Project acronym BIOMOLECULAR_COMP
Project Biomolecular computers
Researcher (PI) Ehud Shapiro
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS9, ERC-2008-AdG
Summary Autonomous programmable computing devices made of biological molecules hold the promise of interacting with the biological environment in future biological and medical applications. Our laboratory's long-term objective is to develop a 'Doctor in a cell': molecular-sized device that can roam the body, equipped with medical knowledge. It would diagnose a disease by analyzing the data available in its biochemical environment based on the encoded medical knowledge and treat it by releasing the appropriate drug molecule in situ. This kind of device might, in the future, be delivered to all cells in a specific tissue, organ or the whole organism, and cure or kill only those cells diagnosed with a disease. Our laboratory embarked on the attempt to design and build these molecular computing devices and lay the foundation for their future biomedical applications. Several important milestones have already been accomplished towards the realization of the Doctor in a cell vision. The subject of this proposal is a construction of autonomous biomolecular computers that could be delivered into a living cell, interact with endogenous biomolecules that are known to indicate diseases, logically analyze them, make a diagnostic decision and couple it to the production of an active biomolecule capable of influencing cell fate.
Summary
Autonomous programmable computing devices made of biological molecules hold the promise of interacting with the biological environment in future biological and medical applications. Our laboratory's long-term objective is to develop a 'Doctor in a cell': molecular-sized device that can roam the body, equipped with medical knowledge. It would diagnose a disease by analyzing the data available in its biochemical environment based on the encoded medical knowledge and treat it by releasing the appropriate drug molecule in situ. This kind of device might, in the future, be delivered to all cells in a specific tissue, organ or the whole organism, and cure or kill only those cells diagnosed with a disease. Our laboratory embarked on the attempt to design and build these molecular computing devices and lay the foundation for their future biomedical applications. Several important milestones have already been accomplished towards the realization of the Doctor in a cell vision. The subject of this proposal is a construction of autonomous biomolecular computers that could be delivered into a living cell, interact with endogenous biomolecules that are known to indicate diseases, logically analyze them, make a diagnostic decision and couple it to the production of an active biomolecule capable of influencing cell fate.
Max ERC Funding
2 125 980 €
Duration
Start date: 2009-01-01, End date: 2013-10-31
Project acronym CIRCUIT
Project Neural circuits for space representation in the mammalian cortex
Researcher (PI) Edvard Ingjald Moser
Host Institution (HI) NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Call Details Advanced Grant (AdG), LS5, ERC-2008-AdG
Summary Neuroscience is one of the fastest-developing areas of science, but it is fair to say that we are still far from understanding how the brain produces subjective experience. For example, simple questions about the origin of thought, imagination, social interaction, or feelings lack even rudimentary answers. We have learnt much about the workings of individual cells and synapses, but psychological phenomena cannot be understood only at this level. These phenomena all emerge from interactions between large numbers of diverse cells in intermingled neural circuits. A major obstacle has been the absence of concepts and tools for investigating neural computation at the circuit level. The aim of this proposal is to combine new transgenic methods for cell type-specific intervention with large-scale multisite single-cell recording to determine how a basic cognitive function self-localization is generated in a functionally well-described mammalian neural circuit. We shall use our recent discovery of entorhinal grid cells as an access ramp. Grid cells fire only when the animal moves through certain locations. For each cell, these locations define a periodic triangular array spanning the whole environment. Grid cells co-exist with other entorhinal cell types encoding head direction, geometric borders, or conjunctions of features. This network is thought to form an essential part of the brain s coordinate system for metric navigation but the detailed wiring, the mechanism of grid formation, and the function of each morphological and functional cell type all remain to be determined. We shall address these open questions by measuring how dynamic spatial representation is affected by transgene-induced activation or inactivation of the individual components of the circuit. The endeavour will pioneer the functional analysis of neural circuits and may, perhaps for the first time, provide us with mechanistic insight into a non-sensory cognitive function in the mammalian cortex.
