proteins of the same families, in keratinocytes with partially damaged hemidesmosomes. Cells will be submitted to wound assays or grown on a stretchable substrate. Positive hits will be further characterized and tested in mouse models with partially defective hemidesmosomes.
We foresee that this project will identify conserved proteins and processes relaying mechanical forces, and thus shed light on the mechanical basis of morphogenesis. We also expect our work to have strong impact in medicine, since the outcome of many pathologies, including wound healing and cancer, is thought to be strongly influenced by forces.
Summary
The importance of mechanical forces in biology is well accepted, yet an integrated view of their mode of action in vivo is lacking. We intend to characterize in-depth the physical forces and cellular processes that coordinate the morphogenesis of different cell types contributing to an organ, taking the C. elegans embryo as a paradigm.
We will achieve this by pursuing three axes:
1. Building on our discovery of a hemidesmosome-based mechanotransduction pathway that operates between contracting muscles and epidermal cells, we will combine genetic analysis with single-molecule biophysical methods to address three issues. i) What is the primary mechanosensor responding to tension within hemidesmosomes and how does it work? ii) How are all epidermal targets of muscle tension activated? iii) What is the biophysical mechanism stabilizing epidermal cells between muscle contractions?
2. We will test several features of a finite element model predicting a key role of microtubule-based epidermal stiffness and hydrostatic pressure in elongation. We will combine quantitative mechanical measures with force biosensors and laser ablation to define how these resistive forces contribute to embryo elongation along the anterior-posterior axis.
3. To extend our conclusions to the medical field, we will knockdown homologues of proteins identified in C. elegans, as well as proteins of the same families, in keratinocytes with partially damaged hemidesmosomes. Cells will be submitted to wound assays or grown on a stretchable substrate. Positive hits will be further characterized and tested in mouse models with partially defective hemidesmosomes.
We foresee that this project will identify conserved proteins and processes relaying mechanical forces, and thus shed light on the mechanical basis of morphogenesis. We also expect our work to have strong impact in medicine, since the outcome of many pathologies, including wound healing and cancer, is thought to be strongly influenced by forces.
Max ERC Funding
2 495 504 €
Duration
Start date: 2012-05-01, End date: 2018-04-30