Summary
Neuroscience is one of the fastest-developing areas of science, but it is fair to say that we are still far from understanding how the brain produces subjective experience. For example, simple questions about the origin of thought, imagination, social interaction, or feelings lack even rudimentary answers. We have learnt much about the workings of individual cells and synapses, but psychological phenomena cannot be understood only at this level. These phenomena all emerge from interactions between large numbers of diverse cells in intermingled neural circuits. A major obstacle has been the absence of concepts and tools for investigating neural computation at the circuit level. The aim of this proposal is to combine new transgenic methods for cell type-specific intervention with large-scale multisite single-cell recording to determine how a basic cognitive function self-localization is generated in a functionally well-described mammalian neural circuit. We shall use our recent discovery of entorhinal grid cells as an access ramp. Grid cells fire only when the animal moves through certain locations. For each cell, these locations define a periodic triangular array spanning the whole environment. Grid cells co-exist with other entorhinal cell types encoding head direction, geometric borders, or conjunctions of features. This network is thought to form an essential part of the brain s coordinate system for metric navigation but the detailed wiring, the mechanism of grid formation, and the function of each morphological and functional cell type all remain to be determined. We shall address these open questions by measuring how dynamic spatial representation is affected by transgene-induced activation or inactivation of the individual components of the circuit. The endeavour will pioneer the functional analysis of neural circuits and may, perhaps for the first time, provide us with mechanistic insight into a non-sensory cognitive function in the mammalian cortex.
Max ERC Funding
2 499 112 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym IMAGO
Project Imaging regulatory pathways of angiogenesis
Researcher (PI) Michal Neeman
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS7, ERC-2008-AdG
Summary Homeostasis of multicellular tissues relies on accurate match of vascular supply and drain to the needs of the tissue. Multiple pathways are involved in detection, signalling and execution of the required steps involved in organization of blood and lymphatic vessels during embryonic development. Similar mechanisms are utilized for overcoming changes in tissue requirements also in adult tissues and in pathological processes. The goal of this work is to reveal the dynamic forces that shape the blood vessels during angiogenesis. In particular, we would like to explore the impact of interstitial convective flow in dynamic imprinting of growth factor signalling, thereby regulating vascular patterning. Angiogenesis is explored here as an example for a possible general role for interstitial convection of growth factors in determination of the fine spatial patterning of tissue morphogenesis in vertebrates. To achieve this goal, we will develop multi-modality tools for imaging the regulation of vascular patterning. In vivo imaging will then be utilized for mapping vascular patterning in pathological and physiological angiogenesis including tumours, wound repair, the preovulatory ovarian follicle and foetal implantation sites. Whole body optical, CT, ultrasound and MRI will be applied for non-invasive imaging of deep organs. Microscopic morphometric and molecular information will be derived from the macroscopic imaging data, using selective molecular imaging approaches and functional imaging tools with specific pharmacological models that will be developed to account for interstitial convective flow. Intravital two photon microscopy and fluorescence endoscopy will be used for high resolution evaluation of vascular patterning. The evaluation of novel mechanisms for spatial regulation of intercellular growth factor signalling, will allow us to define new potential targets for intervention, and to develop new tools for preclinical and clinical imaging of angiogenesis.
Summary
Homeostasis of multicellular tissues relies on accurate match of vascular supply and drain to the needs of the tissue. Multiple pathways are involved in detection, signalling and execution of the required steps involved in organization of blood and lymphatic vessels during embryonic development. Similar mechanisms are utilized for overcoming changes in tissue requirements also in adult tissues and in pathological processes. The goal of this work is to reveal the dynamic forces that shape the blood vessels during angiogenesis. In particular, we would like to explore the impact of interstitial convective flow in dynamic imprinting of growth factor signalling, thereby regulating vascular patterning. Angiogenesis is explored here as an example for a possible general role for interstitial convection of growth factors in determination of the fine spatial patterning of tissue morphogenesis in vertebrates. To achieve this goal, we will develop multi-modality tools for imaging the regulation of vascular patterning. In vivo imaging will then be utilized for mapping vascular patterning in pathological and physiological angiogenesis including tumours, wound repair, the preovulatory ovarian follicle and foetal implantation sites. Whole body optical, CT, ultrasound and MRI will be applied for non-invasive imaging of deep organs. Microscopic morphometric and molecular information will be derived from the macroscopic imaging data, using selective molecular imaging approaches and functional imaging tools with specific pharmacological models that will be developed to account for interstitial convective flow. Intravital two photon microscopy and fluorescence endoscopy will be used for high resolution evaluation of vascular patterning. The evaluation of novel mechanisms for spatial regulation of intercellular growth factor signalling, will allow us to define new potential targets for intervention, and to develop new tools for preclinical and clinical imaging of angiogenesis.
Max ERC Funding
2 278 344 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym IMMUNE/MEMORY AGING
Project Can immune system rejuvenation restore age-related memory loss?
Researcher (PI) Michal Eisenbach-Schwartz
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS5, ERC-2008-AdG
Summary With increased life expectancy, there has been a critical growth in the portion of the population that suffers from age-related cognitive decline and dementia. Attempts are therefore being made to find ways to slow brain-aging processes; successful therapies would have a significant impact on the quality of life of individuals, and decrease healthcare expenditures. Aging of the immune system has never been suggested as a factor in memory loss. My group formulated the concept of protective autoimmunity , suggesting a linkage between immunity and self-maintenance in the context of the brain in health and disease. Recently, we showed that T lymphocytes recognizing brain-self antigens have a pivotal role in maintaining hippocampal plasticity, as manifested by reduced neurogenesis and impaired cognitive abilities in T-cell deficient mice. Taken together, our novel observations that T cell immunity contributes to hippocampal plasticity, and the fact that T cell immunity decreases with progressive aging create the basis for the present proposal. We will focus on the following questions: (a) Which aspects of cognition are supported by the immune system- learning, memory or both; (b) whether aging of the immune system is sufficient to induce aging of the brain; (c) whether activation of the immune system is sufficient to reverse age-related cognitive decline; (d) the mechanism underlying the effect of peripheral immunity on brain cognition; and (e) potential therapeutic implications of our findings. Our preliminary results demonstrate that the immune system contributes to spatial memory, and that imposing an immune deficiency is sufficient to cause a reversible memory deficit. These findings give strong reason for optimism that memory loss in the elderly is preventable and perhaps reversible by immune-based therapies; we hope that, in the not too distant future, our studies will enable development of a vaccine to prevent CNS aging and cognitive loss in elderly.
Summary
With increased life expectancy, there has been a critical growth in the portion of the population that suffers from age-related cognitive decline and dementia. Attempts are therefore being made to find ways to slow brain-aging processes; successful therapies would have a significant impact on the quality of life of individuals, and decrease healthcare expenditures. Aging of the immune system has never been suggested as a factor in memory loss. My group formulated the concept of protective autoimmunity , suggesting a linkage between immunity and self-maintenance in the context of the brain in health and disease. Recently, we showed that T lymphocytes recognizing brain-self antigens have a pivotal role in maintaining hippocampal plasticity, as manifested by reduced neurogenesis and impaired cognitive abilities in T-cell deficient mice. Taken together, our novel observations that T cell immunity contributes to hippocampal plasticity, and the fact that T cell immunity decreases with progressive aging create the basis for the present proposal. We will focus on the following questions: (a) Which aspects of cognition are supported by the immune system- learning, memory or both; (b) whether aging of the immune system is sufficient to induce aging of the brain; (c) whether activation of the immune system is sufficient to reverse age-related cognitive decline; (d) the mechanism underlying the effect of peripheral immunity on brain cognition; and (e) potential therapeutic implications of our findings. Our preliminary results demonstrate that the immune system contributes to spatial memory, and that imposing an immune deficiency is sufficient to cause a reversible memory deficit. These findings give strong reason for optimism that memory loss in the elderly is preventable and perhaps reversible by immune-based therapies; we hope that, in the not too distant future, our studies will enable development of a vaccine to prevent CNS aging and cognitive loss in elderly.
Max ERC Funding
1 650 000 €
Duration
Start date: 2009-01-01, End date: 2012-12-31
Project acronym PI3K-III COMPLEX
Project The PI3K-III complex: Function in cell regulation and tumour suppression
Researcher (PI) Harald Alfred Stenmark
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Advanced Grant (AdG), LS3, ERC-2008-AdG
Summary Phosphoinositides (PIs), phosphorylated derivatives of phosphatidylinositol (PtdIns), control cellular functions through recruitment of cytosolic proteins to specific membranes. Among the kinases involved in PI generation, the PI3K-III complex, which catalyzes conversion of PtdIns into PtdIns 3-phosphate (PI3P), is of great interest for several reasons. Firstly, it is required for three topologically related membrane involution processes - the biogenesis of multivesicular endosomes, autophagy, and cytokinesis. Secondly, through its catalytic product this protein complex mediates anti-apoptotic and antiproliferative signalling. Thirdly, several subunits of the PI3K-III complex are known tumour suppressors, making the PI3K-III complex a possible target for cancer therapy and diagnostics. This proposal aims to undertake a systematic analysis of the PI3K-III complex and its functions, and the following key questions will be addressed: How is the PI3K-III complex recruited to specific membranes? How does it control membrane involution and signal transduction? By which mechanisms do subunits of this protein complex serve as tumour suppressors? The project will be divided into seven subprojects, which include (1) characterization of the PI3K-III complex, (2) detection of the PI3K-III product PI3P in cells and tissues, (3) the function of the PI3K-III complex in downregulation of growth factor receptors, (4) the function of the PI3K-III complex in autophagy, (5) the function of the PI3K-III complex in cytokinesis, (6) the function of the PI3K-III complex in cell signalling, and (7) dissecting the tumour suppressor activities of the PI3K-III complex. The analyses will range from protein biochemistry to development of novel imaging probes, siRNA screens for novel PI3P effectors, functional characterization of PI3K-III subunits and PI3P effectors in cell culture models, and tumour suppressor analyses in novel Drosophila models.
Summary
Phosphoinositides (PIs), phosphorylated derivatives of phosphatidylinositol (PtdIns), control cellular functions through recruitment of cytosolic proteins to specific membranes. Among the kinases involved in PI generation, the PI3K-III complex, which catalyzes conversion of PtdIns into PtdIns 3-phosphate (PI3P), is of great interest for several reasons. Firstly, it is required for three topologically related membrane involution processes - the biogenesis of multivesicular endosomes, autophagy, and cytokinesis. Secondly, through its catalytic product this protein complex mediates anti-apoptotic and antiproliferative signalling. Thirdly, several subunits of the PI3K-III complex are known tumour suppressors, making the PI3K-III complex a possible target for cancer therapy and diagnostics. This proposal aims to undertake a systematic analysis of the PI3K-III complex and its functions, and the following key questions will be addressed: How is the PI3K-III complex recruited to specific membranes? How does it control membrane involution and signal transduction? By which mechanisms do subunits of this protein complex serve as tumour suppressors? The project will be divided into seven subprojects, which include (1) characterization of the PI3K-III complex, (2) detection of the PI3K-III product PI3P in cells and tissues, (3) the function of the PI3K-III complex in downregulation of growth factor receptors, (4) the function of the PI3K-III complex in autophagy, (5) the function of the PI3K-III complex in cytokinesis, (6) the function of the PI3K-III complex in cell signalling, and (7) dissecting the tumour suppressor activities of the PI3K-III complex. The analyses will range from protein biochemistry to development of novel imaging probes, siRNA screens for novel PI3P effectors, functional characterization of PI3K-III subunits and PI3P effectors in cell culture models, and tumour suppressor analyses in novel Drosophila models.
Max ERC Funding
2 272 000 €
Duration
Start date: 2010-01-01, End date: 2014-12-31
Project acronym REGULATORYCIRCUITS
Project Novel Systematic Strategies for Elucidating Cellular Regulatory Circuits
Researcher (PI) Nir Friedman
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Advanced Grant (AdG), LS2, ERC-2008-AdG
Summary The precise regulation of gene expression has been the subject of extensive scrutiny. Nonetheless, there is a big gap between genomic characterization of transcriptional responses and our predictions based on known molecular mechanisms and networks and of transcription regulation. In this proposal I argue for an approach to bridge this gap by using a novel experimental strategy that exploits the recent maturation of two technologies: the use of fluorescence reporter techniques to monitor promoter activity and high-throughput genetic manipulations for the construction of combinatorial genetic perturbations. By combining these, we will screen for genes that modulate the transcriptional response of target promoters, use genetic interactions between them to better resolve their functional dependencies, and build detailed quantitative models of transcriptional processes. We will use the budding yeast model organism, which allows for efficient manipulations, to dissect two transcriptional responses that are prototypical of many regulatory networks in living cells: [1] The early response to osmotic stress, which is mediated by at least two signaling pathways and multiple transcription factors, and [2] the central carbon metabolism response to shifts in carbon source, which involves multiple sensing and signaling pathways to maintain homeostasis. Our approach will elucidate mechanisms that are opaque to classical screens and facilitate building detailed predictive models of these responses. These results will lead to understanding of general principles that govern transcriptional networks. This is the first approach to comprehensively characterize the molecular mechanisms that modulate a transcriptional response, and arrange them in a coherent network. It will open many questions for detailed biochemical investigations, as well as set the stage to extend these ideas to use more detailed phenotypic assays and in more complex organisms.
Summary
The precise regulation of gene expression has been the subject of extensive scrutiny. Nonetheless, there is a big gap between genomic characterization of transcriptional responses and our predictions based on known molecular mechanisms and networks and of transcription regulation. In this proposal I argue for an approach to bridge this gap by using a novel experimental strategy that exploits the recent maturation of two technologies: the use of fluorescence reporter techniques to monitor promoter activity and high-throughput genetic manipulations for the construction of combinatorial genetic perturbations. By combining these, we will screen for genes that modulate the transcriptional response of target promoters, use genetic interactions between them to better resolve their functional dependencies, and build detailed quantitative models of transcriptional processes. We will use the budding yeast model organism, which allows for efficient manipulations, to dissect two transcriptional responses that are prototypical of many regulatory networks in living cells: [1] The early response to osmotic stress, which is mediated by at least two signaling pathways and multiple transcription factors, and [2] the central carbon metabolism response to shifts in carbon source, which involves multiple sensing and signaling pathways to maintain homeostasis. Our approach will elucidate mechanisms that are opaque to classical screens and facilitate building detailed predictive models of these responses. These results will lead to understanding of general principles that govern transcriptional networks. This is the first approach to comprehensively characterize the molecular mechanisms that modulate a transcriptional response, and arrange them in a coherent network. It will open many questions for detailed biochemical investigations, as well as set the stage to extend these ideas to use more detailed phenotypic assays and in more complex organisms.
Max ERC Funding
2 199 899 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym TICE
Project TRANSCRIPTOMICS IN CANCER EPIDEMIOLOGY
Researcher (PI) Eiliv Lund
Host Institution (HI) UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET
Call Details Advanced Grant (AdG), LS7, ERC-2008-AdG
Summary NOWAC is the first prospective study with a globolomic design. This is an extension of the current cohort study with its questionnaire information and biological material for analysis of biomarkers, proteomics and single nucleotide polymorphisms (SNPs). The design of NOWAC adds biological material for analysis of the transcriptome in prospectively collected buffered peripheral blood samples, the postgenome biobank. Further, both peripheral blood and tumor tissue are collected from breast cancer patients diagnosed within the cohort together with matched controls. The latter biological material gives a new multidimensional design with a unique biological material at the end-point. The transcriptomic analysis will include both mRNA and miRNA as new technology (microarray and massive parallel sequencing) allows large scale studies. miRNAs could be promising markers for pathways analysis related to the carcinogenic process and for diagnosis and screening tests of breast cancer. These high-troughput technologies have analyses challenges both in bioinformatics and biostatistics therefore success depends on the development of new analytical strategies.This novel design is the observational counterpart to systems biology, or systems epidemiology. Systems epidemiology will seek to understand biological processes by integrating observational derived pathways information into the current prospective design. A true interdisciplinary approach has been implemented. The upside is the potential for an improved understanding of causality in epidemiology by opening up for quantification of traditional criteria of biological plausibility in a more complete biological model. The postgenome biobank with 50 000 participants out of the 172 000 participants in NOWAC and its unique national design and richness of biological material makes it a very strong case for interdisciplinary collaboration based on a population-based study representative of the real and complex lifestyle environment.
Summary
NOWAC is the first prospective study with a globolomic design. This is an extension of the current cohort study with its questionnaire information and biological material for analysis of biomarkers, proteomics and single nucleotide polymorphisms (SNPs). The design of NOWAC adds biological material for analysis of the transcriptome in prospectively collected buffered peripheral blood samples, the postgenome biobank. Further, both peripheral blood and tumor tissue are collected from breast cancer patients diagnosed within the cohort together with matched controls. The latter biological material gives a new multidimensional design with a unique biological material at the end-point. The transcriptomic analysis will include both mRNA and miRNA as new technology (microarray and massive parallel sequencing) allows large scale studies. miRNAs could be promising markers for pathways analysis related to the carcinogenic process and for diagnosis and screening tests of breast cancer. These high-troughput technologies have analyses challenges both in bioinformatics and biostatistics therefore success depends on the development of new analytical strategies.This novel design is the observational counterpart to systems biology, or systems epidemiology. Systems epidemiology will seek to understand biological processes by integrating observational derived pathways information into the current prospective design. A true interdisciplinary approach has been implemented. The upside is the potential for an improved understanding of causality in epidemiology by opening up for quantification of traditional criteria of biological plausibility in a more complete biological model. The postgenome biobank with 50 000 participants out of the 172 000 participants in NOWAC and its unique national design and richness of biological material makes it a very strong case for interdisciplinary collaboration based on a population-based study representative of the real and complex lifestyle environment.
Max ERC Funding
2 300 000 €
Duration
Start date: 2009-01-01, End date: 2014-06-30
Project acronym VARB
Project Variability and Robustness in Bio-molecular systems
Researcher (PI) Naama Barkai
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS2, ERC-2008-AdG
Summary Cells process information using biochemical networks of interacting proteins and genes. We wish to understand the principles that guide the design of such networks. In particular, we are interested in the interplay between variability, inherent to biological systems, and the precision of cellular computing. To better understand this interplay, we will: (1) Characterize the extent of gene expression variability and define its genetic determinants, (2) Reveal how variability is buffered and (3) Describe instances where variability (or 'noise') is an integral part of cellular computation. The study will be conducted in the multidisciplinary atmosphere of our lab, by students trained in physics, computer science, chemistry and biology. Specific issues include: 1. Gene expression variability: we will focus on the influence of chromatin structure on gene expression variability, as suggested by our bioinformatics analysis. 2. Robustness and scaling in embryonic patterning: We will study the means by which fluctuations are buffered during the development of multicellular organisms. We will focus on the robustness of morphogen gradients to protein levels, and on the ability to maintain proportionate pattern in tissues of different size. 3. Noise-driven transitions in a fluctuating environment: Our preliminary results suggest that noise plays an integral part in phosphate homeostasis in S. cerevisiae. We will characterize the role of noise in this system and study its evolutionary implications. Together, our study will shed light on one we believe to be the fundamental challenge of biological information processing: ensuring a reliable and reproducible function in the highly variable biological environment. Our study will furthermore define novel multidisciplinary, system-level paradigms and approaches that will guide further studies of bio-molecular systems
Summary
Cells process information using biochemical networks of interacting proteins and genes. We wish to understand the principles that guide the design of such networks. In particular, we are interested in the interplay between variability, inherent to biological systems, and the precision of cellular computing. To better understand this interplay, we will: (1) Characterize the extent of gene expression variability and define its genetic determinants, (2) Reveal how variability is buffered and (3) Describe instances where variability (or 'noise') is an integral part of cellular computation. The study will be conducted in the multidisciplinary atmosphere of our lab, by students trained in physics, computer science, chemistry and biology. Specific issues include: 1. Gene expression variability: we will focus on the influence of chromatin structure on gene expression variability, as suggested by our bioinformatics analysis. 2. Robustness and scaling in embryonic patterning: We will study the means by which fluctuations are buffered during the development of multicellular organisms. We will focus on the robustness of morphogen gradients to protein levels, and on the ability to maintain proportionate pattern in tissues of different size. 3. Noise-driven transitions in a fluctuating environment: Our preliminary results suggest that noise plays an integral part in phosphate homeostasis in S. cerevisiae. We will characterize the role of noise in this system and study its evolutionary implications. Together, our study will shed light on one we believe to be the fundamental challenge of biological information processing: ensuring a reliable and reproducible function in the highly variable biological environment. Our study will furthermore define novel multidisciplinary, system-level paradigms and approaches that will guide further studies of bio-molecular systems
Max ERC Funding
2 200 000 €
Duration
Start date: 2009-01-01, End date: 2013-10-31
